Whey Protein Supplementation Improves the Glycemic Response and May Reduce Non-Alcoholic Fatty Liver Disease Related Biomarkers in Women with Polycystic Ovary Syndrome (PCOS).

Polycystic ovary syndrome (PCOS) increases type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) with insulin resistance. We hypothesized that a 35 g whey preload would improve insulin sensitivity and glucose handling while reducing biomarkers associated with NAFLD. Twenty-nine age-matched women (CON = 15, PCOS = 14) completed oral glycemic tolerance tests following baseline (Day 0) as well as an acute (Day 1) and short-term whey supplementation (Day 7). Whey had an interaction effect on glucose (p = 0.02) and insulin (p = 0.03), with glucose remaining stable and insulin increasing with whey supplementation. Insulin sensitivity (p < 0.01) improved with whey associated with increased glucagon secretion (p < 0.01). Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) remained unchanged, but "day" had an effect on the AST:ALT ratio (p = 0.04), whereas triglycerides and sex hormone binding globulin overall were greater in the PCOS group (p < 0.05). Total cholesterol decreased in PCOS (by 13%) and CON (by 8%) (NS). HepG2 cells treated with plasma from participants before and after whey decreased lipid accumulation in the PCOS group after whey (p < 0.05). Whey provided an insulinogenic and glycemic homeostatic effect in women with PCOS with the potential to combat NAFLD-consequences.

Whey protein preload enhances the active GLP-1 response and reduces circulating glucose in women with polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) increases risk for development of type 2 diabetes. Whey protein ingestion before a carbohydrate load attenuates blood glucose. For our exploratory, case-control study design, we hypothesized that 35 g whey protein isolate (WPI) preloading would increase postprandial incretins and reduce hyperglycemia in women with PCOS. Twenty-nine age-matched women (PCO = 14 and CON = 15) completed oral glycemic tolerance tests (OGTT) following baseline (Day 0) as well as 35 g WPI acute (Day 1) and short-term supplementation (Day 7). Eight venous samples were collected during each test for quantification of glucose, and enteropancreatic hormones and to calculate area under the curve (AUC). Data was analyzed via repeated measures ANCOVA with significance set at P< .05. "Day x time x group" significantly influenced glucose (P = .01) and insulin changes (P = .03). In both groups, AUCglu were significantly lower on Day 7 than Day 0 (P< .05). Postprandial glucose excursions were lower on Days 1 and 7 than Day 0 in PCO and CON. Both, PCO and CON exhibited greater insulin changes on Days 1 and 7 compared to Day 0 (P< .05). AUCglucagon were higher on Days 1 and 7 than on Day 0 (P< .05). Changes in active GLP-1 were higher on Day 1 than Day 0 (P= .03). Overall, we showed that WPI preloading augmented insulin release and consequently lowered circulating glucose in women with and without PCOS. This insulinogenic effect can be attributed to enhanced active GLP-1 levels. We concluded that the incretin-mimetic effect of WPI may aid women with PCOS in achieving glycemic homeostasis.

Adipose tissue inflammation in insulin resistance: review of mechanisms mediating anti-inflammatory effects of omega-3 polyunsaturated fatty acids.

Obesity is an increasingly costly and widespread epidemic, effecting 1 in 10 adults worldwide. It has been causally linked with both the metabolic syndrome and insulin resistance, both of which are associated with increased chronic inflammation. The exact mechanisms through which inflammation may contribute to both MetS and IR are numerous and their details are still largely unknown. Recently, micro-RNAs (miRNAs) have emerged as potential interventional targets due to their potential preventive roles in the pathogenesis of several diseases, including MetS and obesity. The purpose of this review paper is to discuss some of the known roles of miRNAs as mediators of inflammation-associated obesity and IR and how omega-3 polyunsaturated fatty acids may be used as a nutritional intervention for these disorders.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

OBJECTIVE: The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. METHODS: Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. RESULTS: No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. CONCLUSIONS: These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells.

Eicosapentaenoic acid reduces adipocyte hypertrophy and inflammation in diet-induced obese mice in an adiposity-independent manner.

BACKGROUND: Obesity is associated with an overexpansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation, and thrombosis. Research to develop nutritional interventions to prevent or treat obesity and its associated diseases is greatly needed. Previously, we demonstrated the ability of eicosapentaenoic acid (EPA) to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation in mice. OBJECTIVE: The objective of the current study was to determine the mechanisms mediating the anti-inflammatory and antilipogenic actions of EPA. METHODS: In a previous study, male C57BL/6J mice were fed a low-fat diet (10% of energy from fat), an HF diet (45% of energy from fat), or an HF diet supplemented with EPA (45% of energy from fat; 36 g/kg EPA; HF+EPA) for 11 wk or an HF diet for 6 wk and then switched to the HF+EPA diet for 5 wk. In this study, we used histology/immunohistochemistry, gene expression, and metabolomic analyses of white adipose tissue from these mice. In addition, cultured mouse 3T3-L1 adipocytes were treated with 100 µM EPA for 48 h and then used for extracellular flux assays with untreated 3T3-L1 adipocytes used as a control. RESULTS: Compared with the HF diet, the HF+EPA diet significantly reduced body weight, adiposity, adipocyte size, and macrophage infiltration into adipose tissue. No significant differences in overall body weight or fat pad weights were observed between HF-fed mice vs. those fed the HF+EPA diet for a short time after first inducing obesity with the HF diet. Interestingly, both histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed the HF diet and then switched to the HF+EPA diet vs. those fed HF diets only. This indicated that EPA was able to prevent as well as reverse HF-diet-induced adipocyte inflammation and hypertrophy and that some of the metabolic effects of EPA were independent of body weight or adiposity. In addition, adipose tissue metabolomic data and cultured adipocyte extracellular flux bioenergetic assays indicated that EPA also regulated mitochondrial function by increasing fatty acid oxidation and oxygen consumption, respectively. CONCLUSION: With the use of mice and cultured adipocytes, we showed that EPA ameliorates HF-diet effects at least in part by increasing oxygen consumption and fatty acid oxidation and reducing adipocyte size, adipogenesis, and adipose tissue inflammation, independent of obesity.

Nutrimetabolomics.

Metabolic pathways are tightly regulated in a tissue-specific manner to maintain whole-body homeostasis. Nutrients and hormones control these pathways at the level of transcription, translation, and/or post-translation. Genomic and proteomic tools have been predominantly used to understand metabolic regulation, and only a few studies used metabolomics approaches. Metabolomics is a powerful, unbiased approach that allows comprehensive metabolic analysis of physiologic measurements and energy balance. Thus, nutrimetabolomics can expedite our ability to identify metabolic diseases that are influenced by nutrients and to develop targeted diet-based treatments. Presentations at this symposium reviewed current resources and platforms for metabolic profiling along with statistical and bioinformatics tools for data and pathway analyses. Specific applications of metabolomics were illustrated in nutritional and disease conditions, including polycystic ovary syndrome, diabetes, and obesity and in host-gut microbiome interactions.