Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function

摘要

SUMMARY Brown (BAT) and white (WAT) adipose tissues play distinct roles in maintaining whole-body energy ho-meostasis, and their dysfunction can contribute to non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a cellular energy sensor, but its role in regulating BAT and WAT metabolism is unclear. We generated an inducible model for deletion of the two AMPK p subunits in adipocytes (ipip2AKO) and found that ipip2AKO mice were cold intolerant and resistant to p-adrenergic activation of BAT and beiging of WAT. BAT from ipi P2AKO mice had impairments in mitochondrial structure, function, and markers of mi-tophagy. In response to a high-fat diet, ipi P2AKO mice more rapidly developed liver steatosis as well as glucose and insulin intolerance. Thus, AMPK in adipocytes is vital for maintaining mitochondrial integrity, responding to pharmacological agents and thermal stress, and protecting against nutrient-overload-induced NAFLD and insulin resistance.