AMP-Activated Protein Kinase α1 Protects Against Diet-Induced Insulin Resistance and Obesity Academic Article uri icon

abstract

  • AMP-activated protein kinase (AMPK) is an essential sensor of cellular energy status. Defects in the 2 catalytic subunit of AMPK (AMPK1) are associated with metabolic syndrome. The current study investigated the role AMPK1 in the pathogenesis of obesity and inflammation using male AMPK1-deficent (AMPK1(-/-)) mice and their wild-type (WT) littermates. After being fed a high-fat diet (HFD), global AMPK1(-/-) mice gained more body weight and greater adiposity and exhibited systemic insulin resistance and metabolic dysfunction with increased severity in their adipose tissues compared with their WT littermates. Interestingly, upon HFD feeding, irradiated WT mice that received the bone marrow of AMPK1(-/-) mice showed increased insulin resistance but not obesity, whereas irradiated AMPK1(-/-) mice with WT bone marrow had a phenotype of metabolic dysregulation that was similar to that of global AMPK1(-/-) mice. AMPK1 deficiency in macrophages markedly increased the macrophage proinflammatory status. In addition, AMPK1 knockdown enhanced adipocyte lipid accumulation and exacerbated the inflammatory response and insulin resistance. Together, these data show that AMPK1 protects mice from diet-induced obesity and insulin resistance, demonstrating that AMPK1 is a promising therapeutic target in the treatment of the metabolic syndrome.

published proceedings

  • Diabetes

altmetric score

  • 1.5

author list (cited authors)

  • Zhang, W., Zhang, X., Wang, H., Guo, X., Li, H., Wang, Y., ... Huo, Y.

citation count

  • 37

complete list of authors

  • Zhang, Weiyu||Zhang, Xianling||Wang, Huan||Guo, Xin||Li, Honggui||Wang, Ying||Xu, Xin||Tan, Lyhun||Mashek, Mara T||Zhang, Chunxiang||Chen, Yingjie||Mashek, Douglas G||Foretz, Marc||Zhu, Chuhong||Zhou, Huaijun||Liu, Xu||Viollet, Benoit||Wu, Chaodong||Huo, Yuqing

publication date

  • December 2012