No abstract

Cachexia is responsible for nearly 20% of all cancer-related deaths, yet effective therapies to prevent or treat the disease are lacking. Clinical studies have shown that male patients lose weight at a faster rate than females. Additionally, an ‘obesity paradox’ may exist where excess adiposity may confer survival to patients with cancer cachexia. To further explore these phenomena, the aim of this study was to evaluate the role of changes of adipose tissue mass, sex status, and tumor mass on outcomes of male, female and ovariectomized (OVX) mice with C-26 adenocarcinoma-induced cachexia. We used EchoMRI to assess body composition and grip strength to measure muscle function. Body weights and food intake were measured daily. Mice were euthanized 19 days post-inoculation. Post-necropsy, muscle fiber cross-sectional areas were quantified and real-time PCR was performed for genes relating to proteolysis. Survival curve, correlation and multiple linear regression analyses were performed to identify predictors of cachexia. Female and OVX tumor mice developed cachexia similarly to males, as evidenced by loss of skeletal and adipose masses, decreased grip strength, and increased proteolytic gene expression. Notably, female and OVX tumor mice had earlier onset of cachexia (≥5% weight loss) than male tumor mice. Larger tumor mass and lower adipose mass were the strongest predicting factors for increased severity of cachexia, regardless of sex or ovariectomy status. These results indicated that the impact of sex status may be subtle in comparison to the predictive effect of tumor and adipose mass in mice with C-26-induced cachexia.

Polyunsaturated fats are energy substrates and precursors to the biosynthesis of lipid mediators of cellular processes. Adipose tissue not only provides energy storage, but influences whole-body energy metabolism through endocrine functions. How diet influences adipose–lipid mediator balance may have broad impacts on energy metabolism. To determine how dietary lipid sources modulate brown and white adipose tissue and plasma lipid mediators, mice were fed low-fat (15% kcal fat) isocaloric diets, containing either palm oil (POLF) or linoleate-rich safflower oil (SOLF). Baseline and post body weight, adiposity, and 2-week and post fasting blood glucose were measured and lipid mediators were profiled in plasma, and inguinal white and interscapular brown adipose tissues. We identified over 30 species of altered lipid mediators between diets and found that these changes were unique to each tissue. We identified changes to lipid mediators with known functional roles in the regulation of adipose tissue expansion and function, and found that there was a relationship between the average fold difference in lipid mediators between brown adipose tissue and plasma in mice consuming the SOLF diet. Our findings emphasize that even with a low-fat diet, dietary fat quality has a profound effect on lipid mediator profiles in adipose tissues and plasma.

While there is considerable evidence supporting health benefits of consuming diets high in omega-3 (n-3) fatty acids, there is no quick and effective tool to measure n-3 intake. The objective of this study was to evaluate the accuracy of a rapid assessment questionnaire (the Omega-3 Checklist) used to quantify intake of n-3 fatty acids. This was done by comparing n-3 intakes to blood biomarkers of n-3 exposure in a population of healthy men and women. In addition, a separate analysis was run including covariates age, sex, and weight, which have been shown to affect n-3 biomarker levels. Reported intake of eicosapentaenoic acid (EPA), docoshexaenoic acid (DHA), and EPA + DHA was correlated with erythrocyte EPA (Spearman's rank correlation r s = 0.51, p < 0.001), DHA (r s = 0.54, p < 0.001), and the Omega-3 Index (r s = 0.57, p < 0.001). These associations remained significant when controlling for age, sex, and weight. Therefore, the Omega-3 Checklist can be a useful, rapid assessment tool to estimate individuals' EPA and DHA intake.Lipids (2019) 54: 321-328. AbbreviationsALA α-linolenic acid DHA docoshexaenoic acid EPA eicosapentaenoic acid FFQ food frequency questionnaire n-3

Scope Higher circulating linoleic acid (LA) and muscle‐derived tetralinoleoyl‐cardiolipin (LA4CL) are each associated with decreased cardiometabolic disease risk. Mitochondrial dysfunction occurs with low LA4CL. Whether LA‐rich oil fortification can increase LA4CL in humans is unknown. The aims of this study are to determine whether dietary fortification with LA‐rich oil for 2 weeks increases: 1) LA in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC); and 2) LA4CL in PBMC in adults. Methods and results In this randomized controlled trial, adults are instructed to consume one cookie per day delivering 10 g grapeseed (LA‐cookie, N = 42) or high oleate (OA) safflower (OA‐cookie, N = 42) oil. In the LA‐cookie group, LA increases in plasma, erythrocyte, and PBMC by 6%, 7%, and 10% respectively. PBMC and erythrocyte OA increase by 7% and 4% in the OA‐cookie group but is unchanged in the plasma. PBMC LA4CL increases (5%) while LA3OA1 CL decreases (7%) in the LA‐cookie group but are unaltered in the OA‐cookie group. Conclusions LA‐rich oil fortification increases while OA‐oil has no effect on LA4CL in adults. Because LA‐rich oil fortification reduces cardiometabolic disease risk and increases LA4CL, determining whether mitochondrial dysfunction is repaired through dietary fortification is warranted.