title: AMP-activated protein kinase α1 protects against diet-induced insulin resistance and obesity.
abstract: AMP-activated protein kinase (AMPK) is an essential sensor of cellular energy status. Defects in the α2 catalytic subunit of AMPK (AMPKα1) are associated with metabolic syndrome. The current study investigated the role AMPKα1 in the pathogenesis of obesity and inflammation using male AMPKα1-deficent (AMPKα1(-/-)) mice and their wild-type (WT) littermates. After being fed a high-fat diet (HFD), global AMPKα1(-/-) 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 AMPKα1(-/-) mice showed increased insulin resistance but not obesity, whereas irradiated AMPKα1(-/-) mice with WT bone marrow had a phenotype of metabolic dysregulation that was similar to that of global AMPKα1(-/-) mice. AMPKα1 deficiency in macrophages markedly increased the macrophage proinflammatory status. In addition, AMPKα1 knockdown enhanced adipocyte lipid accumulation and exacerbated the inflammatory response and insulin resistance. Together, these data show that AMPKα1 protects mice from diet-induced obesity and insulin resistance, demonstrating that AMPKα1 is a promising therapeutic target in the treatment of the metabolic syndrome.
authors: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Weiyu
authors: W
authors: Zhang
authors: Xianling
authors: X
authors: Zhang
authors: Huan
authors: H
authors: Wang
authors: Xin
authors: X
authors: Guo
authors: Honggui
authors: H
authors: Li
authors: Ying
authors: Y
authors: Wang
authors: Xin
authors: X
authors: Xu
authors: Lyhun
authors: L
authors: Tan
authors: Mara T
authors: MT
authors: Mashek
authors: Chunxiang
authors: C
authors: Zhang
authors: Yingjie
authors: Y
authors: Chen
authors: Douglas G
authors: DG
authors: Mashek
authors: Marc
authors: M
authors: Foretz
authors: Chuhong
authors: C
authors: Zhu
authors: Huaijun
authors: H
authors: Zhou
authors: Xu
authors: X
authors: Liu
authors: Benoit
authors: B
authors: Viollet
authors: Chaodong
authors: C
authors: Wu
authors: Yuqing
authors: Y
authors: Huo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D055372:AMP-Activated Protein Kinases