An Egg White-Derived Peptide Enhances Systemic Insulin Sensitivity and Modulates Markers of Non-Alcoholic Fatty Liver Disease in Obese, Insulin Resistant Mice.

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a global health problem. Currently, no pharmacological treatment is approved for NAFLD. Natural health products, including bioactive peptides, are potential candidates to aid in the management of metabolic syndrome-related conditions, including insulin resistance and obesity. In this study, we hypothesized that an egg-white-derived bioactive peptide QAMPFRVTEQE (Peptide 2) would improve systemic and local white adipose tissue insulin sensitivity, thereby preventing high-fat diet-induced exacerbation of pathological features associated with NAFLD, such as lipid droplet size and number, inflammation, and hepatocyte hypertrophy in high-fat diet-fed mice. Similar to rosiglitazone, Peptide 2 supplementation improved systemic insulin resistance during the hyperinsulinemic-euglycemic clamp and enhanced insulin signalling in white adipose tissue, modulating ex vivo lipolysis. In the liver, compared with high-fat diet fed animals, Peptide 2 supplemented animals presented decreased hepatic cholesterol accumulation (p < 0.05) and area of individual hepatic lipid droplet by around 50% (p = 0.09) and reduced hepatic inflammatory infiltration (p < 0.05) whereas rosiglitazone exacerbated steatosis. In conclusion, Peptide 2 supplementation improved insulin sensitivity and decreased hepatic steatosis, unlike the insulin-sensitizing drug rosiglitazone.

Elevated miR-143 and miR-34a gene expression in human visceral adipose tissue are associated with insulin resistance in non-diabetic adults: a cross-sectional study.

OBJECTIVE: We aimed to evaluate the association of miR-143 and miR-34a expression in human visceral (VAT) and subcutaneous (SAT) adipose tissues with insulin resistance (IR). METHODS: VAT and SAT were obtained from 176 participants without diabetes. miR-143 and miR-34a expressions in VAT and SAT were measured using qRT-PCR. Fasting serum insulin and glucose concentration, homeostatic model assessment of IR index (HOMA-IR) and ß-cell function (HOMA-B), and quantitative insulin-sensitivity check index (QUICKI) were calculated. RESULTS: After adjustment for age, sex and body mass index (BMI), VAT miR-143 expression was positively associated with fasting plasma glucose (FPG), insulin, and HOMA-IR, and negatively associated with HOMA-B and QUICKI. miR-34a expression in VAT was directly associated with FPG, insulin, and HOMA-IR and negatively associated with QUICKI. In SAT, miR-34a expression was positively associated with insulin and negatively associated with QUICKI. The interaction terms of HOMA-IR and BMI categories were significant for both miR gene expressions in VAT. After stratifying participants based on BMI, the association of miR-143 and miR-34a expressions in VAT with IR indices remained significant only in obese patients. CONCLUSION: miR-143 and miR-34a expressions in VAT were independent predictors of IR in people without diabetes, and that this association was conditional on the degree of obesity. LEVEL OF EVIDENCE: Level of evidence III, cross-sectional analytic study.

IRW (Isoleucine-Arginine-Tryptophan) Improves Glucose Tolerance in High Fat Diet Fed C57BL/6 Mice via Activation of Insulin Signaling and AMPK Pathways in Skeletal Muscle.

IRW (Isoleucine−Arginine−Tryptophan), has antihypertensive and anti-inflammatory properties in cells and animal models and prevents angiotensin-II- and tumor necrosis factor (TNF)-α-induced insulin resistance (IR) in vitro. We investigated the effects of IRW on body composition, glucose homeostasis and insulin sensitivity in a high-fat diet (HFD) induced insulin resistant (IR) model. C57BL/6 mice were fed HFD for 6 weeks, after which IRW was incorporated into the diet (45 or 15 mg/kg body weight (BW)) until week 14. IRW45 (at a dose of 45 mg/kg BW) reduced BW (p = 0.0327), fat mass gain (p = 0.0085), and preserved lean mass of HFD mice (p = 0.0065), concomitant with enhanced glucose tolerance and reduced fasting glucose (p < 0.001). In skeletal muscle, IRW45 increased insulin-stimulated protein kinase B (AKT) phosphorylation (p = 0.0132) and glucose transporter 4 (GLUT4) translocation (p < 0.001). Angiotensin 2 receptor (AT2R) (p = 0.0024), phosphorylated 5'-AMP-activated protein kinase (AMPKα) (p < 0.0124) and peroxisome proliferator-activated receptor gamma (PPARγ) (p < 0.001) were enhanced in skeletal muscle of IRW45-treated mice, as was the expression of genes involved in myogenesis. Plasma angiotensin converting enzyme-2 (ACE2) activity was increased (p = 0.0016). Uncoupling protein-1 in white adipose tissue (WAT) was partially restored after IRW supplementation. IRW improves glucose tolerance and body composition in HFD-fed mice and promotes glucose uptake in skeletal muscle via multiple signaling pathways, independent of angiotensin converting enzyme (ACE) inhibition.

Bioactive Peptides: From Basic Research to Clinical Trials and Commercialization.

Chronic diseases, including metabolic diseases, have become a worldwide public health issue. Research regarding the use of bioactive peptides or protein hydrolysates derived from food, as the diet-based strategies for the prevention and mitigation of chronic diseases, has increased exponentially in the past decades. Numerous in vitro and in vivo studies report the efficacy and safety of food-derived bioactive peptides and protein hydrolysates as antihypertensive, anti-inflammatory, antidiabetic, and antioxidant agents. However, despite promising preclinical results, an inadequate understanding of their mechanisms of action and pharmacokinetics restrict their clinical translation. Commercialization of bioactive peptides can be further hindered due to scarce information regarding their efficacy, safety, bitter taste, as well as the lack of a cost-effective method of production. This review provides an overview of the current clinical evidence and challenges to commercial applications of food-derived bioactive peptides and protein hydrolysates for the prevention and alleviation of chronic diseases.

Egg and Soy-Derived Peptides and Hydrolysates: A Review of Their Physiological Actions against Diabetes and Obesity.

Type 2 diabetes and obesity are two chronic conditions associated with the metabolic syndrome and their prevalences are increasing worldwide. The investigation of food protein-derived bioactive peptides that can improve the pathophysiology of diabetes or obesity while causing minimal side effects is desired. Egg and soy proteins generate bioactive peptides with multiple biological effects, exerting nutritional and physiological benefits. This review focuses on the anti-diabetic and anti-obesity effects of egg- and soy-derived peptides and hydrolysates in vivo and in vitro relevant to these conditions. Studies using the intact protein were considered only when comparing the results with the hydrolysate or peptides. In vivo evidence suggests that bioactive peptides from egg and soy can potentially be used to manage elements of glucose homeostasis in metabolic syndrome; however, the mechanisms of action on glucose and insulin metabolism, and the interaction between peptides and their molecular targets remain unclear. Optimizing the production of egg- and soy-derived peptides and standardizing the physiological models to study their effects on diabetes and obesity could help to clarify the effects of these bioactive peptides in metabolic syndrome-related conditions.