Search

Background Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n-3) polyunsaturated fatty acids (LCn-3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment. Objectives The objective of this study was to measure the relation of erythrocyte LCn-3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer. Methods This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I-III). Erythrocyte LCn-3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models. Results The ω-3 index, a measurement of LCn-3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (β = 0.015, P = 0.01) and grip strength (β = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness. Conclusions The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn-3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors.

Short-term (3-day) consumption of a high fat diet (HFD) rich in saturated fats is associated with a neuroinflammatory response and subsequent cognitive impairment in aged, but not young adult, male rats. This exaggerated effect in aged rats could be due to a “primed” microglial phenotype observed in the normal aging process in rodents in which aged microglia display a potentiated response to immune challenge. Here, we investigated the impact of HFD on microglial priming and lipid composition in the hippocampus and amygdala of young and aged rats. Furthermore, we investigated the microglial response to palmitate, the main saturated fatty acid (SFA) found in HFD that is proinflammatory. Our results indicate that HFD increased gene expression of microglial markers of activation indicative of microglial priming, including CD11b, MHCII, CX3CR1, and NLRP3, as well as the pro-inflammatory marker IL-1β in both hippocampus and amygdala-derived microglia. Furthermore, HFD increased the concentration of SFAs and decreased the concentration of polyunsaturated fatty acids (PUFAs) in the hippocampus. We also observed a specific decrease in the anti-inflammatory PUFA docosahexaenoic acid (DHA) in the hippocampus and amygdala of aged rats. In a separate cohort of young and aged animals, isolated microglia from the hippocampus and amygdala exposed to palmitate in vitro induced an inflammatory gene expression profile mimicking the effects of HFD in vivo. These data suggest that palmitate may be a critical nutritional signal from the HFD that is directly involved in hippocampal and amygdalar inflammation. Interestingly, microglial activation markers were increased in response to HFD or palmitate in an age-independent manner, suggesting that HFD sensitivity of microglia, under these experimental conditions, is not the sole mediator of the exaggerated inflammatory response observed in whole tissue extracts from aged HFD-fed rats.

OBJECTIVES: Compare the effects of high-fat diets containing linoleic-acid (LA)-rich oil and lard on measures of whole-body energy metabolism and skeletal muscle function in a mouse model of diet-induced obesity. METHODS: 9-week old male C57BL6/J mice (n = 24) were assigned to high fat isocaloric diets (24% fat by wt) containing LA-rich safflower oil (SO) or lard (LD) for 18 weeks. Food intake and body weight were measured every 2 days. EchoMRI was used at Days 0, 65, and 100 to determine the effects of each diet on body composition. Grip strength was measured to assess muscle strength at Day 113. Fasting blood glucose was measured and an insulin tolerance test (ITT) was performed on Day 85 to measure insulin sensitivity and glucose uptake. After 130 days, quadriceps muscle mitochondrial and cardiolipin remodeling gene expression was measured by qRT-PCR. Cardiolipin (CL) speciation of muscle was measured by normal phase liquid chromatography coupled to electrospray ionization mass spectrometry. RESULTS: Although LD-fed mice gained body mass at a faster rate, there was no difference in body mass or cumulative food intake after 130 days. Similarly, % adiposity of LD-fed mice increased at Day 65 compared to those fed the SO diet, but not at Day 100. Mice consuming the SO diet exhibited increased hindlimb grip strength. SO-fed mice exhibited lower blood glucose levels at 90 and 120 minutes post-insulin injection, demonstrating improved glucose clearance over time. Significant differences in CL speciation, particularly that of LA-containing species, were observed. CONCLUSIONS: When compared to the LD diet, mice consuming the SO diet exhibited early reductions in adiposity that were undistinguishable after 130 days of dietary intervention. However, mice fed SO diet exhibited improved grip strength, insulin-stimulated glucose clearance and significant differences in skeletal muscle cardiolipin speciation. Future studies will address the relationship between LA-derived metabolites, CL speciation, and improved muscle function. FUNDING SOURCES: Funding was provided by NIH, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship. DBS received support from the AOCS Thomas H. Smouse Memorial Fellowship.

OBJECTIVES: Investigate the impact of LA-rich oil (LO) on measures of energy metabolism in a mouse model of metabolic syndrome. METHODS: Ob/ob mice were fed diets containing 6% wt LO, oleic acid-rich (OO) or palmitic acid-rich (PO) for 6 weeks. Body composition was measured at weeks 0 and 6. Plasma was collected at necropsy to measure adiponectin, insulin, and glucose. Grip strength and muscle fiber cross-sectional area (CSA) of total and succinate dehydrogenase-positive (SDH) fibers were quantified in quadriceps. In white adipose tissue, mRNA was measured for markers of beiging and lipid storage. RESULTS: Mice fed OO and LO diets (vs. PO diet) had reduced % adipose. There was no difference of oils on plasma adiponectin or HOMA-IR. Decreases in grip strength were observed in PO-fed mice, while OO and LO-fed mice maintained strength throughout the study. LO-fed mice exhibited smaller skeletal muscle fibers compared to the PO-fed mice. OO-fed mice had fewer intermediate-sized SDH fibers. In white adipose tissue, LO-fed mice exhibited increased PGC1a, and decreased PPARy and LPL mRNA compared to PO-fed mice. CONCLUSIONS: These findings suggest that dietary LA may alter lipid mobilization and metabolism in obese mice. These preliminary results showcase the importance of future investigation of lipid storage and mitochondrial phospholipid biology in skeletal muscle. FUNDING SOURCES: Funding was provided by NIH R21CA185140, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship. DBS received support from the AOCS Thomas H. Smouse Memorial Fellowship.

OBJECTIVES: Due to the established cardioprotective effects of fish oil in pressure-induced models of heart failure, we hypothesize that fish oil could also be cardioprotective in anthracycline-induced heart failure. METHODS: In a mouse model of anthracycline cardiotoxicity male mice were assigned to one of four groups: anthracycline injection + control diet, saline injection + control diet, anthracycline injection + fish oil diet, or saline injection + fish oil diet. The control diet contained 90 g/kg soybean oil while the fish oil diet contained 40 g/kg soybean oil and 50 g/kg fish oil (8% fat by weight). The differences between groups were assessed by two-way ANOVA. Sidak's multiple comparison test was used to determine differences from the control group. RESULTS: Controlling for body weight, anthracycline treatment increased heart weight in both diet groups suggesting cardiac hypertrophy. Compared with control diet, fish oil diet attenuated anthracycline-induced increases in pro-inflammatory Il6 and pro-fibrotic collagen III mRNA. In addition, dietary fish oil increased bcl2 (anti-apoptosis) and heme oxygenase-1 (antioxidant) mRNA in heart muscle in mice treated with anthracycline. CONCLUSIONS: Our data suggest that dietary fish oil may attenuate some of the cardiotoxic effects of anthracyclines. Fish oil is generally found to be safe in cancer patients, and if effective in clinical trials could provide a widely available therapy for cancer patients undergoing anthracycline chemotherapy. FUNDING SOURCES: Funding was provided by NIH R21CA185140, Ohio Agriculture Research and Development Center, the Carol S. Kennedy Professorship, and the Ohio State University Education and Human Ecology Dissertation Research Fellowship.

OBJECTIVES: Higher blood levels of the essential fatty acid, linoleic acid (LA), are associated with a decreased risk of type 2 diabetes. However, many dietary oils once high in LA are now low in LA and high in oleic acid (OA). We have previously shown in healthy adults that supplementation with a high LA oil can increase plasma LA levels and decrease plasma OA levels. The current study examines the relationship of habitual levels of plasma LA and OA with markers of body composition, inflammation and glycemia in healthy adults. METHODS: Data from baseline visit were analyzed from 127 health adults participating in a 2-week study of the effect of dietary oils on blood fatty acid profiles. Plasma fatty acid composition was measured by gas chromatography. Insulin, glucose, total and high molecular weight (HMW) adiponectin, tumor necrosis factor receptor 2 (TNF-r2) and lipopolysaccharide binding protein (LBP) were measured in fasting plasma samples. Body mass index (BMI) and sagittal diameter (SAD) were measured as markers of body composition. Grip strength was measured as a marker of muscle strength and gait speed was measured as a marker of muscle function. Linear regression was used to assess the association of study measurements to plasma LA or OA. Results were adjusted for sex, age, physical activity and BMI. RESULTS: Plasma LA was negatively associated with both BMI and SAD while plasma OA was positively associated with both insulin and grip strength. In males, but not females, higher plasma LA was associated with higher HMW adiponectin while higher plasma OA was positively associated with fasting glucose. Neither plasma LA or OA were associated with total adiponectin, TNF-r2, LBP or gait speed. CONCLUSIONS: Higher levels of plasma LA predicted for lower measures of adiposity in both males and females and higher HMW adiponectin levels in males. Higher levels of plasm OA predicted for increased grip strength and higher glycemia, particularly in men. To our knowledge no randomized controlled trial has compared LA or OA supplementation on body composition, glycemia, and adiponectin in healthy men and women. FUNDING SOURCES: Funding was provided by the Carol S. Kennedy Professorship and the Ohio Agriculture Research and Development Center.

OBJECTIVES: Investigate the impact of dietary linoleic acid (LA) on whole-body energy metabolism, fatty acid uptake, oxylipin metabolites, and energy production machinery in skeletal muscle. METHODS: Mice were fed modified AIN-93 M diets containing 6% wt of LA or palmitic acid (PA) for 5 weeks. To address energy balance, grip strength, blood glucose, and body composition were measured weekly and indirect calorimetry was performed after 4.5 weeks of diet. To address skeletal muscle architecture, cross-sectional area was quantified in quadriceps. To determine the effect of LA diet on skeletal muscle lipids, fatty acid composition was measured in quadriceps using GC. Targeted lipidomics using LC-MS/MS was utilized to measure LA-derived oxylipins in mitochondria isolated from gastrocnemius. RESULTS: No difference in food intake, body weight, blood glucose, or body composition were observed between diet groups. Mice fed the LA diet exhibited higher heat production and lower respiratory exchange ratio, independent of ambulatory activity compared to mice fed the PA diet. Cross sectional area analysis in quadriceps muscle revealed that mice fed the LA diet had smaller muscle fibers compared to mice fed the PA diet. The LA diet increased LA level in quadriceps. Using hierarchal cluster analysis, we identified several unique patterns of oxylipins that impact insulin sensitivity and may be associated with increased mitochondrial capacity. Mice fed the LA diet exhibited a three-fold increase of oxylipin metabolites 9- and 13-HODE, and 12,13-diHOME. CONCLUSIONS: Mice fed a diet fortified in LA have increased LA in skeletal muscle, changes to skeletal muscle architecture, favorable changes to whole body energy metabolism, and increases in LA-derived oxylipins in skeletal muscle mitochondria. Our discovery that LA generates 9-HODE and 13-HODE in muscle mitochondria suggests that downstream pathways, including PPARg transactivation, may be linked with effects on muscle energy metabolism. FUNDING SOURCES: Funding was provided by the National Institutes of Health (NIH) R21CA185140, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship. DBS is supported by the Center for Muscle Health and Neuromuscular Disorders Predoctoral Research Fellowship.

Summary Background & aims Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood. The study objective was to evaluate effects of conjugated linoleic acid (CLA) and safflower (SAF) oils on glycemia, blood lipids, and inflammation. The hypothesis we tested is that dietary oils improve glycemia, lipids, and inflammatory markers in a time-dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils. Methods Fifty-five post-menopausal, obese women with type 2 diabetes enrolled, and 35 completed this randomized, double-masked crossover study. Treatments were 8 g daily of CLA and SAF for 16 weeks each. We used a multiple testing procedure with pre-determined steps analysis to determine the earliest time that a significant effect was detected. Results CLA did not alter measured metabolic parameters. SAF decreased HbA1c (−0.64 ± 0.18%, p = 0.0007) and C-reactive protein (−13.6 ± 8.2 mg/L, p = 0.0472), increased QUICKI (0.0077 ± 0.0035, p = 0.0146) with a minimum time to effect observed 16 weeks after treatment. SAF increased HDL cholesterol (0.12 ± 0.05 mmol/L, p = 0.0228) with the minimum time to detect an effect of SAF at 12 weeks. The minimum time to detect an increase of c9t11-CLA, t10c12-CLA, and linoleic acid in serum of women supplemented CLA or SAF, respectively, was four weeks. Conclusions We conclude that 8 g of SAF daily improved glycemia, inflammation, and blood lipids, indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications.

Objective Mechanistic pathways linking maternal long-chain polyunsaturated fatty acid (LC-PUFA) status with gestational length are poorly delineated. Key LC-PUFAs implicated in this association are the antiinflammatory omega-3 docosahexaenoic acid (DHA) and proinflammatory omega-6 arachidonic acid (AA). We hypothesized that (1) lower red blood cell (RBC) DHA:AA ratios would predict shorter gestation and (2) this effect would be mediated by both inflammation and sleep quality. Methods Pregnant women (n = 135) provided blood and completed the Pittsburg Sleep Quality Index at 20–27 weeks gestation. RBC fatty acids were determined by gas chromatography and serum inflammatory markers (IL-6, IL-8, TNF- α , IL-1 β , CRP) were determined by high-sensitivity ELISA. Results Lower DHA:AA ratios predicted higher serum IL-8 (r = −0.20, p = 0.02) and poorer sleep quality (b = −13.8, p = 0.02). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. Mediational analyses demonstrated indirect effects linking lower RBC DHA:AA with shorter gestation via higher IL-8 (95% CI = 0.10, 3.84) and poor sleep (95% CI = 0.35, 3.99). A significant race X DHA:AA interaction in predicting preterm birth (PTB) was observed (p = 0.049); among African Americans only, the odds of PTB decreased significantly as DHA:AA increased (OR for 0.1 unit increase = 0.25 (95% CI = 0.06, 0.99, p = 0.048). Discussion These data support both inflammatory pathways and sleep quality as significant mediators linking maternal DHA:AA status and length of gestation. African Americans may be at greater risk for PTB related to suboptimal DHA levels.