Protein Source Determines the Effectiveness of High-Protein Diets in Improving Adipose Tissue Function and Insulin Resistance in fa/fa Zucker Rats.

BACKGROUND/OBJECTIVES: Obesity and insulin resistance are increasing globally. Emerging evidence suggests that not only the quantity but also the source of dietary protein may improve metabolic health outcomes. This study evaluated the effects of high-protein diets (HPDs) containing animal or plant protein sources on obesity and obesity-related metabolic markers in a rodent model of genetic obesity. METHODS: Obese male fa/fa Zucker rats were fed HPDs (35% of energy) containing protein from different sources (casein, egg white protein, soy + pea protein, mixture of egg white + soy + pea proteins) or a normal protein diet (15% of energy) containing casein over 8 weeks. Oral glucose tolerance, weight gain, fat depots, serum biochemistry, adipocyte and pancreatic islet size, and markers of adipose tissue lipolysis, insulin signaling, and immune cells were assessed. RESULTS: Consumption of HPDs containing egg white protein, soy + pea, or their mixture resulted in smaller adipocytes compared to the casein diets, despite greater weight gain, elevated serum NEFA, and more total visceral fat in the HPD plant group. These HPD groups had reduced fasting insulin and no compensatory pancreatic islet enlargement. CD3 levels were elevated in adipose tissue without changes in F4/80, and no differences were observed in ATGL, HSL, Akt or AS160. CONCLUSIONS: The source of dietary protein in HPDs significantly influences metabolic outcomes in obese rats, impacting adipocyte and pancreatic islet size, insulinemia, and immune cell markers in adipose tissue. These findings support the potential of employing targeted dietary protein interventions for managing obesity-related metabolic disorders.