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AimsConjugated linoleic acid (CLA) is a natural constituent of dairy products, specific isomers of which have recently been found to have insulin sensitizing and possible antiobesity actions. Chromium is a micronutrient which, as the picolinate (CrP), has been shown to increase insulin sensitivity in animal models, including the JCR:LA-cp rat. We tested the hypothesis that these agents may have beneficial synergistic effects on the micro- and macrovasculopathy associated with hyperinsulinaemia and early type 2 diabetes.MethodsInsulin-resistant cp/cp rats of the JCR:LA-cp strain were treated with mixed isomers of CLA (1.5% w/w in the chow) and/or CrP at 80 microg/kg/day (expressed as Cr) from 4 weeks of age to 12 weeks of age. Plasma insulin, lipid and adiponectin levels, aortic vascular function, renal function and glomerular sclerosis were assessed.ResultsCLA administration reduced food intake, body weight and fasting insulin in JCR:LA-cp rats. Plasma adiponectin levels were significantly elevated in rats treated with both CLA and CrP. Aortic hypercontractility was reduced and the relaxant response to the nitric oxide-releasing agent acetylcholine (Ach) was increased in CrP-treated rats. Striking reductions were also observed in the level of urinary albumin and the severity of glomerular sclerosis in rats treated specifically with CLA.ConclusionsCLA and CrP have beneficial effects ameliorating several of the pathophysiologic features of an insulin-resistant rat model. These supplements may be useful adjuncts in the management of patients with the metabolic syndrome and warrant further study.

Objective: It is recognized that there is a remarkable variability in the systemic response to high-fat (HF) diets that cannot be completely explained by genetic factors. In addition, pregnancy complications leading to intrauterine growth restriction (IUGR) have been associated with an increased risk of developing metabolic syndrome (MetS) later in life. Thus, we hypothesized that offspring born with IUGR exhibit permanent metabolic changes that make them more susceptible to HF diet-induced MetS.Research Design and Methods: SD rats born normal (control) or with hypoxia-induced IUGR were randomized to low-fat (10% fat) or HF (45% fat) diets. After 9 weeks of feeding, physiological and molecular pathways involved in the MetS were evaluated.Results: IUGR offspring exhibited decreased energy intake and physical activity relative to controls. In offspring fed a HF diet, IUGR was associated with decreased total body fat content, a relative increase in intra-abdominal fat deposition and adipocyte size, an increase in fasting plasma concentrations of leptin, triglyceride and free fatty acids, and an increased concentration of triglycerides and ceramides in both liver and skeletal muscle. These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C , inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin.Conclusions: IUGR enhances specific deleterious metabolic responses to a HF diet. Our results suggest that offspring born with IUGR may require special attention and follow-up to prevent the early onset of MetS. [ABSTRACT FROM AUTHOR]

Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic acid in humans and animals. We have previously shown that 3-wk VA supplementation has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity, and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver and intestine in obese JCR:LA-cp rats. Plasma TG (P < 0.001), total cholesterol (P < 0.001), LDL cholesterol (P < 0.01), and nonesterified fatty acid concentrations, as well as the serum haptoglobin concentration, were all lower in obese rats fed the VA diet compared with obese controls (P < 0.05). In addition, there was a decrease in the postprandial plasma apolipoprotein (apo)B48 area under the curve (P < 0.05) for VA-treated obese rats compared with obese controls. The hepatic TG concentration and the relative abundance of fatty acid synthase and acetyl-CoA carboxylase proteins were all lower (P < 0.05) in the VA-treated group compared with obese controls. Following acute gastrointestinal infusion of a VA-triolein emulsion in obese rats that had been fed the control diet for 3 wk, the TG concentration was reduced by 40% (P < 0.05) and the number of chylomicron (CM) particles (apoB48) in nascent mesenteric lymph was reduced by 30% (P < 0.01) relative to rats infused with a triolein emulsion alone. In conclusion, chronic VA supplementation significantly improved dyslipidemia in both the food-deprived and postprandial state in JCR:LA-cp rats. The appreciable hypolipidemic benefits of VA may be attributed to a reduction in both intestinal CM and hepatic de novo lipogenesis pathways. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is triggered by the retention of apolipoprotein B-containing lipoproteins by proteoglycans. In addition to low-density lipoprotein, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported antiatherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans on arterial proteoglycans., Methods and Results: Solid-phase assays demonstrated that chP3R99 effectively blocked >50% lipoprotein binding to chondroitin sulfate and vascular extracellular matrix in vitro. The preperfusion of chP3R99 (competitive effect) resulted in specific antibody-arterial accumulation and reduced fluorescent lipoprotein retention by ~60% in insulin resistant JCR:LA- cp rats. This competitive reduction was dose dependent (25-250 μg/mL), effectively decreasing deposition of cholesterol associated with lipoproteins. In a 5-week vaccination study in insulin resistant rats with (200 μg subcutaneously, once a week), chP3R99 reduced arterial lipoprotein retention, and was associated with the production of antichondroitin sulfate antibodies (Ab3) able to accumulate in the arteries (dot-blot). Neither the intravenous inoculation of chP3R99 (4.5 mg/kg), nor the immunization with this antibody displayed adverse effects on lipid or glucose metabolism, insulin resistance, liver function, blood cell indices, or inflammation pathways in JCR:LA -cp rats., Conclusions: Both acute (passive) and long-term administration (idiotypic cascade) of chP3R99 antibody reduced low-density lipoprotein and remnant lipoprotein interaction with proteoglycans in an insulin-resistant setting. These findings support the innovative approach of targeting proatherogenic lipoprotein retention by chP3R99 as a passive therapy or as an idiotypic vaccine for atherosclerosis.

Purpose of Review: Remnant cholesterol (RC) is the cholesterol carried in lipoproteins derived from the catabolism of chylomicrons and very low-density lipoproteins. Evidence supporting the causal relationship of RC with atherosclerotic cardiovascular disease (ASVD) is accumulating rapidly. The number of impactful contributions to this field are increasing and provide a pathophysiological insight into the current residual cardiovascular risk beyond low-density cholesterol (LDL)-cholesterol (LDL-C). They also raise the question of whether RC should be used in prediction models and become the target of new therapeutic interventions. The intent of this review is to highlight the recent advances on the role of RC in atherogenesis and the validation of RC as a predictor of ASVD., Recent Findings: Numerous prospective and retrospective cohorts helped validate a significant causal relationship of RC with various forms of ASVD, independent of LDL-C. A recent large Mendelian randomization study reinforced the existence of this relationship and showed that the risk of atherosclerotic events was driven nearly entirely by a direct effect of RC., Summary: Both available and accumulating evidence suggest that a lifelong reduction in RC could translate into a substantial reduction in ASVD risk. The data support a revision of current guidelines to incorporate RC as an independent risk factor for ASVD. We propose that early screening of RC should be implemented and that RC lowering should become the target of future drug developments., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow.

This study investigated how birth weight differences in piglets affected carcass and muscle fiber properties as well as meat quality at slaughter. Within litters, piglets were grouped according to their birth weight as either normal (NBW; 1.62-1.73 kg) or low (LBW; 1.18-1.29 kg). At 5 weeks of age, NBW piglets were randomly transitioned to control (C) or isocaloric high fat diets derived from non-dairy (HF), while LBW piglets were randomly transitioned to high fat diets derived from non-dairy (HF) or dairy sources (HFHD). Piglets were reared in individual pens under standardized housing and feeding conditions. Live weight was recorded weekly, and pigs were slaughtered at 12 weeks of age. Hot carcass weights, dressing percentages, lean meat yield, and primal cut proportions were determined. The m. longissimus thoracis was collected from the right side of the carcass for measurement of physical and chemical properties of meat and muscle fiber characteristics. Results indicated that LBW pigs compensated for their live weight compared to NBW pigs at 6 weeks of age. The mean muscle fiber diameter of LBW-HFHD group is significantly higher than NBW-C and NBW-HF group, and the type I muscle fiber diameter is significantly higher than NBW-C group. Dairy fat inclusion in LBW pig diet reduced carcass back fat thickness. This increased the calculated lean meat yield to be comparable to that of NBW pigs fed a commercial diet. Incorporating dairy-sourced high-fat into LBW pigs' diets appears to be an effective strategy for producing carcasses equivalent to NBW pigs., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Aims: Non-fasting remnant cholesterol (RC) is a novel marker of cardiovascular disease (CVD) risk, however, data on this relationship in Canadians with diabetes (at high risk of CVD) is lacking. The objective of this analysis was to determine the relationship of RC with CVD in individuals with and without diabetes in the Alberta's Tomorrow Project (ATP) cohort., Methods: Non-fasting lipid data collected as part of the ATP was linked to administrative health records (October 2000-March 2015) to ascertain incident CVD and prevalent diabetes. Participants without prevalent CVD or incident diabetes and who had complete, non-negative non-fasting lipid data collected with triglycerides <4.5 mmol/L were included (n = 13,631). The relationship between non-fasting RC and incident CVD diagnoses was assessed by Cox proportional hazards regression, after stratification by diabetes status., Results: Participants were 69.8% women with a mean age of 61.6 ± 9.7 years, and 6.5% had prevalent diabetes. Non-fasting RC was higher in participants with diabetes compared to those without (mean 0.94 ± 0.41 mmol/L vs. 0.77 ± 0.38 mmol/L, p < 0.0001) and was associated with increased risk of incident CVD among those without diabetes (adjusted hazard ratio (aHR) 1.22, 95% CI 1.03-1.43, p = 0.02). Although a similar trend was observed in participants with diabetes it did not reach statistical significance (aHR 1.31, 95% CI 0.84-2.05, p = 0.23)., Conclusions: Elevated non-fasting RC predicted increased CVD risk in middle and older-aged adults without diabetes; similar trends were observed in participants with diabetes and require further testing in a larger sample., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: European studies have shown that nonfasting remnant cholesterol can be a strong predictor of cardiovascular disease risk and may contribute to identifying residual risk; however, Canadian data are lacking on nonfasting remnant cholesterol. In this study, we aimed to determine the relation between nonfasting remnant cholesterol, low-density lipoprotein (LDL) cholesterol and cardiovascular disease among people in Alberta., Methods: In this retrospective analysis, we used data from Alberta's Tomorrow Project, a large prospective cohort that enrolled Albertans aged 35-69 years (2000-2015). Participants with consent to data linkage, with complete nonfasting lipid data and without existing cardiovascular disease were included. The nonfasting remnant cholesterol and LDL cholesterol relation with a composite cardiovascular disease outcome of major incident cardiovascular diagnoses, ascertained by linking to Alberta Health databases, was determined by multivariable logistic regression, adjusting for age, sex, statin use, comorbidities, and LDL cholesterol or remnant cholesterol., Results: The final sample of 13 988 participants was 69.4% female, and the mean age was 61.8 (standard deviation [SD] 9.7) years. Follow-up time was approximately 15 years. Mean remnant cholesterol was significantly higher among individuals with versus without cardiovascular disease (0.87 [SD 0.40] mmol/L v. 0.78 [SD 0.38] mmol/L, standardized mean difference [SMD] -0.24), and mean LDL cholesterol was significantly lower (2.69 [SD 0.93] mmol/L v. 2.88 [SD 0.84] mmol/L, SMD 0.21). The odds of incident composite cardiovascular disease were significantly increased per mmol/L increase in remnant cholesterol (adjusted odds ratio [OR] 1.48, 95% confidence interval [CI] 1.27-1.73) but significantly decreased per mmol/L increase in LDL cholesterol (adjusted OR 0.73, 95% CI 0.68-0.79)., Interpretation: In this large Albertan cohort of predominantly older females, nonfasting remnant cholesterol had a positive relation with cardiovascular disease incidence, whereas LDL cholesterol did not. These findings support the clinical utility of measuring non-fasting remnant cholesterol to detect cardiovascular disease risk., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Purpose: To understand the effects of consuming high-fat and low-fat dairy products on postprandial cardiometabolic risk factors and intestinal immune function, we used an established low birthweight (LBW) swine model of diet-induced insulin resistance., Methods: LBW piglets were randomized to consume one of the 3 experimental high fat diets and were fed for a total of 7 weeks: (1) Control high fat (LBW-CHF), (2) CHF diet supplemented with 3 servings of high-fat dairy (LBW-HFDairy) and (3) CHF diet supplemented with 3 servings of low-fat dairy (LBW-LFDairy). As comparison groups, normal birthweight (NBW) piglets were fed a CHF (NBW-CHF) or standard pig grower diet (NBW-Chow). At 11 weeks of age, all piglets underwent an established modified oral glucose and fat tolerance test. At 12 weeks of age, piglets were euthanized and ex vivo cytokine production by cells isolated from mesenteric lymph node (MLN) stimulated with mitogens was assessed., Results: Dairy consumption did not modulate postprandial plasma lipid, inflammatory markers and glucose concentrations. A lower production of IL-2 and TNF-α after pokeweed mitogen (PWM) stimulation was observed in LBW-CHF vs NBW-Chow (P < 0.05), suggesting impaired MLN T cell function. While feeding high-fat dairy had minimal effects, feeding low-fat dairy significantly improved the production of IL-2 and TNF-α after PWM stimulation (P < 0.05)., Conclusions: Irrespective of fat content, dairy had a neutral effect on postprandial cardiometabolic risk factors. Low-fat dairy products improved intestinal T cell function to a greater extent than high-fat dairy in this swine model of obesity and insulin resistance., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Metabolic syndrome is a worldwide health issue. Previous research has revealed that low-birth weight (LBW) swine fed a high-fat (HF) diet were susceptible to insulin resistance (IR) and developed a preferential intestinal lipid absorption, hypertriglyceridemia, and muscle steatosis. We hypothesized that fatty acid transporters such as CD36, FATP4, and FABP2 could potentially explain the development of these conditions. In addition, dairy-derived fatty acids have been shown to be valid biomarkers to assess dairy intake, which can be utilized to investigate muscle lipid deposition in LBW swine. The overall aim of this study was to delineate molecular transport candidates responsible for intestinal lipid absorption and muscle lipid deposition in LBW swine; and secondly to determine what dietary fatty acids might accumulate preferentially in pork muscle when consuming dairy products. At 5 weeks of age, normal birth weight (NBW) and LBW piglets were randomly assigned to three experimental diets: 1-chow diet, 2-HF diet, or 3-isocaloric HF diet supplemented with full fat dairy products. At 12 weeks of age, piglets were euthanized, and carcass, fasting plasma, biceps femoris and jejunum mucosal scrapings were collected. Results showed that HF-fed LBW swine exhibited early signs of IR (fasting glucose, P < 0.05; fasting insulin, P = 0.091; HOMA-IR, P = 0.086) compared with NBW-Chow, which were attenuated with increased dairy intake. Muscle samples from HF-fed LBW swine contained significantly more triglyceride compared to Chow-fed NBW swine (P < 0.05). Increased dairy intake significantly increased myristic acid (C14:0) and DPA (C22:5n3) relative to HF feeding alone (P < 0.05). All HF-fed LBW swine (regardless of dairy intake) exhibited an upregulation of CD36 expression (but not FABP2) compared with NBW littermates in both the small intestine and muscle (P < 0.05). Interestingly, increased dairy intake significantly increased the Canadian Lean Yield percentage in LBW swine fed an HF diet (P < 0.05). Findings from this study provide evidence on the mechanistic pathway of intestinal and muscle lipid metabolism in an innovative LBW swine model. We have also revealed that increasing dairy intake can enhance the incorporation of dietary long-chain polyunsaturated fatty acids into pork, as well as increasing the predicted lean yield of the carcass., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although dairy intake has been shown to have a neutral or some beneficial effect on major cardiometabolic risk factors, the impact of dairy, and especially dairy fat, on immune function remains to be investigated. To understand the effect of consuming dairy fat on cardiometabolic risk factors and immune function, we used an established low birthweight (LBW) swine model of diet-induced insulin resistance to compare high-fat and low-fat dairy products to a control high-fat diet (CHF). LBW piglets were randomized to consume one of the 3 experimental HF diets: (1) CHF, (2) CHF diet supplemented with 3 servings/day of high-fat dairy (HFDairy) and (3) CHF diet supplemented with 3 servings/day of low-fat dairy (LFDairy). As comparison groups, normal birthweight (NBW) piglets were fed a CHF (NBW-CHF) or standard pig grower diet (NBW-Chow). A total of 35 pigs completed the study and were fed for a total of 7 weeks, including 1 week of CHF transition diet. At 12 weeks of age, piglets were euthanized. Fasting blood and tissue samples were collected. Ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed (PWM), phytohemagglutinin (PHA) and phorbol myristate acetate-ionomycin (PMA-I) were assessed. As expected, LBW-CHF piglets showed early signs of insulin resistance (HOMA-IR, P model = 0.08). Feeding high-fat dairy products improved fasting plasma glucose concentrations more than low-fat dairy compared to LBW-CHF ( P < 0.05). Irrespective of fat content, dairy consumption had neutral effect on fasting lipid profile. We have also observed lower production of IL-2 after PWM and PHA stimulation as well as lower production of TNF-α and IFN-γ after PWM stimulation in LBW-CHF than in NBW-Chow (all, P < 0.05), suggesting impaired T cell and antigen presenting cell function. While feeding high-fat dairy had minimal effect on immune function, feeding low-fat dairy significantly improved the production of IL-2, TNF-α and IFN-γ after PWM stimulation, IL-2 and IFN-γ after PHA stimulation as well as TNF-α after PMA-I stimulation compared to LBW-CHF (all, P < 0.05). These data provide novel insights into the role of dairy consumption in counteracting some obesity-related cardiometabolic and immune perturbations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 She, Wang, Makarowski, Mangat, Tsai, Willing, Proctor and Richard.)

Background: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25-35 kg/m 2 ) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers., Results: AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC., Conclusion: This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization., Trial Registration: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract., (© 2022. The Author(s).)

Obesity has emerged as a leading global health concern. It is characterized by chronic low-grade inflammation, which impairs insulin signaling, lipid metabolism and immune function. Recent findings from animal and clinical studies have begun to elucidate the underlying mechanisms of immune dysfunction seen in the context of obesity. Here, we provide a brief review on the current understanding of the interplay between obesity, dyslipidemia and immunity. We also emphasize the advantages and shortcomings of numerous applicable research models including rodents and large animal swine that aim at unraveling the molecular basis of disease and clinical manifestations. Although there is no perfect model to answer all questions at once, they are often used to complement each other. Finally, we highlight some emerging nutritional strategies to improve immune function in the context of obesity with a particular focus on choline and foods that contains high amounts of choline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 She, Mangat, Tsai, Proctor and Richard.)

High-fat diets (HFD) have been shown to induce substantial shifts in intestinal microbial community composition and activity which are associated with adverse metabolic outcomes. Furthermore, changes in microbial composition are affected by fatty acid composition; saturated, monounsaturated (MUFA), and industrial trans fats (iTFA) adversely affect microbial diversity while polyunsaturated fats (PUFA) have been shown to have neutral effects. The effects of naturally occurring trans fats on gut microbial composition are unknown. Vaccenic acid (VA) is the most abundant naturally occurring trans fat (abundant in meat and dairy), can be elevated by altering a cow's diet, and has been shown to have hypolipidemic effects. The aim of this study was to determine how variations of VA content in beef fat affect gut microbial composition, insulin resistance, and lipid metabolism in pigs. Low birth weight (LBW) and control pigs were fed a control or high-fat, high-carbohydrate (HFHC) diet supplemented with beef fat containing either high or low VA levels for 7 weeks. An adapted modified oral glucose tolerance test and fat challenge test were performed at 9 weeks of age following implantation of jugular catheters. Impacts on microbial composition were assessed using 16S rRNA gene amplicon sequencing. The HFHC diet containing beef fat rich in VA had a mild insulin sensitizing effect ( p < 0.05, slope of curve), increased plasma HDL cholesterol ( p < 0.05, +28%), reduced postprandial plasma TG ( p < 0.05), and showed protection from HFHC-induced changes to gut microbial composition in LBW pigs as compared to HFHC diet containing standard beef fat. This is the first study to show effects of natural trans fats on gut dysbiosis; further studies are needed to elucidate mechanisms.

Previous work has shown that dietary flaxseed can significantly reduce cardiac damage from a coronary artery ligation-induced myocardial infarction. However, this model uses healthy animals and the ligation creates the infarct in an artificial manner. The purpose of this study was to determine if dietary flaxseed can protect the hearts of JCR:LA-cp rats, a model of genetic obesity and metabolic syndrome, from naturally occurring myocardial ischemic lesions. Male and female obese rats were randomized into four groups (n = 8 each) to receive, for 12 weeks, either a) control diet (Con), b) control diet supplemented with 10% ground flaxseed (CFlax), c) a high-fat, high sucrose (HFHS) diet, or d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. In male obese rats, serum total cholesterol and LDL-C were significantly lower in CFlax compared to Con.  Obese rats on HFHS exhibited increased myocardial ischemic lesions and diastolic dysfunction regardless of sex. HFlax significantly lowered the frequency of cardiac lesions and improved diastolic function in male and female obese rats compared to HFHS. Blood pressures were similar in obese and lean rats. No aortic atherosclerotic lesions were detectable in any group. Collectively, this study shows that a HFHS diet increased myocardial ischemic lesion frequency and abolished the protective effect of female sex on cardiac function. More importantly, the data demonstrates dietary flaxseed protected against the development of small spontaneous cardiac infarcts despite the ingestion of a HFHS diet and the presence of morbid obesity., Competing Interests: Declaration of competing interests The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA- cp rat model of genetic obesity. Male and female obese rats were randomized into four groups ( n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA- cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum . Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

Introduction: Cardiovascular disease (CVD) originates in childhood and risk is exacerbated in obesity. Mechanisms of the etiologic link between early adiposity and CVD-risk remain unclear. Postprandial or non-fasting dyslipidemia is characterized by elevated plasma triglycerides (TG) and intestinal-apolipoprotein(apo)B48-remnants following a high-fat meal and is a known CVD-risk factor in adults. The aim of this study was to determine (a) whether the fasting concentration of apoB48-remnants can predict impaired non-fasting apoB48-lipoprotein metabolism (fat intolerance) and (b) the relationship of these biomarkers with cardiometabolic risk factors in youth with or without obesity., Methods: We assessed fasting and non-fasting lipids in youth without obesity (n = 22, 10 males, 12 females) and youth with obesity (n = 13, 5 males, 8 females) with a mean BMI Z-score of 0.19 ± 0.70 and 2.25 ± 0.31 (P = .04), respectively., Results: Fasting and non-fasting apoB48-remnants were elevated in youth with obesity compared to youth without obesity (apoB48: 18.04 ± 1.96 vs 8.09 ± 0.59, P < .0001, and apoB48 AUC : 173.0 ± 20.86 vs 61.99 ± 3.44, P < .001). Furthermore, fasting plasma apoB48-remnants were positively correlated with the non-fasting response in apoB48 AUC (r = 0.84, P < .0001) as well as other cardiometabolic risk factors including HOMA-IR (r = 0.61, P < .001) and leptin (r = 0.56, P < .0001)., Conclusion: Fasting apoB48-remnants are elevated in youth with obesity and predict apoB48 postprandial dyslipidemia. ApoB48-remnants are associated with the extent of fat intolerance and appear to be potential biomarker of CVD-risk in youth., (© 2020 World Obesity Federation.)

Ruminant meat (RM) is an excellent source of high-quality protein, B vitamins and trace minerals and plays an important role in global food and nutrition security. However, nutritional guidelines commonly recommend reduced intake of RM mainly because of its high saturated fatty acid (SFA) content, and more recently because of its perceived negative environmental impacts. RM is, however, rich in heart healthy cis-monounsaturated fatty acids and can be an important source of long-chain omega-3 (n-3) fatty acids in populations with low fish consumption. In addition, RM is a source of bioactive phospholipids, as well as rumen-derived bioactive fatty acids including branched-chain, vaccenic and rumenic acids, which have been associated with several health benefits. However, the role of bioactive RM lipids in maintaining and improving consumers' health have been generally ignored in nutritional guidelines. The present review examines RM lipids in relation to human health, and evaluates the effectiveness of different feeding strategies and possibilities for future profile and content improvement., Competing Interests: Declaration of Competing Interest None., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Cardiovascular disease (CVD) begins in youth, and is exacerbated by obesity and metabolic syndrome. Apolipoprotein (Apo)B-remnant cholesterol is considered a primary contributor to CVD risk. Fasting plasma apoB48 can be used as a biomarker of intestinal remnant cholesterol as well as postprandial dyslipidemia. In adults, elevated fasting plasma apoB48 strongly associates with cardiometabolic risk factors and obesity, whereas in adolescents there is limited data. The aim of this study was to measure fasting plasma apoB48 and determine the relationship with cardiometabolic risk factors in adolescents., Methods: This is a cross-sectional study of fasting plasma apoB48 from the Western Australian Pregnancy Cohort (Raine) Study. Subjects were adolescent males and females aged 17 years with complete fasting plasma apoB48, biochemical, and anthropometry data (n = 1045). The relationship between fasting plasma apoB48 and other cardiometabolic risk factors was determined. The high-risk metabolic cluster variable was defined using elevated BMI, HOMA-IR, fasting plasma triglycerides, and systolic blood pressure., Results: Fasting plasma apoB48 was significantly higher in male (15.28 ± 2.95 μg/mL) compared to female (12.45 ± 2.43 μg/mL) adolescents (p = 0.0003), and was increased by 21% (3.60 μg/mL; p = 0.0000) in the high-risk metabolic cluster group and more pronounced in males (31%, 6.15 μg/mL; p = 0.0000). Fasting plasma apoB48 was positively associated with fasting plasma triglycerides, total-cholesterol (but not LDL-C), insulin, leptin, HOMA-IR, and the anthropometric parameters, waist-circumference and skinfold-thickness. Fasting plasma apoB48 was inversely associated with fasting plasma HDL-C, and adiponectin., Conclusions: Plasma apoB48 remnant lipoproteins associate with cardiometabolic risk factors in adolescents and provide support for the screening of remnant cholesterol in youth., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Context: Adolescents with polycystic ovary syndrome (PCOS) have increased incidence of cardiometabolic risk factors including dyslipidemia. Atherogenic apolipoprotein (apo) B-lipoprotein remnants are associated with increased cardiovascular disease (CVD) risk., Objective: The aim of this study was to determine the concentrations of fasting plasma apoB-lipoprotein remnants, apoB48 and apoB100, and their association with cardiometabolic risk factors and androgen indices in adolescent girls with and without PCOS., Design Setting and Participants: Participants (n = 184) aged 17 years were recruited in the Menstruation in Teenagers Study from the Western Australian Pregnancy Cohort (Raine) Study., The Main Outcome Measures: Fasting plasma apo-B48 and -B100 lipoprotein remnant concentrations in adolescent girls with and without PCOS., Results: Fasting plasma apoB48-lipoprotein remnants but not apoB100-lipoprotein remnants were elevated in adolescent girls with increased cardiometabolic risk compared with those with lower cardiometabolic risk (13.91 ± 5.06 vs 12.09 ± 4.47 µg/mL, P < .01). ApoB48-lipoprotein remnants were positively correlated with fasting plasma triglycerides (b = .43, P < .0001). The prevalence of increased cardiometabolic risk factors was 2-fold higher in those diagnosed with PCOS (35.3%) than in those without PCOS (16.3%). Conclusion: Adolescents with PCOS have a 2-fold higher incidence of cardiometabolic risk factors than those without PCOS. Fasting apoB48-lipoprotein remnants are elevated in adolescent girls with a high prevalence of cardiometabolic risk factors., (© Endocrine Society 2020.)

Low birth weight (LBW) and postnatal nutrition are risk factors for adult metabolic diseases. However, the interactions between LBW, diet, and intestinal lipid absorption and secretion leading to adult metabolic disease remain unclear. The current study determined the impact of LBW on intestinal lipid and carbohydrate metabolism under both control and Western diet (high fat, high fructose, and cholesterol) conditions in 5-wk-old LBW and normal birth weight (NBW) Landrace-Large White × Duroc pigs. A 2-step modified oral glucose and fat challenge test was performed. Mesenteric lymph, jejunal mucosal scrapings, and cecal digesta samples were also collected. LBW offspring were lower in weight and gained less weight per day. LBW pigs on either control or Western diets displayed increased triglyceride (TG) secretion into lymph ( P = 0.0135). Western diet-fed LBW pigs developed fasting ( P = 0.03) and postprandial ( P < 0.05) hypertriglyceridemia, muscle steatosis ( P = 0.0072), had higher insulin excursion ( P < 0.01), increased jejunal stearoyl-CoA desaturase 1 mRNA and increased hepatic fibrosis ( P = 0.0017) compared with NBW piglets. Gut microbiota showed significant dysbiosis on Western diet independent of birth weight. In conclusion, LBW pigs fed a Western diet specifically up-regulate TG absorption and secretion, develop dyslipidemia, muscular steatosis, and display early signs of insulin resistance. Interestingly, this study does not provide evidence of altered intestinal microbiome in LBW pigs contributing to increased severity of metabolic diseases.-Fontaine, M. A., Diane, A., Singh, V. P., Mangat, R., Krysa, J. A., Nelson, R., Willing, B. P., Proctor, S. D. Low birth weight causes insulin resistance and aberrant intestinal lipid metabolism independent of microbiota abundance in Landrace-Large White pigs.

Agents that block the renin-angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague-Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.

The intestine is involved in whole-body lipid and cholesterol homeostasis and secretes lipoproteins containing apolipoprotein (Apo)B48 and discrete ApoA-I into the mesenteric lymph. The lymphatic system has been proposed to have a significant role in the reverse cholesterol transport pathway associated with HDL-ApoA-I. In conditions of insulin resistance (IR), there is intestinal overproduction of chylomicrons containing ApoB48; however, there is limited data on the intestinal synthesis and secretion of HDL-ApoA-I. microRNA (miR)-223 has been shown to regulate peripheral HDL metabolism and may impact intestinal-derived HDL. Niacin (nicotinic acid; vitamin B3) is known to regulate lipid metabolism, but the role of niacin in modulating intestinal lipid and lipoprotein (ApoB48 and ApoA-I) metabolism is unknown. The aim of this study was to determine the secretion of intestinal lymphatic HDL-ApoA-I and the effect of dietary intervention with niacin on these pathways in a rodent model of IR. HDL was isolated from intestinal mesenteric lymph by density ultracentrifugation, and subsequent HDL miR analysis was developed in collaboration with Exiqon Services. Insulin-resistant rodents were fed chow or chow with niacin (1% w/w) for 6 wk. Intestinal lymph HDL-ApoA-I and miR-223 expression were lower by at least 45 and 60%, respectively, and lymph HDL was associated with 85% higher triglyceride (TG) content in IR compared to non-IR control group. Niacin was found to increase secretion of lymph HDL and miR-223 by at least 50-60% and to deplete the TGs associated with HDL compared with the nontreated IR group. Niacin significantly increased peroxisome proliferator-activating nuclear receptor α and carnitine palmitoyltransferase I α mRNA and annulled Tnf-α mRNA expression in intestinal (jejunal) explants. Altered intestinal lymphatic HDL-ApoA-I and miR-223 metabolism in IR and modulation by niacin may provide insight into the intestinal-mediated regulation of the reverse cholesterol transport pathway.-Mangat, R., Borthwick, F., Haase, T., Jacome, M., Nelson, R., Kontush, A., Vine, D. F., Proctor, S. D. Intestinal lymphatic HDL miR-223 and ApoA-I are reduced during insulin resistance and restored with niacin.

The objective of the present experiment was to determine if carcass quality and fatty acid profiles of longissimus thoracis (LT) and hamburger would be affected by feeding steers extruded flaxseed on its own followed by hay (non-TMR) compared to when hay and extruded flaxseed were fed together (TMR). Forty-eight steers in six pens were assigned to TMR or non-TMR for an average of 242days. Dry matter intake was lower for non-TMR versus TMR steers (10.56 vs. 11.42kg/d; P=0.02), but final live weight (610±0.50kg) and average daily gain (1.18±0.02kg/d) did not differ. Compared to TMR, feeding non-TMR enriched LT and hamburger with α-linolenic acid (ALA; 18:3n-3) by 14%, vaccenic acid (VA; t11-18:1) by 44%, rumenic acid (RA; c9,t11-18:2) by 40%, and conjugated linolenic acid (CLnA) by 58%. Overall, feeding extruded flaxseed separately from hay in a non-TMR was more effective at enhancing deposition of ALA, VA, RA and CLnA in beef., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Context: Proprotein convertase subtilisin kexin 9 (PCSK9) mediates degradation of the low-density lipoprotein receptor (LDLR), thereby increasing plasma low-density lipoprotein cholesterol (LDL-C). Variations in the PCSK9 gene associated with loss of function (LOF) of PCSK9 result in greater expression of hepatic LDLR, lower concentrations of LDL-C, and protection from cardiovascular disease (CVD). Apolipoprotein-B (apoB) remnants also contribute to CVD risk and are similarly cleared by the LDLR. We hypothesized that PCSK9-LOF carriers would have lower fasting and postprandial remnant lipoproteins on top of lower LDL-C., Objective: To compare fasting and postprandial concentrations of triglycerides (TGs), total apoB, and apoB48 as indicators of remnant lipoprotein metabolism in PCSK9-LOF carriers with those with no PCSK9 variants., Design: Case-control, metabolic study., Setting: Clinical Research Center of The Ottawa Hospital., Participants: Persons with one or more copies of the L10ins/A53V and/or I474V and/or R46L PCSK9 variant and persons with no PCSK9 variants., Intervention: Oral fat tolerance test., Main Outcomes Measures: Fasting and postprandial plasma TG, apoB48, total apoB, total cholesterol, and PCSK9 were measured at 0, 2, 4, and 6 hours after an oral fat load., Results: Participants with PCSK9-LOF variants (n = 22) had reduced fasting LDL-C (-14%) as well as lower fasting TG (-21%) compared with noncarrier controls (n = 23). LOF variants also had reduced postprandial total apoB (-17%), apoB48 (-23%), and TG (-18%). Postprandial PCSK9 declined in both groups (-24% vs -16%, respectively)., Conclusions: Participants carrying PCSK9-LOF variants had attenuated levels of fasting and postprandial TG, apoB48, and total apoB. This may confer protection from CVD and further validate the use of PCSK9 inhibitors to lower CVD risk., (Copyright © 2017 Endocrine Society)

The present study was designed to determine if feeding steers extruded flaxseed and hay (25 and 75%; DM basis) together as a total mixed ration (TMR), or sequentially (non-TMR) would result in different enrichments of polyunsaturated fatty acids (PUFA) and their biohydrogenation intermediates (BHI) in beef adipose tissues [subcutaneous (SC) vs perirenal (PR) fat]. Forty-eight Angus cross steers (325 ± 16 kg) were stratified by weight to six pens, and pens were randomized to either TMR or non-TMR and fed ad libitum for an average of 242 days. The concentrations of α-linolenic acid increased by 18 mol% in both SC and PR in non-TMR steers compared to TMR steers (P < 0.01). trans 18:1 isomers were more concentrated in PR than SC (14.4 vs 9.5 mol%; P < 0.01) and increased by 10 mol% in both fat depots for non-TMR (P < 0.01). Other BHI including non-methylene-interrupted 18:2 (atypical dienes), conjugated linoleic acids and conjugated linolenic acids (CLnA) were affected by diet × tissue interactions (P < 0.01). The CLnA and CLA contents were higher in both fat depots when feeding the non-TMR, but the effect of diet was more pronounced in PR than in SC (P < 0.01). Atypical dienes were highest in PR from non-TMR and lowest in TMR fed steers (4.3 and 3.6 mol%) with SC contents being intermediate. The sequential feeding of lipid supplement can thus profoundly affect the enrichment of PUFA and their BHI in beef fat and their differentially enrichment is also fat depot dependant.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease involved in the regulation of LDL receptor (LDLR) expression and apolipoprotein B lipoprotein cholesterol metabolism. Hepatic PCSK9 protein expression, activity, and secretion have been shown to affect cholesterol homeostasis. An upregulation of hepatic PSCK9 protein leads to increased LDLR degradation, resulting in decreased uptake of apoB lipoproteins and a consequent increase in the plasma concentration of these lipoproteins, including LDL and chylomicron remnants. Hence, PCSK9 has become a novel target for lipid-lowering therapies. The aim of this review is to outline current findings on the metabolic and dietary regulation of PCSK9 and effects on cholesterol, apoB lipoprotein metabolism, and cardiovascular disease (CVD) risk. PCSK9 gene and protein expression have been shown to be regulated by metabolic status and the diurnal pattern. In the fasting state, plasma PCSK9 is reduced via modulation of the nuclear transcriptional factors, including sterol regulatory element-binding protein (SREBP) 1c, SREBP2, and hepatocyte nuclear factor 1α. Plasma PCSK9 concentrations are also known to be positively associated with plasma insulin and homeostasis model assessment of insulin resistance, and appear to be regulated by SREBP1c independently of glucose status. Plasma PCSK9 concentrations are stable in response to high-fat or high-protein diets in healthy individuals; however, this response may differ in altered metabolic conditions. Dietary n-3 polyunsaturated fatty acids have been shown to reduce plasma PCSK9 concentration and hepatic PCSK9 mRNA expression, consistent with their lipid-lowering effects, whereas dietary fructose appears to upregulate PCSK9 mRNA expression and plasma PCSK9 concentrations. Further studies are needed to elucidate the mechanisms of how dietary components regulate PCSK9 and effects on cholesterol and apoB lipoprotein metabolism, as well as to delineate the clinical impact of diet on PCSK9 in terms of CVD risk., (© 2017 American Society for Nutrition.)

Context: Adolescents with polycystic ovary syndrome (PCOS) have atherogenic dyslipidemia and increased cardiovascular disease (CVD) risk, and this is exacerbated in obesity., Objective: To determine and compare fasting and nonfasting lipid and apolipoprotein (Apo)B-lipoprotein metabolism in 3 groups of adolescent girls: healthy-weight controls, obese without PCOS (obese-control), and obese with PCOS (obese-PCOS)., Design, Setting, and Participants: Participants aged 12 to 17 years were recruited for this cross-sectional study from a pediatric weight management clinic and the local community in Alberta, Canada., Main Outcome Measures: Plasma lipids and ApoB lipoproteins, including triglycerides (TGs) and ApoB100- and ApoB48-lipoproteins, were measured in the fasted and postprandial state following a high-fat meal., Results: Obese-control (n = 12) and obese-PCOS (n = 18) groups had twofold higher concentrations of fasting plasma TG and ApoB100- and ApoB48-lipoprotein remnants compared to healthy-weight controls (n = 10) (ApoB48-lipoproteins: 19.32 ± 2.10, 24.02 ± 4.28, and 8.95 ± 1.05 μg/mL, respectively; P < 0.001). The obese-PCOS group had 50% higher fasting plasma TG level compared to the obese-control group. The postprandial response was higher in both obese-controls and obese-PCOS subjects compared with healthy-weight controls in plasma TG area under the curve (AUC) (1028.0 ± 83.67, 1587.01 ± 259.6, and 615.42 ± 76.42 μg/mL⋅h, respectively; P < 0.01) and ApoB48(AUC) (191.30 ± 19.06, 238.8 ± 37.73, and 96.58 ± 9.17 μg/mL⋅h, respectively; P < 0.0001). Nonfasting plasma TG(AUC) and ApoB48(AUC) were positively correlated with free testosterone (r = 0.38; P < 0.001 and r = 0.33; P < 0.05, respectively), and these relationships were highly associated with insulin and body mass index., Conclusions: Adolescent girls with obesity and PCOS have elevated fasting and postprandial plasma TG and ApoB-lipoprotein remnants, providing evidence of early subclinical CVD risk, and these indices are highly associated with impaired insulin metabolism and hyperandrogenemia., (Copyright © 2017 by the Endocrine Society)

Obesity and its metabolic complications have emerged as the epidemic of the new millennia. The use of obese rodent models continues to be a productive component of efforts to understand the concomitant metabolic complications of this disease. In 1978, the JCR:LA-cp rat model was developed with an autosomal recessive corpulent ( cp ) trait resulting from a premature stop codon in the extracellular domain of the leptin receptor. Rats that are heterozygous for the cp trait are lean-prone, while those that are homozygous ( cp/cp ) spontaneously display the pathophysiology of obesity as well as a metabolic syndrome (MetS)-like phenotype. Over the years, there have been formidable scientific contributions that have originated from this rat model, much of which has been reviewed extensively up to 2008. The premise of these earlier studies focused on characterizing the pathophysiology of MetS-like phenotype that was spontaneously apparent in this model. The purpose of this review is to highlight areas of recent advancement made possible by this model including; emerging appreciation of the "thrifty gene" hypothesis in the context of obesity, the concept of how chronic inflammation may drive obesogenesis, the impact of acute forms of inflammation to the brain and periphery during chronic obesity, the role of dysfunctional insulin metabolism on lipid metabolism and vascular damage, and the mechanistic basis for altered vascular function as well as novel parallels between the human condition and the female JCR:LA-cp rat as a model for polycystic ovary disease (PCOS).

Hawthorn is a widely used herbal alternative medicine for the treatment of various cardiovascular diseases. However, the attributed health benefits, purported to be due to the presence of phenolic compounds, may depend on both the specific species and plant part. Studies to date investigating effects of hawthorn on heart disease(s) have used well-described European and/or Asian species, while little is known regarding the bioactivity of species native to North America. Six weeks of supplementation of both fireberry hawthorn berry (native Crataegus chrysocarpa) and English hawthorn leaf (C. monogyna, naturalized in North America) in the JCR:LA-cp rat, resulted in a significant reduction in heart weight, fasting LDL-C and improved heart function (p < 0.05). Fasting triglyceride and myocardial fibrosis were also reduced, but only by the berry extract. We demonstrate that both of the Canadian-sourced hawthorn extracts (introduced leaf and native berry) have cardioprotective benefits, likely via increased availability of nitric oxide.

Over the past 20 years, a growing amount of evidence supports the role of microbes and an imbalanced microbiota in inflammatory bowel disease (IBD). While many reviews have been written on the microbiota in IBD, few have considered how they fulfil the Koch's postulates. In this review, we consider how the Koch's postulates might be modified so that they can be fulfilled for polymicrobial diseases, and we discuss the progress made to date in fulfilling them., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Context: Atherosclerotic vascular disease begins in childhood and while progression is multifactorial, obesity in early life is an important risk factor for its development., Objective: To determine whether fasting apoB48 remnant lipoproteins (relative to classic lipid markers), is elevated with increasing central adiposity over time in a cohort of Canadian children with a family history of obesity., Design: Data were drawn from the ongoing prospective cohort of 630 Caucasian families in Québec, Canada, recruited to assess determinants and effects of childhood obesity (Québec Adiposity and Lifestyle Investigation in Youth [QUALITY]cohort)., Participants: Children who attended baseline and first followup clinic visits (n =570; age 9.6 y)., Main Outcome Measure: Trunk fat mass was determined by dual energy x-ray absorptiometry. Central fat mass index was calculated as CFMI = trunk fat mass/height(2) (kg/m(2)) and groups created (CFMI <1.5; 1.5-3.0; ≥3.0 kg/m(2)) to suggest lower, moderate, or higher central adiposity. Changes over time in outcomes (apoB48, triglyceride and total, low-, and high-density lipoprotein cholesterol) were compared using paired t test and multiple regression that adjusted for age, sex, and Tanner stage., Results: Classic lipid markers (total and low-density lipoprotein cholesterol) improved at followup, whereas apoB48 became worse (increased). ApoB48 increased with increasing central adiposity, highest (37%) in children who transitioned from lower- to moderate-CFMI groups (ΔapoB48 = 1.5 μg/mL). For every 1 kg/m(2) increase in central adiposity over the 2-y period, an increase in apoB48 was 14-fold greater among children with lower baseline CFMI, compared with higher CFMI., Conclusions: Increased fasting concentrations of apoB48 may be representative of changes in adiposity at lower levels of central fat (early periods of risk).

The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats.

Vaccenic acid (VA), the predominant ruminant-derivedtransfat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cprats were assigned to a control diet with or without VA (1% w/w),cis-9,trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2-AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P< 0.001), but did not change AA in tissue PLs. There was no additive effect of combining VA+CLA on 2-AG relative to VA alone (P> 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P< 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFα and interleukin 1β (P< 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine., (Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.)

Scope: Trans-11 vaccenic acid (VA) is a fatty acid produced by ruminants entering the human food supply through meat and dairy products, which appears not to have the health risks associated with industrially produced trans-fatty acids. In this study, we investigated the effect of VA on insulin secretion in vivo in rats and in vitro in human and rat islets after diabetogenic insult., Methods and Results: Hyperglycemic clamp showed that VA dietary supplementation for 8 weeks significantly increased glucose turnover in rats with type 2 diabetes (T2D), accompanied by an elevated plasma C-peptide concentration, indicating improved insulin secretion. The β-cell area and proliferation rate were higher in T2D+VA than T2D group. Isolated islets from T2D+VA rats had higher glucose-stimulated insulin secretion (GSIS) than T2D group. In vitro, VA treatment for 24 and 48 h significantly enhanced GSIS in rat and human islets after diabetogenic challenges. The mRNA expression of G-protein-coupled receptor 40 (GPR40) and regenerating islet-derived 1α (REG-1α) were consistently increased by VA in both rat and human islets., Conclusion: These results indicate that VA may improve insulin secretion and growth of islets in T2D, at least partly by altering GPR40 and REG-1α mRNA expression., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Catheterization of the intestinal lymph trunk in neonatal pigs is a technique allowing for the long-term collection of large quantities of intestinal (central) efferent lymph. Importantly, the collection of central lymph from the intestine enables researchers to study both the mechanisms and lipid constitutes associated with lipid metabolism, intestinal inflammation and cancer metastasis, as well as cells involved in immune function and immunosurveillance. A ventral mid-line surgical approach permits excellent surgical exposure to the cranial abdomen and relatively easy access to the intestinal lymph trunk vessel that lies near the pancreas and the right ventral segment of the portal vein underneath the visceral aspect of the right liver lobe. The vessel is meticulously dissected and released from the surrounding fascia and then dilated with sutures allowing for insertion and subsequent securing of the catheter into the vessel. The catheter is exteriorized and approximately 1 L/24 hr of lymph is collected over a 7 day period. While this technique enables the collection of large quantities of central lymph over an extended period of time, the success depends on careful surgical dissection, tissue handling and close attention to proper surgical technique. This is particularly important with surgeries in young animals as the lymph vessels can easily tear, potentially leading to surgical and experimental failure. The video demonstrates an excellent surgical technique for the collection of intestinal lymph.

White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin-dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.