Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation

TLDR

Adiponectin is implicated in energy homeostasis, insulin sensitivity, and possesses putative anti‑atherogenic properties in vitro. The study aimed to determine whether adiponectin protects against diabetes and atherosclerosis in vivo. This was achieved by generating adiponectin‑deficient mice. Adiponectin‑deficient mice exhibited progressive insulin resistance and glucose intolerance, with homozygotes showing moderate impairment, and displayed a two‑fold increase in neointimal formation after vascular injury, confirming adiponectin’s protective role against insulin resistance and atherosclerosis.

Abstract

The adipocyte-derived hormone adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity, and it has been reported to exhibit putative antiatherogenic properties <i>in vitro</i>. In this study we generated adiponectin-deficient mice to directly investigate whether adiponectin has a physiological protective role against diabetes and atherosclerosis <i>in vivo</i>. Heterozygous adiponectin-deficient (<i>adipo</i> ^+/−) mice showed mild insulin resistance, while homozygous adiponectin-deficient (<i>adipo</i> ^−/−) mice showed moderate insulin resistance with glucose intolerance despite body weight gain similar to that of wild-type mice. Moreover, <i>adipo</i> ^−/−mice showed 2-fold more neointimal formation in response to external vascular cuff injury than wild-type mice (<i>p</i> = 0.01). This study provides the first direct evidence that adiponectin plays a protective role against insulin resistance and atherosclerosis <i>in vivo</i>.