Abstract
Deregulation of lipid metabolism and insulin function in muscle and adipose tissue are hallmarks of systemic insulin resistance, which can progress to type 2 diabetes. While previous studies suggested that milk proteins influence systemic glucose homeostasis and insulin function, it remains unclear whether bioactive peptides generated from whey alter lipid metabolism and its accumulation in muscle and adipose tissue. Therefore, we incubated murine 3T3-L1 preadipocytes and C2C12 myotubes with a whey peptide mixture produced through pepsin-pancreatin digestion, mimicking peptides generated in the gut from whey protein hydrolysis, and examined its effect on indicators of lipid metabolism and insulin sensitivity. Whey peptides, particularly those derived from bovine serum albumin (BSA), promoted 3T3-L1 adipocyte differentiation and triacylglycerol (TG) accumulation in accordance with peroxisome proliferator-activated receptor γ (PPARγ) upregulation. Whey/BSA peptides also increased lipolysis and mitochondrial fat oxidation in adipocytes, which was associated with the upregulation of peroxisome proliferator-activated receptor δ (PPARδ). In C2C12 myotubes, whey but not BSA peptides ameliorated palmitate-induced insulin resistance, which was associated with reduced inflammation and diacylglycerol accumulation, and increased sequestration of fatty acids in the TG pool. Taken together, our study suggests that whey peptides generated via pepsin-pancreatin digestion profoundly alter lipid metabolism and accumulation in adipocytes and skeletal myotubes.
Highlights
Increased consumption of calorically dense foods coupled with a sedentary lifestyle can lead to obesity, a chronic metabolic disorder characterized by the accumulation of excessive adipose tissue.Obesity is associated with many comorbidities, including cancer, cardiovascular disease, and insulin resistance, which can progress to type 2 diabetes
Our study shows that whey peptides, those derived from the bovine serum albumin (BSA) component of whey, promoted 3T3-L1 adipocyte differentiation and lipid accumulation
Insulin resistance in adipose tissue and skeletal muscle drives the development of systemic insulin resistance, which can progress to type 2 diabetes [41]
Summary
Increased consumption of calorically dense foods coupled with a sedentary lifestyle can lead to obesity, a chronic metabolic disorder characterized by the accumulation of excessive adipose tissue.Obesity is associated with many comorbidities, including cancer, cardiovascular disease, and insulin resistance, which can progress to type 2 diabetes. Nutrients 2020, 12, 425 development of insulin resistance in key insulin target tissues, such as skeletal muscle and white adipose tissue (WAT) [1]. Insulin promotes TG synthesis and suppresses enzymes involved in TG hydrolysis, thereby lowering fatty acid release from adipocytes; these functions are impaired in insulin-resistant adipose tissue [4]. The inability of WAT to effectively expand in the presence of excess nutrients promotes ectopic lipid accumulation in tissues such as skeletal muscle [5]. The mechanisms implicated in insulin resistance in skeletal muscle and WAT are multifactorial and involve increased inflammation [9,10], oxidative stress [11], fibrosis [12], endoplasmic reticulum (ER) stress [13], and accumulation of toxic signaling lipids, including diacylglycerols (DGs) and ceramides [14,15]
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