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Objective: A selective rise in hypothalamic lipid metabolism and the subsequent activation of SUR1/Kir6.2 ATP-sensitive K(+) (K(ATP)) channels inhibit hepatic glucose production. The mechanisms that link the ability of hypothalamic lipid metabolism to the activation of K(ATP) channels remain unknown., Research Design and Methods: To examine whether hypothalamic protein kinase C (PKC) mediates the ability of central nervous system lipids to activate K(ATP) channels and regulate glucose production in normal rodents, we first activated hypothalamic PKC in the absence or presence of K(ATP) channel inhibition. We then inhibited hypothalamic PKC in the presence of lipids. Tracer-dilution methodology in combination with the pancreatic clamp technique was used to assess the effect of hypothalamic administrations on glucose metabolism in vivo., Results: We first reported that direct activation of hypothalamic PKC via direct hypothalamic delivery of PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) suppressed glucose production. Coadministration of hypothalamic PKC-delta inhibitor rottlerin with OAG prevented the ability of OAG to activate PKC-delta and lower glucose production. Furthermore, hypothalamic dominant-negative Kir6.2 expression or the delivery of the K(ATP) channel blocker glibenclamide abolished the glucose production-lowering effects of OAG. Finally, inhibition of hypothalamic PKC eliminated the ability of lipids to lower glucose production., Conclusions: These studies indicate that hypothalamic PKC activation is sufficient and necessary for lowering glucose production.

We examined the effect of docosahexaenoic acid (DHA)-enriched structured lipids-diacylglycerol (SL-DG), which were synthesized using soybean oil (SO) and algae oil (AO), on hepatic lipid metabolism and the mRNA expression of genes involved in hepatic steatosis of C57BL/6J-Lep(ob/ob) compared to the SL-triacylglycerol (TG). The animals were fed a high-fat (10% lard and 10% test oils) and high-cholesterol (0.2% cholesterol) diet for 12 weeks. Mice fed SL-DG showed a lower total white adipose tissue weight and plasma triglyceride concentration than the SO group. Reduction of hepatic triglyceride content in the SL-DG group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis along with fecal triglyceride excretion compared to the SL-TG. SL-DG also lowered hepatic cholesterol levels by suppressing cholesterol regulating enzyme activity compared to the SO group. Moreover, SL-DG lowered the mRNA expressions of sterol regulatory element binding protein-1 and its target genes than TG-form oils (SO, AO and SL-TG) in the liver. Thus, the current results suggest that DHA-enriched SL-DG oil used in this study is beneficial for ameliorating hepatic steatosis in obese animal model by improving hepatic fatty acid and cholesterol metabolic enzyme activity and their gene expression.

Several studies in animals and humans have reported beneficial effects of diacylglycerol (DAG) on lipid and energy metabolism. We assessed the effect of DAG versus triacylglycerol (TAG) treatment on total energy expenditure (TEE), total fat oxidation (Fox) and respiratory quotient (RQ), and measured the oxidation rate of each oil using a respiratory chamber and the 13C-stable isotope. Eleven healthy subjects participated in a double-blind, randomized crossover study. Subjects consumed an energy maintenance diet consisting of 55% of total calories from carbohydrate, 15% from protein and 30% from fat during both the 3-day pre-chamber and 36-h chamber period. Fifty percent of the fat was test oil, containing either DAG oil or TAG oil. The oxidation rate of ingested test oils was determined by monitoring 13CO2 excretion in the breath from 13C-labeled diolein or 13C-labeled triolein. There were no significant differences in TEE, RQ and total Fox between the DAG and TAG treatment in the overall analysis. In the subgroup analysis, DAG treatment decreased RQ significantly in subjects with a high fat ratio (HFR) compared to TAG treatment. In addition, ingested diolein oxidation in DAG treatment was significantly faster than triolein oxidation in TAG treatment in the HFR group. Enhanced fat utilization with DAG treatment and rapid oxidation of ingested DAG may, at least in part, explain the greater loss of body weight and body fat related to DAG consumption found in the weight-loss studies.

This study examines the effect of diacylglycerol (DAG) oil consisting mainly of 1,3-species on fat oxidation as a possible mechanism for anti-obesity. We examined the following: (1) the long-term (23-week) effects of a DAG oil diet on the development of obesity; (2) the effect of a single ingestion of DAG oil on fat oxidation; and, (3) the short-term (2-week) effect of a DAG oil diet on fat metabolism in rats. Rats fed a DAG oil diet accumulated significantly less body fat compared to rats fed a triacylglycerol (TAG) oil diet, each oil possesses a similar fatty acid composition. More( 14)C-CO(2) was expired and less( 14)C-radioactivity was incorporated into visceral fat after administration of a tracer emulsion containing 1,3-[oleoyl-1-(14)C] diolein compared to [carboxyl-(14)C] triolein. Indirect calorimetry showed respiratory quotients were significantly lower in the DAG oil diet group than in the TAG oil diet group. More( 14)C-CO(2) was expired and less (14)C-radioactivity was incorporated into visceral fat in the DAG oil diet group than in the TAG oil diet group after a single intragastric administration of [carboxyl-(14)C] triolein. These results suggest the following. (1) DAG oil has an inhibitory effect on diet-induced fat accumulation. (2) 1,3-DAG, a major component of DAG oil, is more susceptible to oxidation. (3) A short-term ingestion of DAG oil increases fat utilization at the whole body level and results in increased oxidation of dietary fat. The stimulated fat oxidation might be one explanation for the anti-obesity effect of long-term DAG oil ingestion.

Background & Aims: Diacylglycerol oil has been shown to lower postprandial and fasting serum triacylglycerol levels and reduce body fat. The aim of this study was to investigate the effect of diacylglycerol oil on risk factors of type 2 diabetes mellitus (DM) and cardiovascular disease in type 2 DM patients., Methods: This was a double-blind controlled parallel study with 127 type 2 DM patients (aged 40-65) recruited in Hangzhou, China. All subjects consumed triacylglycerol oil in the lead-in period (14 days), then they were randomly divided into two groups and consumed diacylglycerol or triacylglycerol oil with a similar fatty acid composition (25 g/day) for 120 days. Blood samples were collected on days 0, 60 and 120 and risk factors of type 2 DM and cardiovascular disease and biochemical parameters were measured by standard methods., Results: There were a total of 112 subjects who completed the study. Diet intake did not differ significantly between groups. Body weight, BMI, waist circumference, HOMA-IR, serum insulin and leptin levels were significantly reduced from baseline in the diacylglycerol oil group but not in the triacylglycerol oil group. Serum glucose was also significantly improved in patients with higher glucose levels at baseline (>7.00 mmol/L) in the diacylglycerol oil group. Parameters of liver and kidney functions and essential fatty acids in serum phospholipids did not differ between groups., Conclusions: Diacylglycerol oil consumption improved biomarkers and anthropometric parameters of type 2 DM compared with triacylglycerol oil. No adverse reactions were observed with diacylglycerol oil consumption for type 2 DM patients. Diacylglycerol oil has an equivalent bioavailability as triacylglycerol oil in relation to providing essential fatty acids.

Postprandial hypertriglyceridemia is common in individuals with insulin resistance, and diets enriched in 1,3-diacylglycerol (DAG) may reduce postprandial plasma triglycerides (PPTGs). We enrolled 25 insulin-resistant, nondiabetic individuals in a double-blind, randomized crossover trial to test the acute and chronic effects of a DAG-enriched diet on PPTG. Participants received either DAG or triacylglycerol (TAG) oil, in food products, for 5 weeks. Fasting lipids, and two separate postprandial tests, one with DAG oil and one with TAG oil, were performed at the end of each 5 week diet period. We found no acute or chronic effects of DAG oil on PPTG. Thus, neither the DAG oil PPTG (h/mg/dl) on a chronic TAG diet [area under the curve (AUC) = 503 +/- 439] nor the TAG oil PPTG on a chronic DAG diet (AUC = 517 +/- 638) was different from the TAG oil PPTG on a chronic TAG diet (AUC = 565 +/- 362). Five weeks of a DAG-enriched diet had no acute or chronic effects on PPTG in insulin-resistant individuals. We suggest further studies to evaluate the effects of DAG on individuals with low and high TG levels.

Objective: The objective of this study was to investigate the effect of 1-year ad libitum consumption of diacylglycerol oil on body weight and serum triglyceride in Japanese men and women. DESIGN/SUBJECTS/INTERVENTION: In a 1-year double-blind, placebo-controlled parallel trial with clinic visits at month 0, 3, 6, 9, and 12, a total of 312 Japanese men (n=174) and women (n=138) (aged 22 to 73 years) with body mass index (calculated as kg/m(2)) > or =25 and/or fasting serum triglyceride level > or =150 mg/dL (1.70 mmol/L) (aged 22 to 73 years) were randomly assigned to the diacylglycerol (n=155) or triacylglycerol (n=157) group. Participants substituted their usual home cooking oil with the assigned test oils., Main Outcome Measures: Changes in anthropometrics and serum triglyceride level were monitored at 3-month intervals across a 12-month period., Results: In the intention-to-treat analysis, body weight decreased significantly in the diacylglycerol group when compared to the triacylglycerol group (P=0.013). Changes in body weight and body mass index during the study period differed between the two groups by 0.87 kg (P=0.002) and 0.32 kg (P=0.002), respectively. Participants with higher initial body mass index or greater percentage of total fat intake as diacylglycerol exhibited greater reduction in body weight. Total energy intake and physical activity were not significantly different between the groups during the study. Serum triglyceride levels decreased significantly from values in individuals with hypertriglyceridemia, but did not differ between groups., Conclusions: Modest body weight reduction was observed after 1-year ad libitum consumption of diacylglycerol oil as part of a regular diet in comparison to that of triacylglycerol oil; weight loss was greatest in participants who were obese at baseline. The weight reduction observed in diacylglycerol group was attributed to the substitution of usual home cooking oil with diacylglycerol, because total energy intake and physical activity did not differ between groups.

To investigate the effect of dietary 1,3-diacylglycerol (DAG) on the development of insulin resistance (IR) and obesity, brown adipose tissue-deficient mice, a model of high-fat diet-induced IR and obesity, were fed Western-type diets (WTD) containing either DAG oil (n = 8) or standard triacylglycerol (TAG) oil (n = 9) for 15 weeks, beginning at 8 weeks of age. Although brown adipose tissue-deficient mice became obese on both TAG- and DAG-enriched WTD (TAG-WTD and DAG-WTD), the mice eating DAG-WTD gained less weight and had less body fat accumulation. The results of glucose tolerance tests conducted after 5 weeks of each WTD were not different. However, after 10 weeks of each WTD, impaired glucose tolerance developed in the TAG-WTD group but was prevented by DAG-WTD. Exploratory analyses of gene expression suggested that consumption of DAG-WTD was associated with reduced phosphoenolpyruvate carboxykinase gene expression in liver and increased expression of the genes for peroxisome proliferator-activated receptor alpha, lipoprotein lipase, and uncoupling proteins 2 and 3 in skeletal muscle. There were no effects of the DAG-WTD on fasting and postprandial plasma triglyceride (TG) levels, hepatic TG content, or the rate of secretion of TG from the liver. These findings suggest that diets enriched in 1,3-DAG oil may reduce WTD-induced IR and body fat accumulation by suppressing gluconeogenesis in liver and stimulating fat oxidation in skeletal muscle.

Plant sterols (PS) and MUFA are well-documented cholesterol lowering agents. We aimed to determine the effect of PS esterified to olive oil fatty acids (PS-OO) on blood lipid profile and lipid peroxidation in hypercholesterolaemic subjects. Twenty-one moderately overweight, hypercholesterolaemic subjects consumed three consecutive treatment diets, each lasting 28 d and separated by 4-week washout periods, using a randomized crossover design. Diets contained 30 % energy as fat, 70 % of which was provided by olive oil (OO), and differed only in the treatment oils: OO, PS esterified to sunflower oil fatty acids (PS-SO), and PS-OO. Both PS-SO and PS-OO treatments provided 1.7 g PS /d. PS-OO and PS-SO consumption resulted in a decrease (P = 0.0483) in LDL-cholesterol (LDL-C) concentrations compared with the OO diet. Although total cholesterol and apo B-100 levels were not significantly affected, PS-SO and, to some extent, PS-OO reduced the total:HDL-cholesterol (HDL-C) ratio (P = 0.0142) and the apo B-100:apo A-I ratio (P = 0.0168) compared with the OO diet. There were no differences across diets in lipoprotein(a) (Lp(a)) and lipid peroxidation levels. However, following consumption of OO and PS-SO, Lp(a) concentrations increased (P = 0.0050 and 0.0421, respectively), while PS-OO treatment did not affect Lp(a) levels. Furthermore, there was a decrease (P = 0.0097) in lipid peroxidation levels with PS-OO treatment during the supplementation phase. Our results suggest that supplementing an OO-rich diet with PS-OO favourably alters the plasma lipid profile and may decrease the susceptibility of LDL-C to lipid peroxidation in hypercholesterolaemic subjects.

The objective of the present study was to compare the effects of dietary diacylglycerol (DAG) oil with triacylglycerol (TAG) oil with a similar fatty acid composition (fatty acid chain range: C14-C22, C18 fatty acid chain: >90%) on protein kinase C (PKC) activation and on 1,2-DAG levels. Using male Wistar rats, no differences in cytosolic and membrane PKC activities in the lingual, esophageal, gastric, small intestinal, cecal, proximal colonic, and distal colonic mucosa were found between the 5% DAG and TAG oil groups, or between the 23% DAG and TAG oil groups after 1 month of feeding. The 1,2-DAG levels in the cecum and colon contents and in the feces and serum in male Wistar rats after a diet containing either 10% DAG or TAG oil feeding were similar between the groups. Moreover, exposure of Caco-2 cells to DAG and TAG oils had no effect on PKC activity in the membrane fraction, but 1,2-dioctanoyl glycerol composed of short-chain fatty acids (C8) did, suggesting the absence of an influence on PKC activity in DAG and TAG oils composed of long-chain fatty acids. In summary, the effects of DAG oil ingestion on PKC activity in the digestive tract and lingual mucosa, and on 1,2-DAG levels in the cecum and colon contents and in the feces and serum were similar to those observed for TAG oil ingestion.

Recent studies of the relation between serum triacylglycerol concentration and the risk for coronary artery disease suggest that inefficient clearance of postprandial triacylglycerols promotes atherogenesis. We recently demonstrated that dietary diacylglycerol (DAG), rich in the 1,3-species, suppresses the postprandial increase in serum triacylglycerol levels compared with dietary triacylglycerol (TAG). Here, we investigated the effects of dietary DAG on atherosclerosis in rabbits with cholesterol-induced atherosclerosis. New Zealand White rabbits (n = 20) were fed a diet containing 3% lard and 1.3% cholesterol for 50 d to induce atherosclerotic lesions. Thereafter, the rabbits were assigned to 2 groups and fed 90 g/d nonpurified diet and orally administered 5 g DAG or TAG for an additional 34 d. Reference rabbits (n = 5) were fed only the nonpurified diet throughout the 84-d study. The area of atherosclerotic lesions and aortic lipid concentrations were significantly lower in DAG-fed rabbits compared with TAG-fed rabbits. The VLDL receptor and macrophage antigen-1 mRNA expression levels were significantly lower in DAG-fed rabbits than in TAG-fed rabbits. In the liver of DAG-fed rabbits, the triacylglycerol concentration was lower and the carnitine palmitoyltransferase activity higher than in TAG-fed rabbits. Stimulation of hepatic lipid catabolism might be related to the reduced lipid accumulation in the liver and aorta by reducing the release of triacylglycerol into the circulation. Thus, long-term consumption of DAG, which reduces postprandial lipemia, might be useful for the regression of atherosclerosis by stimulating hepatic lipid catabolism and thereby modulating monocyte/macrophage migration and aortic lipid accumulation.

Objective: Activation of nonselective cation channels of the transient receptor potential canonical (TRPC) family has been associated with hypertension. Whether store-operated channels, which are activated after depletion of intracellular stores, or second-messenger-operated channels, which are activated by 1-oleoyl-2-acetyl-sn-glycerol, are affected in essential hypertension is presently unknown., Methods: Using a polymerase chain reaction, an in-cell western assay and the fluorescent dye technique we studied TRPC3, TRPC5, and TRPC6 expression and store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx into human monocytes in 19 patients with essential hypertension and in 17 age-matched and sex-matched normotensive control individuals., Results: We observed a significantly increased expression of TRPC3 and TRPC5, but not TRPC6, in essential hypertension. Store-operated calcium influx was significantly elevated in essential hypertension. Store-operated calcium influx was reduced by the inhibitor 2-aminoethoxydiphenylborane, specific TRPC3 and TRPC5 knockdown, but not TRPC6 knockdown using gene silencing by RNA interference. 1-Oleoyl-2-acetyl-sn-glycerol-induced calcium influx and barium influx were also significantly elevated in essential hypertension. The 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx was reduced by TRPC3 and TRPC5 knockdown., Conclusion: We demonstrated an increased TRPC3 and TRPC5 expression and a subsequently increased store-operated calcium influx and increased 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx in monocytes of patients with essential hypertension. This increased activation of monocytes through TRPC channels in patients with essential hypertension may promote vascular disease in these patients.

The antiatherogenic properties of a novel dietary formula (PS-CO) of plant sterol esters of fatty acids, produced by enzymatic interesterification of plant sterols with canola oil (CO), in a CO matrix containing 1,3-diacylglycerol, were evaluated in apolipoprotein E-deficient mice. PS-CO consumption strongly tended to lower total plasma cholesterol levels by 21%, compared to the placebo group. Blood triglycerides were reduced by 38% and 36% compared to CO and placebo-fed mice, respectively. Serum lipid peroxide levels were lowered following PS-CO administration by 62% and 63%, compared to CO and placebo administration, respectively. Unlike CO supplementation, PS-CO consumption preserved serum paraoxonase (PON1) activity. Mouse peritoneal macrophages from PS-CO-fed mice exhibited reduced cellular uptake of oxidized-LDL compared to those from placebo-fed mice and demonstrated a tendency toward a decreased capability to release superoxide anions. These findings indicate that PS-CO supplementation is beneficial in reducing serum lipid levels, and serum and macrophage oxidative stress, thus contributing to the reduction in atherogenic risk factors.

The present study compared the effects of dietary diacylglycerol (DG) and triacylglycerol (TG) oil on lipid metabolism in rats fed a 5% fat (AIN-76) diet for 6 weeks. The plasma and hepatic lipids, hepatic cholesterol-regulating enzyme activity, and hepatic and adipose tissue fatty acid metabolism enzyme activities were determined. Among plasma lipids, triglyceride, free fatty acid, and phospholipid concentrations were significantly lower in the DG group than in the TG group. A lower plasma TG level was accompanied by an increase in adipocyte lipoprotein lipase activity. The hepatic triglyceride level was significantly (P < .001) lowered in the DG group, which was attributable to an increased fatty acid oxidation enzyme (beta-oxidation) activity and a reduced fatty acid synthesis enzyme (glucose-6-phosphate dehydrogenase) activity. The plasma cholesterol concentration was significantly lower in the DG group and was accompanied by a lower hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity. The DG oil used in this study was beneficial for enhancing lipid metabolism with apparent hypolipidemic effects.

Background: The incidence of hyperlipidemia in children is increasing in Japan, but drug therapy for such children is limited. The ingestion of 4% phytosterols-containing diacylglycerol (PS/DAG) decreases serum total cholesterol and low density lipoprotein cholesterol (LDL-C) concentrations in adults. In the present study, we examined the effect of PS/DAG as part of a diet therapy in pediatric patients with hyperlipidemia., Methods: Pediatric patients with hyperlipidemia with > or =5.18mmol (200 mg/dL) serum total cholesterol and/or >or =1.70mmol (150 mg/dL) triglycerides (N=22) ingested bread containing PS/DAG (total daily intake, 10g) for 6 months. Blood chemistry was examined prior to and 2, 4, 6 months after the initiation of ingestion, and 4 months after the ingestion period., Results: No significant differences in energy intake or cholesterol intake during the study period were found. After 4 months of ingestion of PS/DAG, LDL-C, lipoprotein(a) [ Lp(a)], free fatty acids and total ketone bodies decreased significantly. In seven patients with familial hypercholesterolemia, total cholesterol and remnant-like lipoprotein particles (RLP)-cholesterol also significantly decreased in addition to LDL-C and Lp(a)., Conclusions: PS/DAG improves serum lipid metabolism in pediatric patients with hyperlipidemia for whom drug therapy is limited, suggesting that PS/DAG may reduce the risk of developing various diseases induced by hyperlipidemia.

Studies have shown several beneficial effects of dietary diacylglycerol oil (DAG oil), but the mechanism behind these effects is still not clear. One hypothesis is that an increase in portal vein transport of nonesterified fatty acids (NEFA) with subsequent oxidation in the liver might be responsible for the positive effects. We examined the portal vein transport of NEFA and other lipid related variables, in response to DAG and triacylglycerol (TAG) bolus feeding and a bolus of standard pig feed in 4 portal vein and mesenteric artery catheterized pigs. Also, the effect of the boluses on postprandial lipid variables was examined. Portal vein transport of NEFA did not differ when pigs were administered the 2 oil bolus diets, consistent with the similar portal plasma concentrations of oleic and linolenic acids during h 1 after feeding. Glycerol, on the contrary, was transported by the portal vein to a much higher degree after intake of DAG oil (P < 0.001; 20, 40, and 60 min). The postprandial arterial TAG response at 5 and 6 h postprandially was significantly lower after the DAG bolus intake. Analysis of Delta AUC for the 6-h postprandial period of selected and total fatty acids showed a lower concentration of vaccenic acid (P = 0.002) after the DAG bolus diet. In conclusion, DAG bolus feeding did not increase the portal transport of NEFA, but it did increase the portal transport of glycerol and lower the postprandial lipid concentration in arterial plasma.

Obesity in dogs and cats have been increasingly recognized in recent years. Because obesity underlies various diseases, pet owners and veterinarians have an important responsibility to help animals lose weight and maintain their health. Diet therapy, however, is typically based on limited calorie intake and animals may suffer stress from hunger and this is also a concern to animal owners. For this reason, many clients drop out of weight control programmes. In the present study, we focused on dietary diacylglycerol (DAG) as a potentially effective ingredient for canine weight control without caloric restriction. We replaced a portion of the fat in dog food with either DAG or triacylglycerol (TAG), referred to as DAG or TAG diets here, and fed overweight beagle dogs (body condition score of 4 or higher) with either the DAG or TAG diet for a 6-week period. Results indicated that, even though the food composition other than fat type were identical, dogs fed the DAG diet showed a statistically significant reduction in body weight averaging a 2.3% reduction within 6 weeks while the TAG-fed dogs maintained their obese body weights. In addition, the DAG group also showed a reduction in body fat content, serum triglyceride and total cholesterol concentrations. These results suggest the possibility of developing a pet food using DAG to control weight and serum lipid levels without compromising caloric intake.

Objective: Indigestible dextrin (IDex) and diacylglycerol (DG) are food components with physiologic effects on lipid metabolism. Because simultaneous intake of dietary components with similar physiologic functions may produce a beneficial decrease in risk factors for lifestyle-related diseases, we investigated the physiologic effects of simultaneous IDex and DG intake., Methods: Five-week-old male Wistar rats were fed a cholesterol-containing diet with IDex and DG (separately and combined) for 28 d., Results: IDex significantly decreased serum triacylglycerol concentration and increased the length of small intestinal villi, whereas DG produced significant decreases in serum high-density lipoprotein cholesterol concentration and significant increases in liver cholesterol and triacylglycerol concentrations., Conclusions: IDex intake characteristically decreased serum triacylglycerol concentrations, although no additive or synergistic interaction between DG and IDex was observed. These results indicate that simultaneous intake of food components with similar physiologic functions do not necessarily produce additive or synergistic physiologic benefits.

Objective: The objective of the present study was to verify the effect of a dietary oil, consisting mainly of diacylglycerol (DAG) oil, in a typical meal on postprandial changes in serum triacylglycerol (TAG) and remnant-like particle cholesterol (RLP-C) compared with dietary triacylglycerol (TAG) oil., Methods: In a double-blind, randomized, crossover design, 43 healthy Japanese men and women ingested test meals (2093 kJ of energy, 30 g of protein, 19 g of lipids, and 51 g of carbohydrates) containing 10 g of DAG oil (DAG meal) or TAG oil (TAG meal). Blood samples were collected in a fasting state (0 h) and at 2, 3, 4, and 6 h after ingestion of the meal., Results: Postprandial TAG, RLP-C, and chylomicron TAG concentrations were significantly lower after the DAG meal compared with the TAG meal. In 29 subjects with fasting serum TAG levels of at least 1.13 mmol/L (100 mg/dL), differences in postprandial serum changes between meal types were even more remarkable and the incremental areas under the response curve (0 to 6 h) for serum TAG and RLP-C concentrations after the DAG meal were significantly smaller than those after the TAG meal., Conclusions: These results suggest that DAG oil in the daily diet is useful for the prevention of postprandial hyperlipidemia and related disorders.

Introduction: Prevention of arterial thrombotic diseases has high priority in developed countries. An appropriate diet is thought to be the best way to prevent or reduce the risk of mortality from such diseases. The aim of the present study was to evaluate the effect of diacylglycerol (DAG)-rich diets on arterial thrombosis., Material and Methods: Diet-sensitive congenital apolipoprotein E (ApoE) and LDL receptor (LDLR) double deficient mice were used. Thrombosis was assessed by the rate and extent of thrombus formation in the carotid artery of mice after laser irradiation. Plasma total cholesterol and triglyceride levels were measured by enzymatic assays. Four kinds of diets were used: high fat (Western-style) diet contained 20% fat (w/w) and 0.05% cholesterol (w/w); the TAG-rich and the DAG-rich high fat diet contained 20% TAG or DAG oil (w/w) with very similar fatty acid composition and 0.05% cholesterol ; Low fat (Japanese-style) diet contained 7% fat, without cholesterol. These diets were on the basis of AIN93G and were given to mice for 8 weeks from 6 weeks of age., Results: Western-style high fat and TAG-rich high fat diets significantly increased thrombogenicity compared with low fat diet. DAG-rich high fat diet showed the lowest value, and the extent of thrombogenicity was equivalent to the low fat diet group. Fasting plasma total cholesterol level of DAG-rich high fat and low fat diet groups were significantly lower than that of TAG-rich high fat and high fat diet groups. Fasting plasma triglyceride levels in DAG-rich high fat diet group were significantly lower than in the TAG-rich high fat diet group., Conclusions: Dietary DAG but not TAG oil extenuates arterial thrombus formation. The mechanism of this effect is unclear and further investigated.

Objective: Coronary arteriosclerotic heart disease frequently develops in patients with diabetes. Decreases in [corrected] serum high-density lipoprotein cholesterol (HDL-C) [corrected] concentration and low-density lipoprotein (LDL) particle size, accompanied by hypertriglyceridemia, are associated with the onset of atherosclerosis. We recently reported that hypertriglyceridemia was significantly improved in patients with type 2 diabetes who ingested diacylglycerol (DAG) oil. The effect on variables, including LDL particle size related to lipid metabolism, however, was not examined. The present study investigated the effects on these variables in more detail., Methods: Patients with type 2 diabetes (n = 24) were assigned to receive DAG oil or triacylglycerol oil, and a 3-mo, single-blind, controlled study was performed. Patients replaced cooking oil in their daily diet with DAG or triacylglycerol oil, and anthropometry and blood sampling were performed at monthly intervals., Results: There were no significant differences in calorie intake or amount of test oil ingested between groups. Waist circumference and serum triacylglycerol concentrations were significantly lower and serum concentrations of high-density lipoprotein cholesterol and apolipoprotein-AI were significantly higher in the DAG oil group than in the triacylglycerol oil group. Plasma plasminogen activator inhibitor-1 concentrations were significantly lower in the DAG oil group. LDL particle size tended to increase in the DAG oil group and was significantly larger in patients who had a small initial LDL particle size (<25.5 nm). There were no significant differences in variables related to glucose metabolism or in serum concentration of free fatty acids or total ketone bodies., Conclusions: These results indicate that DAG oil may be useful for patients who have type 2 diabetes in the management of obesity and lipid abnormalities.

Introduction: We have shown earlier that diacylglycerol (DAG) but not triacylglycerol (TAG) inhibited thrombus formation. The aim of the present study was to investigate the mechanism of this antithrombotic effect of DAG., Materials and Methods: Four different diets, the (1) Western-style high-fat diet (HFD) containing 20% lipid and 0.05% cholesterol (w/w), (2) TAG-rich and (3) DAG-rich HFDs containing 20% lipid and 0.05% cholesterol, but all lipid replaced by TAG or DAG oil with very similar fatty acid composition and the (4) Japanese-style low-fat diet (LFD) containing 7% oil but no cholesterol were given to apolipoprotein E and low-density lipoprotein (LDL) receptor double-deficient mice. Atherogenicity was assessed by morphology, mapping the whole aorta and measuring the total area of lipid-stained lesions. Endothelial function was measured by the flow-mediated vasodilation test. Platelet reactivity was assessed from native blood sample by a shear-induced platelet function test (hemostatometry). Serum lipoprotein profile was measured by HPLC., Results: Both the Western-style and the TAG-rich HFDs have accelerated atherosclerosis. In contrast, DAG-rich HFD inhibited the atherosclerotic process to an extent comparable with the Japanese-style LFD. There was no significant difference in platelet and coagulant activity between the studied diet groups. DAG-rich but not the TAG-rich HFD significantly suppressed serum LDL cholesterol level., Conclusions: The present findings suggest that the mechanism of antithrombotic and anti-atherogenic effect of DAG may involve the protection of the vascular endothelium from injury and lowered serum LDL cholesterol., (Copyright 2006 S. Karger AG, Basel.)

Objective: The present study compared the effect of corn oil, diacylglycerol (DG) oil, and DG-enriched structured lipids (SL-DG) produced from corn oil, capric and conjugated linoleic acid on adiposity in rats fed an AIN-76 diet (5% fat) for 6 weeks., Methods: The plasma and hepatic lipids, adipose tissue weight, and enzyme activities related to fatty acid metabolism were determined., Results: The weights of the epididymal white adipose tissue (WAT), perirenal WAT, and interscapular WAT were significantly lower in the SL-DG group than in the DG group. Reduction of fat mass in the SL-DG group was related to suppressing fatty acid synthase activities and enhancing beta-oxidation activity in perirenal WAT. The plasma leptin was lower in the SL-DG group than in the DG group, plus a lower plasma TG level was accompanied by an increase in adipocyte LPL activity. Meanwhile the SL-DG supplement lowered the plasma and hepatic cholesterol level. In addition, the hepatic HMG-CoA reductase and ACAT activities were significantly lower in the SL-DG group than in the other groups., Conclusion: The DG-enriched SL used in this study was effective in enhancing triglyceride metabolism in adipose tissue, especially as regards reducing the abdominal fat mass and cholesterol metabolism in the liver., (Copyright 2006 S. Karger AG, Basel.)

Objective: This study examined the effects of a diacylglycerol (DAG)-containing diet on postprandial energy expenditure and respiratory quotient., Methods: A randomized, double-blind, crossover, placebo-controlled study with a washout period was performed in 13 healthy male subjects. A 4240-kJ diet containing 30 g of triacylglycerol (TAG) or DAG (TAG meal or DAG meal, containing 34.5% lipids, 52.1% carbohydrates, and 14.1% proteins) was administered after a fasting period of 15 to 16 h. Breath and serum were analyzed for up to 5 h after ingestion of the meal., Results: The amount of change in energy expenditure 3 h after loading with the DAG meal tended to be higher than that after loading with the TAG meal (P < 0.1). Changes in respiratory quotient 2 and 5 h after loading with the DAG meal were significantly lower than those after loading with the TAG meal, suggesting high lipid oxidation activity after the meal. The serum insulin level 0.5 h after loading with the DAG meal was significantly lower than that after loading with the TAG meal. This result suggests that there is a smaller stimulus in the direction of fat storage after loading with the DAG meal., Conclusions: Compared with the TAG-containing meal, the DAG-containing meal tended to produce a higher postprandial energy expenditure and a significantly lower postprandial respiratory quotient. These results suggest that the DAG-containing meal has high postprandial lipid oxidation activity and a potential effect on high diet-induced thermogenesis.

Objective: The aim of the present study was to determine the effects of dietary diacylglycerol (DG) on the metabolism of lipids and glucose in type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats., Methods: In experiment 1, the rats were orally administered 10 mL/kg of a triacylglycerol (TG) or DG emulsion (15% [w/v] oil), and the subsequent changes in the serum lipid levels were compared. In experiment 2, the rats were fed diets containing 15% DG or TG oil. After 22 weeks, the serum levels of lipids, glucose, and cytokines were determined. In addition, an oral glucose tolerance test (OGTT) was performed on the rats., Results: Administration of an oral fat load caused marked hypertriglyceridemia with a peak at 2 h. Oral DG loading reduced the serum TG increase; the difference between the groups was significant at 4 and 6 h (P < 0.05). Diacylglycerol also markedly reduced the serum free fatty acid concentration increase due to the fat load. After 22 weeks of feeding, dietary DG reduced serum TG levels in the non-fasting state. Moreover, an OGTT revealed enhanced glucose disposal in the DG-fed rats compared with the TG-fed rats. Serum levels of adiponectin, an important insulin-sensitizing adipocytokine, were higher in the DG-fed rats than in the TG-fed rats (P < 0.05). In addition, DG-feeding reduced serum levels of C-reactive protein, a cardiovascular risk factor (P < 0.05)., Conclusion: These results suggested that dietary DG improves lipid metabolism and glucose tolerance, and retards the progress of diabetes mellitus in OLETF rats.

The effects of diacylglycerol ingestion on postprandial lipid metabolism in non-diabetic subjects with and without insulin resistance were investigated. This was single dose ingestion study, in a double blind cross over manner and postprandial lipid concentrations were compared between diacylglycerol oil (DAG) and triacylglycerol oil (TAG) ingestion. The subjects were 18 male volunteers and homeostasis model assessment (HOMA-R) was used to classify them into insulin sensitive (IS, n=10, HOMA-R<2.0) and insulin resistant (IR, n=8, HOMA-R> or =2.0) groups. Fasting serum triglycerides (TG) and remnant-like particle cholesterol (RLP-C) correlated with HOMA-R and were significantly higher in the IR as compared to the IS group. Postprandial increments of TG and RLP-C after DAG ingestion were significantly lower as compared to those after TAG ingestion. In a case of TAG ingestion, their increments positively correlated with HOMA-R and were significantly higher in the IR as compared with the IS group. In contrast, their increments remained constant after DAG ingestion in both groups. In the IR group, the postprandial lipidemia were reduced after DAG ingestion to about half of those after TAG ingestion. In conclusion, DAG reduced postprandial lipidemia especially in subjects with insulin resistance and may be beneficial in preventing atherosclerosis and related diseases.

Insulin resistance-related obesity and diabetes mellitus are the predominant causes of fatty liver disease. Here we examine the effects of dietary diacylglycerol (DG), which is a minor component of plant oils, on lipid accumulation and the expression of genes involved in lipid metabolism in the liver. The animals were fed diets containing either 10% triacylglycerol (TG), 10% TG + 4% alpha-linolenic acid-rich TG (ALATG) or 10% TG + 4% alpha-linolenic acid-rich diacylglycerol (ALADG) for a period of 1 month. Supplementation with ALADG significantly inhibited hepatic triglyceride accumulation; this was accompanied by the up-regulation of beta-oxidation activity, and acyl-CoA oxidase (ACO) and medium-chain acyl-CoA dehydrogenase (MCAD) mRNA levels. By contrast, no significant changes were observed in the levels of peroxisome proliferator-activated receptor-alpha (PPARalpha) and sterol regulatory element-binding protein-1 (SREBP-1) mRNAs. These results indicate that ALADG might be useful in the prevention of fatty liver formation; this effect could be closely related to the stimulation of lipid catabolism in the liver. In addition, our findings suggest that both acylglycerol structure (that is, the structural difference between TG and DG) and fatty-acid species affect the nutritional behaviour of dietary lipids.

The present study investigated the metabolic fate of dietary TAG and DAG and also their digestion products in the stomach and small intestine. A diet containing 10% TAG or DAG oil, enriched in 1,3-DAG, was fed to Wistar rats ad libitum for 9 d. After 18 h of fasting, each diet was re-fed ad libitum for 1 h. The weights of the contents of the stomach and small intestine were measured, and the acylglycerol and FFA levels were analyzed by GC at 0, 1, and 4 h after the 1-h re-feeding. The amounts of re-fed diet ingested and the gastric and small intestinal content were not different between the two diet groups. In the TAG diet group, the main products were TAG and DAG, especially 1(3),2-DAG. In addition, 1,3-DAG and 1(3)-MAG were present in the stomach, and the 1,3-DAG levels increased over time after the re-feeding period. In the DAG diet group, the main products in the stomach were DAG, MAG, FFA, and TAG. There were significantly greater amounts of 1,3-DAG, 1(3)-MAG, and FFA in the DAG diet group in the stomach compared with the TAG diet group. The amount of FFA in the stomach relative to the amount of ingested TAG plus DAG in the DAG diet group was higher than that in the TAG diet group. Acylglycerol and FFA levels were considerably lower in the small intestine than in the stomach. These results indicate that, in the stomach, where acyl migration might occur, the digestion products were already different between TAG and DAG oil ingestion, and that DAG might be more readily digested by lingual lipase compared with TAG. Furthermore, almost all of the dietary lipid was absorbed, irrespective of the structure of the acylglycerol present in the small intestine.

Background: We previously reported that diacylglycerol (DAG) as compared with triacylglycerol (TAG) suppressed increases in postprandial lipids in healthy volunteers. This study was to investigate the effects of DAG on postprandial lipids, particularly remnant lipoproteins in diabetics., Methods: Emulsified DAG oil or TAG oil with a fatty acid composition similar to DAG oil was orally administered (30 g fat/m2 of body surface) to moderately controlled six diabetics, with hemoglobin A1c (HbA1c) below 8%, after fasting for at least 12 h in a randomized crossover manner. Serum cholesterol and TAG, lipids in remnant-like particles (RLP), and other lipid parameters including serum ketone bodies were measured prior to and 2, 4, and 6 h after fat loading., Results: DAG loading significantly suppressed increases in postprandial serum TAG and lipids in RLP as compared with TAG loading. The incremental area under the curve (IAUC) for serum TAG and that for lipids in RLP with DAG loading were also significantly smaller than those with TAG loading. However, changes in serum levels of insulin, free fatty acids, and ketone bodies during fat loading were essentially the same for DAG and TAG., Conclusions: This pilot study suggests that substituting DAG intake for TAG may be beneficial to moderately controlled diabetics due to its effect in reducing postprandial hyperlipidemia.

Dietary diacylglycerol (DAG) oil is an edible oil enriched in DAG (more than 80%). A recent investigation indicated that DAG oil or its components may have beneficial effects on the prevention and management of obesity. We evaluated the genotoxic potential of DAG oil using standard genotoxicity tests. Bacterial reverse mutation assay (Ames test), the chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), and a bone marrow micronucleus assay in ICR CD mice were employed in the present study. In addition we have tested the possibility that genotoxic substances may be formed during cooking, heated DAG oil (HDG) was prepared by batch frying potato slices in the oil at 180 degrees C for 8 h/day for three consecutive days. Therefore, genotoxicity tests were also performed on HDG. Results obtained did not show any genotoxic effect on either unheated DAG oil (UDG) or HDG. We conclude that there are no safety concerns on the genotoxicity of DAG oil under the conditions for normal use.

We investigated postprandial and long-term effects of dietary diacylglycerol (DAG) on serum triacylglycerol (TAG) levels in a 34-year-old man homozygous for complete lipoprotein lipase deletion (LPL deletion). In study 1, Three different oils (DAG, TAG, or medium-chain fatty acid TAG [MCT]) were ingested to examine differences in the postprandial serum TAG response. Postprandial serum TAG levels after DAG oil ingestion were lower than those after TAG oil ingestion and similar to those after MCT oil ingestion. In study 2, the patient was allowed to ingest ordinary cooking oil for 2 months and then DAG oil (containing 80% DAG; target, 20 g/d) for the next 3 months. During the test period, serum TAG levels were measured and dietary evaluations were performed every month. The patient was provided with dietary instruction and consultation at each clinical visit. Serum TAG levels were 1939 to 2525 mg/dL when he used ordinary cooking oil, 1926 to 1173 mg/dL when he used ordinary cooking oil together with DAG oil, and 749 mg/dL when he used DAG oil alone. The TAG intake decreased from 86.9 to 43.0 g and the DAG intake increased from 0.9 to 12.4 g during the study period. Subsequently, 45 g DAG oil (equivalent to 36 g DAG) per day was consumed, and the serum TAG level increased to 2195 mg/dL. Although there was a positive correlation between the TAG intake and serum TAG levels during the period of DAG oil use (P < .01, y = 33.7x - 583.1), there was no such correlation between DAG oil intake and serum TAG levels. These results suggested that substitution of 12.0 g/d DAG (equivalent to 15 g DAG oil) for TAG oil had the same effect as reducing TAG oil consumption for controlling the serum TAG levels in an LPL-depleted patient with hypertriglyceridemia. In conclusion, the results of study 1 and study 2 demonstrate that DAG oil might be replaced by MCT oil as cooking oil for those with LPL deletion.

Aims: The long-term effects of dietary diacylglycerol (DAG) on body fat and lipid metabolism were studied in patients undergoing hemodialysis (HD)., Methods: Ten patients (seven males, three females) ranging in age from 40 to 64 years were enrolled. During the test period, 9.8 g of DAG was ingested per day for 3 months., Results: Body mass index did not change throughout the study. The abdominal fat area measured by CT scan decreased significantly at 3 months, and increased significantly 3 months after completion of the DAG ingestion period. The serum composition of very low-density lipoprotein (VLDL) decreased significantly at 3 months and high-density lipoprotein (HDL) increased significantly at 3 months; these were determined using polyacrylamide gel electrophoresis. Serum lipoprotein (a) decreased significantly at 3 months., Conclusions: Our study showed that 3-month ingestion of DAG reduced the amount of abdominal fat and improved serum lipid profiles in free-living HD patients.

With the approval for use in foods in Japan and the United States, the use of diacylglycerol (DAG) oil in fat-based products may become extensive due to equivalent physicochemical properties to conventional triacylglycerol (TAG) oil. The objective of the present study was to compare the effects of high-dose consumption of DAG oil in humans with that of TAG oil. In a double-blind controlled parallel trial, moderately lean men (n=42) and women (n=39) consumed either DAG or TAG at a dose of approximately 0.5 g/kg body weight/day as part of their diet for 12 weeks. All subjects completing the study tolerated the test oils well and showed no overt effects. Total caloric and fat intake remained constant and showed no significant differences between the groups. There was no significant difference in the occurrence of clinical signs and physical complaints related to test oil consumption. Although some statistically significant effects were reported in hematological and serum chemistry parameters in both DAG and TAG groups, none of these reported changes were considered biologically significant. Overall, this 12-week clinical study revealed no significant or treatment-related adverse effects of DAG oil consumed at a dose of 0.5 g/kg of body weight/day as part of the diet.

The inhibitory effects of 1,3-diacylglycerol (DAG) on diet-induced lipid accumulation in liver and abdominal adipose tissue of rats were investigated in the present study. Male Sprague-Dawley rats were given free access to diets containing 7 wt% TAG (low TAG), 20 wt% TAG (high TAG), or 20 wt% DAG (high DAG), respectively, for 8 wk. The body weight of rats in the 20% high-TAG group increased significantly, and the weights of their abdominal adipose tissue and liver also showed a significant increase compared with rats in the low-TAG group. However, the high-DAG diet resulted in both a significant reduction in body weight gain (with a decrease of 70.5%) and an increase in the ratio of abdominal fat to body weight (by 127%) compared with the high-TAG diet. As well, the liver TAG and serum TAG levels of the high-DAG group were significantly lower than those of the high-TAG group. These effects were associated with up-regulation of acyl-CoA carnitine acyltransferase (ACAT) and down-regulation of acyl-CoA DAG acyltransferase (DGAT) in the liver. However, no significant difference was observed in the activities of alanine aminotransferase and aspartate aminotransferase among the groups (P > 0.05). The present results indicate that dietary DAG reduced fat accumulation in viscera and body, and these effects may be involved with up-regulation of ACAT and down-regulation of DGAT in the liver.

Objective: The present study investigated the effects of phytosterols (PS) in combination with diacylglycerol (DAG) versus PS in combination with triacylglycerol (TAG) on serum lipids and atherosclerosis in cholesterol-fed rabbits., Methods: Cholesterol-fed (0.3%) New Zealand white rabbits were treated with a control diet, a 0.3% PS and 7% TAG diet, or a 0.3% PS and 7% DAG diet for 14 wk., Results: Serum total cholesterol level in the PS/DAG group was statistically lower than that in the control and PS/TAG groups, whereas serum high-density lipoprotein cholesterol and triacylglycerol levels were not statistically different between these two groups. The ratio of the atherosclerotic lesion area and the mean thickness of the intima in the aortas of the PS/DAG group were statistically lower than those of the control group, whereas there was no statistical difference between the PS/TAG and control groups. In particular, the ratio of the lesion area in the abdominal aorta and the mean thickness of the intima in the thoracic and total aortas of the PS/DAG group were statistically lower than those of the PS/TAG group. The ratio of the atherosclerotic lesion area and the mean thickness of the intima in the aortas correlated positively with total cholesterol exposure level., Conclusions: These findings suggested that PS in combination with DAG as opposed to TAG prevents the development of atherosclerosis via a decrease in total cholesterol exposure level and might be useful as a dietary oil for the prevention of atherosclerosis.

Objective: To compare the keratolytic activities of a drug-free hydrophilic microemulsion (ME) and a drug-free lipophilic ME with water, and with regard to the hydrophilic ME also with a 5% salicylic acid gel on the sole of the foot., Methods: Twenty healthy volunteers had their plantar forefoot, midfoot, and rearfoot stratum corneum blackened with silver nitrate and a photographic developer, and a chromameter was used to determine the extent of removal of this black dye by a* value and L value measurement at 24 and 48 h., Results: Both drug-free MEs produced significantly greater increases in a* value and L value than water, and the hydrophilic ME was also more effective than 5% salicylic acid gel., Conclusion: The irritating effect of MEs is rather negligible on the sole of the foot because of the thick plantar stratum corneum. Both MEs therefore appear suitable for the elimination or prevention of plantar desquamative and hyperkeratotic skin changes., (Copyright 2003 S. Karger AG, Basel)

The effects of dietary 1,3-diacylglycerol-rich oil (DG oil) on glucose and lipid metabolism were investigated in comparison with triacylglycerol (TG) oil in female genetically obese Wistar fatty rats. The obese rats and their lean littermates (8 wk old) were fed a synthetic diet containing 10%, (w/w) DG or TG oil for 5 wk. The body weights, abdominal fat weights, and the plasma and liver TG concentrations were not significantly different due to dietary fat type in the obese and lean rats. The plasma glucose concentrations were significantly elevated by dietary DG oil as compared to TG oil in the portal vein and inferior vena cava of obese and lean rats. The plasma free fatty acid concentrations were markedly elevated by dietary DG oil as compared to TG oil in the portal vein and inferior vena cava of both genotype rats, particularly in the obese rats. In the glucose tolerance test, the obese rats fed DG oil showed glucose intolerance, possibly due to the markedly elevated plasma free fatty acids. Thus, the effects of dietary DG oil on lipid-lowering effects and anti-obesity were not observed in either genotype in the present study. Moreover, it is remarkable that glucose intolerance was induced by dietary DG oil in the genetically obese rats. dietary

Unlabelled: In a double-blind parallel-group study, serum lipids and visceral fat/total fat ratio in young women (n=49) with variants of lipid transporters, i.e., fatty acid binding protein 2 (FABP2) and microsomal triglyceride transfer protein (MTP), were analyzed by substituting dietary triacylglycerol (TAG) with sn-1,3-diacylglycerol (DAG). All subjects, including some with the hyperlipidemia-prone genotypes Ala54Thr of FABP2 and c-493g of MTP, received DAG or TAG (20 g/day) for 8 weeks. Reductions of serum lipids from weeks 4 to 8 in FABP2-Ala54Thr heterozygotes and MTP -493g homozygotes were significantly different between the DAG and TAG groups (p<0.05, p<0.01). Visceral fat/total fat (%), as determined by computed tomography (CT), was lower in FABP2-Ala54Thr heterozygotes (p<0.05) of the DAG group. The apoCII/CIII ratio was higher in the DAG group than in the TAG group (p<0.01). Other variants of lipid metabolism, including peroxisome proliferator activated receptors (PPARs) alpha and gamma and SREBP cleavage-activating protein (SCAP), were only slightly affected by dietary DAG., Conclusion: improvement of serum lipid profiles and visceral fat/total fat ratio (CT) was potentiated by DAG intake in subjects with hyperlipidemia-prone genotypes (Ala54Thr heterozygotes of FABP2 and -493g homozygotes of MTP).

The effects of dietary 1,3-diacylglycerol-rich oil (DG oil) on biochemical findings related to glucose and lipid metabolisms were investigated in comparison with triacylglycerol oil (TG oil) in normal rats. Young (7 wk-old) and old (8 mo-old) rats were fed a synthetic diet containing 10% (by weight) DC or TG oil for 1, 4, 8, or 12 wk. The body weights, epididymal and perirenal adipose tissue weights, and feed efficiency were not significantly different in the dietary oil groups during any feeding period. The plasma and liver triacylglycerol concentrations were not different in the dietary groups, except that the plasma triacylglycerol concentrations were rather lower only in the portal vein of rats fed DG oil. The plasma glucose and free fatty acid concentrations were significantly higher in rats fed DG oil as compared to TG oil. In the old rats fed DG oil for 8 wk, the fasted plasma glucose and insulin concentrations were elevated and glucose intolerance was observed. The insulin receptor expression was not different due to dietary oil, but was markedly reduced with aging. Thus, the anti-obesity and lipid-lowering effects of dietary DG oil were not found. Moreover, it appeared that the glucose intolerance might be induced by dietary DG oil, particularly in the old rats.

Purpose of Review: Diacylglycerol is an intermediate product of triacylglycerol hydrolysis and comprises up to 10% of glycerides in plant-derived edible fats and oils. Recent developments in oil chemistry have led to the availability of a novel diacylglycerol oil for clinical studies. Recent research has shown that the oil containing 70% of unusual 1,3- species has metabolic characteristics distinct from those of triacylglycerol of similar fatty acid composition. This review summarizes recent research in humans and experimental animals into the metabolic effects and possible mechanisms of action of this oil., Recent Findings: Consumption of the oil affects lipid metabolism including lowering of plasma triacylglcerol, decreases postprandial lipemia and reduces body fat mass, compared with triacylglcerol. As the fatty acids of the two oils are similar, the metabolic differences reside in their structural differences., Summary: It is still uncertain whether longer term consumption of the diacylglycerol oil will lead to persistent and consistent reductions in plasma triacylglycerol and body fat. However future studies may demonstrate a role in managing aspects of the metabolic syndrome.

Several recent studies have demonstrated that dietary DAG oil rich in 1,3-species suppresses the postprandial increase of serum TAG level and decreases body fat accumulation, compared with TAG oil. To clarify the mechanisms underlying the beneficial effects of DAG, we investigated the metabolic features of DAG in the small intestine with regard to the digestion pathway in the lumen and the TAG-synthesis pathway in the mucosa. When intraduodenally infused as an emulsion, TAG was digested to 1,2-DAG, 2-MAG, and FFA, whereas 1,3-DAG was digested to 1(3)-MAG and FFA. When assessed by the incorporation of [1-14C]linoleic acid in lipids, the mucosal TAG-synthesis was significantly reduced by DAG infusion compared with TAG infusion. However, the mucosal 1,3-DAG synthesis was remarkably increased in the DAG-infused rats. The total amount of mucosal 1,3-DAG was also increased (4.5-fold) after DAG infusion compared with that after TAG infusion. Next, we examined the synthesis pathway of 1,3-DAG. In cultures of the everted intestinal sacs, 1,3-DAG production required the presence of 1-MAG, suggesting that the 1,3-DAG synthesis was due to acylation of 1(3)-MAG in the DAG-infused rats. Furthermore, measurements of DAG acyltransferase activity indicated that 1,3-DAG was little utilized in TAG synthesis. These findings suggest that features of 1,3-DAG digestion and assimilation in the intestine may be responsible for the reduction of the postprandial serum TAG level by dietary DAG.

Background: Diacylglycerol is a natural component of edible oils that has metabolic characteristics that are distinct from those of triacylglycerol., Objective: We assessed the efficacy of an oil containing mainly 1,3-diacylglycerol in reducing body weight and fat mass when incorporated into a reduced-energy diet., Design: The study was a randomized, double-blind, parallel intervention trial that was conducted at an outpatient clinical research center. The subjects (n = 131) were overweight or obese men (waist circumference > or = 90 cm) and women (waist circumference > or = 87 cm). Food products (muffins, crackers, soup, cookies, and granola bars) containing diacylglycerol or triacylglycerol oil and having the same fatty acid composition were incorporated into a reduced-energy diet (2100-3350-kJ/d deficit) for 24 wk. Percentages of change in body weight, fat mass, and intraabdominal fat area were assessed., Results: In an intention-to-treat analysis, body weight and fat mass decreased significantly more in the diacylglycerol group than in the triacylglycerol group (P = 0.025 and 0.037, respectively). By the end of the trial, mean body weight had decreased 3.6% and 2.5% in the diacylglycerol and triacylglycerol groups, respectively. Fat mass decreased 8.3% and 5.6% in the diacylglycerol and triacylglycerol groups, respectively., Conclusion: Foods containing diacylglycerol oil promoted weight loss and body fat reduction and may be useful as an adjunct to diet therapy in the management of obesity.

Dietary fat contributes to the development of obesity. We examined the effect of dietary diacylglycerol (DG), which is a minor component of edible oils, on the development of obesity and expression of genes involved in energy homeostasis in C57BL/KsJ-db/db mice. Mice were fed diets containing either 14 g/100 g (%) triacylglycerol (TG), 10% TG + 4% alpha-linolenic acid-rich TG (ALATG), or 10% TG + 4% alpha-linolenic acid-rich diacylglycerol (ALADG) for 1 mo. Mice fed ALADG, but not ALATG had less body weight gain and higher rectal temperature than the TG-fed controls. These effects were accompanied by up-regulation of acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, fatty acid binding protein, and uncoupling protein (UCP)-2 mRNA and beta-oxidation activity in the small intestine. In contrast, the treatments did not affect beta-oxidation and related gene expressions in the liver or UCP-3 mRNA level in skeletal muscle. These results indicate that stimulation of lipid metabolism in the small intestine might be closely related to the antiobesity and thermogenic effects of dietary DG. In addition, structural differences between DG and TG, not variations in the composition of fatty acids, are responsible for the different effects of the lipids.

LPDII vectors are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA (polyplexes) complexed with anionic pH-sensitive liposomes. Here, we describe a novel LPDII formulation containing polyethylenimine (PEI) polyplexes complexed with anionic pH-sensitive liposomes composed of diolein/cholesteryl hemisuccinate (CHEMS) (6:4 mol/mol). The pH-sensitivity of diolein/CHEMS liposomes was evaluated through quantitative fluorescence measurements of calcein release and particle size analysis. The results indicated that diolein/CHEMS liposomes are stable at physiological pH, but undergo rapid aggregation and fluorescence dequenching at pH values < or =5.0. Using a luciferase reporter gene, in vitro transfection of KB oral cancer cells showed that the transfection efficiency of LPDII vectors was superior to other well-characterized polyplexes and lipoplexes. Results further showed that gene delivery using diolein-containing LPDII vectors was dependent on the PEI nitrogen/DNA phosphate (N/P) ratio, the lipid/DNA weight ratio and the cell line being transfected. Replacing PEI with poly-L-lysine as the DNA condensing agent resulted in only a moderate reduction in transfection activity. Moreover, in contrast to LPDII formulations incorporating dioleoylphosphatidylethanolamine (DOPE), the transfection efficiency of diolein-based LPDII vectors was sustained in media containing up to 50% fetal bovine serum. Since diolein-based LPDII vectors mediate efficient gene transfer and retain their transfection activity in the presence of serum, diolein may be a promising alternative to DOPE for the construction of non-viral vectors for in vivo gene delivery., (Copyright 2002 Elsevier Science B.V.)

We examined the long-term effects of dietary diacylglycerol (DG) and triacylglycerol (TG) with similar fatty acid compositions on the development of obesity in C57BL/6J mice. We also analyzed the expression of genes involved in lipid metabolism at an early stage of obesity development in these mice. Compared with mice fed the high-TG diet, mice fed the high-DG diet accumulated significantly less body fat during the 8-month study period. Within the first 10 days, dietary DG stimulated beta-oxidation and lipid metabolism-related gene expression, including acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, and uncoupling protein-2 in the small intestine but not in the liver, skeletal muscle, or brown adipose tissue, suggesting the predominant contribution of intestinal lipid metabolism to the effects of DG. Furthermore, analysis of digestion products of [(14)C]DG and those of [(14)C]TG revealed that the radioactivity levels detected in fatty acid, 1-monoacylglycerol, and 1,3-DG in intestinal mucosa were significantly higher after intrajejunal injection of DG rather than TG. Thus, dietary DG reduces body weight gain that accompanies the stimulation of intestinal lipid metabolism, and these effects may be related to the characteristic metabolism of DG in the small intestine.

This study evaluated the potential of poly(iso-butyl cyanoacrylate) (PBCA) nanocapsules dispersed in a biocompatible microemulsion to facilitate the absorption of insulin following intragastric administration to diabetic rats. Insulin-loaded PBCA nanocapsules were prepared in-situ in a biocompatible water-in-oil microemulsion by interfacial polymerisation. The microemulsion consisted of a mixture of medium-chain mono-, di- and tri-glycerides as the oil component, polysorbate 80 and sorbitan mono-oleate as surfactants and an aqueous solution of insulin. Resulting nanocapsules were approximately 200 nm in diameter and demonstrated a high efficiency of insulin entrapment (> 80%). In-vitro release studies showed that PBCA nanocapsules could suppress insulin release in acidic media and that release at near neutral conditions could be manipulated by varying the amount of monomer used for polymerisation. Subcutaneous administration of insulin-loaded nanocapsules to diabetic rats demonstrated that the bioactivity of insulin was largely retained following this method of preparing peptide-loaded nanocapsules and that the pharmacodynamic response was dependent on the amount of monomer used for polymerisation. The intragastric administration of insulin-loaded nanocapsules dispersed in the biocompatible microemulsion resulted in a significantly greater reduction in blood glucose levels of diabetic rats than an aqueous insulin solution or insulin formulated in the same microemulsion. This study demonstrates that the formulation of peptides within PBCA nanocapsules that are administered dispersed in a microemulsion can facilitate the oral absorption of encapsulated peptide. Such a system can be prepared in-situ by the interfacial polymerisation of a water-in-oil biocompatible microemulsion.

We examined the effect of daily consumption of dietary diacylglycerol (DG) oil on serum lipid concentrations in patients with diabetes whose serum triacylglycerol (TG) levels were persistently increased despite continuous nutritional counseling at the outpatient clinic. Patients (n = 16) were divided into DG and control groups (n = 8 each). DG was incorporated (target dose 10 g/d) by substituting DG oil (80 g DG/100 g oil) for the ordinary TG cooking oil used at home for 12 wk. The control group continued consuming ordinary TG cooking oil. Dietary records indicated that there were no differences between groups in total energy intake or percentage of energy from fat. In the DG group, TG intake decreased from 26.8 +/- 9.3 to 15.7 +/- 8.9 g/d, whereas DG intake increased from 0.3 +/- 0.1 to 10.6 +/- 3.9 g/d. No differences between groups were observed in body weight, total fat intake or total oil consumption throughout the study period. In the DG group, serum TG levels decreased 39.4% from 2.51 +/- 0.75 mmol/L to 1.52 +/- 0.28 mmol/L. Serum glycohemoglobin A(1c) (HbA(1c)) concentration also decreased 9.7%. In contrast, there were no changes in these variables in the control group. Serum total and HDL cholesterol were not affected in either group. These results indicate that DG oil may be useful as an adjunct to the standard diet therapy of fat restriction in the management of diabetics with hypertriglyceridemia.

This study deals with the development of gene therapy in the treatment of lung diseases. It reports on the use of ultrasonic nebulization to administer plasmid-lipid complexes to the lungs of mice to transfect their epithelial cells. A plasmid complexed to cationic lipids was aerosolized using an ultrasonic nebulizer. We then characterized the lipoplex size and visualized the lipoplex by electron microscopy. Finally, we assessed the in vivo transgene expression in the lungs further to the aerosolization of different lipid-plasmid formulations. The nebulizer-generated particles were small and looked like a string composed of little and more or less cubic units. Transgene expression was detected in the lungs of mice further to a 20-min exposure to aerosol particles produced with the ultrasonic nebulizer. The results obtained with our optimized plasmid-lipid-NaCl formulation suggest that this route can be used to administer an appropriate gene to the airways for the treatment of respiratory disorders.

Objective: This study was performed to investigate the difference in the serum-cholesterol- and triglyceride-lowering activities between phytosterols dissolved in diacylglycerol (PS/DG) and dispersed in triacylglycerol (PS/TG). The effects of the solvent on the concentrations of serum beta-sitosterol and campesterol were examined., Design: The study had a randomised crossover design., Subjects: Twelve healthy normocholesterolemic or moderately hypercholesterolemic men aged 29-50 y participated in this study., Interventions: For 2 weeks before the test period (designated as the control period), all subjects consumed control mayonnaise (PS free) daily with supper and were randomly assigned to two groups for the 2 week test period; one group was given mayonnaise containing PS (500 mg/day) dissolved in DG (10 g/day), and the other mayonnaise containing PS (500 mg/day) dispersed in TG (10 g/day). After a wash out period consuming control PS-free mayonnaise for 4 weeks, the groups were reversed for 2 weeks., Results: PS/TG feeding had no effect on the serum cholesterol level. In contrast, PS/DG feeding significantly reduced the total and LDL cholesterol levels from the initial value of 5.57 to 5.31 mmol/l (4.7%; P<0.05) and from 3.69 to 3.39 mmol/l (7.6%; P<0.05), respectively. Moreover, the degree of total cholesterol reduction induced by PS/DG feeding in the test period was significantly greater than that induced by PS/TG feeding (P<0.05). In addition, the serum beta-sitosterol and campesterol concentrations did not change during the PS/TG or PS/DG feeding periods., Conclusions: Dissolution of PS in DG had a better serum cholesterol lowering effect than dissolution in TG., Sponsorship: Kao Corporation.