Bovine α-lactalbumin hydrolysates (α-LAH) ameliorate adipose insulin resistance and inflammation in high-fat diet-fed C57BL/6J mice

Abstract

Obesity-induced adipose inflammation has been demonstrated to be a key cause of insulin resistance. Peptides derived from bovine α-lactalbumin have been shown to inhibit the activities of dipeptidyl peptidase IV (DPP-IV) and angiotensin converting enzyme (ACE), scavenge 2,2′ -azinobis [3-ethylbenzothiazoline-6-sulfonate] (ABTS+) radical and stimulate glucagon-like peptide-2 secretion. In the present study, the effects of bovine α-lactalbumin hydrolysates (α-LAH) on adipose insulin resistance and inflammation induced by high-fat diet (HFD) were investigated. The insulin resistance model was established by feeding C57BL/6J mice with HFD (60% kcal from fat) for eight weeks. Then, the mice were fed with HFD and bovine α-LAH of different doses (100 mg/kg b.w., 200 mg/kg b.w. and 400 mg/kg b.w.) for another 12 weeks to evaluate its protective effects against HFD-induced insulin resistance. The oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (ipITT) were conducted after intervention with α-LAH for 10 weeks and 11 weeks, respectively. Results showed that bovine α-LAH significantly reduced body weight, blood glucose, serum insulin, and HOMA-IR (homeostatic model assessment of insulin resistance) levels, lowered the area-under-the-curve (AUC) during OGTT and ipITT, and downregulated inflammation-related gene [tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1] expression in adipose tissues of HFD-fed C57BL/6J mice. Furthermore, bovine α-LAH also suppressed insulin receptor substrate 1 (IRS-1) serine phosphorylation (Ser307, Ser612), enhanced protein kinase B (known as Akt) phosphorylation, and inhibited the activation of inhibitor of kappaB kinase (IKK) and mitogen activated protein kinase (MAPK) signaling pathways in adipose tissues of HFD-fed C57BL/6J mice. These results suggested that bovine α-LAH could ameliorate adipose insulin resistance and inflammation through IKK and MAPK signaling pathways in HFD-fed C57BL/6J mice.