title: Lkb1 deletion promotes ectopic lipid accumulation in muscle progenitor cells and mature muscles.
abstract: Excessive intramyocellular triglycerides (muscle lipids) are associated with reduced contractile function, insulin resistance, and Type 2 diabetes, but what governs lipid accumulation in muscle is unclear. Here we report a role of Lkb1 in regulating lipid metabolism in muscle stem cells and their descendent mature muscles. We used Myod(Cre) and Lkb1(flox/flox) mice to specifically delete Lkb1 in myogenic cells including stem and differentiated cells, and examined the lipid accumulation and gene expression of myoblasts cultured from muscle stem cells (satellite cells). Genetic deletion of Lkb1 in myogenic progenitors led to elevated expression of lipogenic genes and ectopic lipid accumulation in proliferating myoblasts. Interestingly, the Lkb1-deficient myoblasts differentiated into adipocyte-like cells upon adipogenic induction. However, these adipocyte-like cells maintained myogenic gene expression with reduced ability to form myotubes efficiently. Activation of AMPK by AICAR prevented ectopic lipid formation in the Lkb1-null myoblasts. Notably, Lkb1-deficient muscles accumulated excessive lipids in vivo in response to high-fat diet feeding. These results demonstrate that Lkb1 acts through AMPK to limit lipid deposition in muscle stem cells and their derivative mature muscles, and point to the possibility of controlling muscle lipid content using AMPK activating drugs.
authors.affiliation: Department of Animal Science, Purdue University, West Lafayette, Indiana.
authors.forename: Tizhong
authors.initials: T
authors.lastname: Shan
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Zhang
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Bi
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005247:Feeding Behavior; D017353:Gene Deletion; D005786:Gene Expression Regulation; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000254:growth & development*; D032446:Myoblasts / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase