title: Liver kinase b1 is required for white adipose tissue growth and differentiation.
abstract: White adipose tissue (WAT) is not only a lipogenic and fat storage tissue but also an important endocrine organ that regulates energy homeostasis, lipid metabolism, appetite, fertility, and immune and stress responses. Liver kinase B1 (LKB1), a tumor suppressor, is a key regulator in energy metabolism. However, the role of LKB1 in adipogenesis is unknown. The current study aimed to determine the contributions of LKB1 to adipogenesis in vivo. Using the Fabp4-Cre/loxP system, we generated adipose tissue-specific LKB1 knockout (LKB1(ad-/-)) mice. LKB1(ad-/-) mice exhibited a reduced amount of WAT, postnatal growth retardation, and early death before weaning. Further, LKB1 deletion markedly reduced the levels of insulin receptor substrate 1 (IRS1), peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and phosphorylated AMP-activated protein kinase (AMPK). Consistent with these results, overexpression of constitutively active AMPK partially ablated IRS1 degradation in LKB1-deficient cells. LKB1 deletion increased the levels of F-box/WD repeat-containing protein (Fbw) 8, the IRS1 ubiquitination E3 ligase. Silencing of Fbw8 increased IRS1 levels. Finally, promoter analysis and DNA chromatin immunoprecipitation analysis identified three sterol regulatory element (SRE) sites in the Fbw8 promoter, where SRE-binding protein 1c binds and induces the expression of Fbw8. Taken together, these data indicate that LKB1 controls IRS1-dependent adipogenesis via AMPK in WAT.
authors: Section of Molecule Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Wencheng
authors: W
authors: Zhang
authors: Qilong
authors: Q
authors: Wang
authors: Ping
authors: P
authors: Song
authors: Ming-Hui
authors: MH
authors: Zou
mesh_terms: D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase
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