Globular Adiponectin Protected ob/ob Mice from Diabetes and ApoE-deficient Mice from Atherosclerosis

TLDR

Adiponectin is an adipocyte‑derived hormone that regulates energy homeostasis and insulin sensitivity. The study aimed to evaluate the effects of globular domain adiponectin (gAd) transgenic expression in leptin‑deficient ob/ob and apoE‑deficient mice. The authors generated gAd transgenic mice crossed with ob/ob or apoE‑deficient mice to assess metabolic and atherosclerotic outcomes. Globular adiponectin transgenic expression improved insulin sensitivity, preserved β‑cell function, and reduced diabetes in ob/ob mice, while also attenuating atherosclerosis in apoE‑deficient mice through upregulation of fatty‑acid oxidation pathways and downregulation of scavenger receptor and TNF‑α, demonstrating its therapeutic potential for type 2 diabetes and atherosclerosis.

Abstract

The adipocyte-derived hormone adiponectin has been shown to play important roles in the regulation of energy homeostasis and insulin sensitivity. In this study, we analyzed globular domain adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of insulin resistance and β-cell degranulation as well as diabetes, indicating that globular adiponectin and leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor α. This is the first demonstration that globular adiponectin can protect against atherosclerosis <i>in vivo</i>. In conclusion, replenishment of globular adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.