Sodium butyrate modulates adipocyte expansion, adipogenesis, and insulin receptor signaling by upregulation of PPAR-γ in obese Apo E knockout mice.

Abstract

Studies suggest that sodium butyrate reduces obesity-associated inflammation and insulin resistance in in vitro and in vivo models. Apo E-/- mice have high basal oxidative stress and naturally develop dyslipidemia and atherosclerosis. Because these disorders are present in obesity, the aim of this study was to determine whether Apo E-/- mice could be a more realistic model for studying obesity and insulin resistance. We evaluated the action of orally administered sodium butyrate on adipose tissue expansion and insulin resistance using diet-induced obese Apo E-/- mice. Findings from the present study demonstrated that obese mice fed a sodium butyrate-supplemented diet presented a modest reduction of weight gain associated with reduction of adipocyte expansion, induction of adipogenesis and angiogenesis, and adiponectin production. Sodium butyrate also improved insulin sensitivity, by increasing insulin receptor expression associated with activation of Akt signaling pathway. These results were associated with increased peroxisome proliferator-activated receptor-γ expression and nuclear factor-κB downregulation. These results suggested that oral supplementation of butyrate could be useful as an adjuvant in the treatment of obesity, metabolic syndrome, and insulin resistance.