RATIONALE: Adipose tissue and skeletal muscle dysfunction are hallmarks of obesity and insulin resistance. Bioactive peptides derived from food sources including milk and dairy products have gained interest for their roles in obesity and insulin resistance. However, it remains unclear whether and how whey impacts adipose and muscle metabolism and insulin function. HYPOTHESIS: Bioactive whey peptides have a positive metabolic and insulin-sensitizing effect on adipocytes and muscle cells. METHODS: Whey peptide mixture was generated via the hydrolysis of whey protein with pepsin and pancreatin. 3T3-L1 pre-adipocytes were incubated with 2.5 mg/ml bovine serum albumin (BSA) or whey peptides during differentiation. The effects on whey peptides on differentiation and insulin signaling were examined through immunoblotting and on lipid metabolism through lipidomics and lipolysis assays. Insulin resistant C2C12 myotubes were co-incubated with BSA or whey peptides for 16 h followed by insulin signaling analysis and lipidomics. RESULTS: In 3T3-L1 cells, whey peptides increased expression of the master-regulators of adipogenesis, C/EBPα and PPARγ and was associated with increased diacylglycerol (DAG) and triacylglycerol (TAG) levels. Paradoxically, expression of the lipolytic enzymes, HSL and ATGL, were also markedly increased by whey peptides, which corresponded with increased lipolytic capacity under basal and isoproterenol stimulated conditions. Insulin signaling was unchanged in insulin resistant adipocytes incubated with whey peptides. In C2C12 myotubes, whey peptides protected from palmitate-induced insulin resistance, possibly by exerting a potent anti-inflammatory effect. Furthermore, lipidomic analysis showed that whey peptides decrease levels of the lipotoxic lipid DAG and increase levels of TAGs. CONCLUSIONS: Whey peptides promote a pro-adipogenic phenotype in adipocytes, but do not alter adipocyte insulin sensitivity. In myotubes exposed to an obese-diabetic milieu, whey peptides ameliorate insulin resistance, potentially by reducing inflammation and accumulation of lipotoxic species.

Effect of whey peptides on metabolism and insulin signaling in muscle and fat cells

2019 Fall National Meeting

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