title: mTOR remains unchanged in diet-resistant (DR) rats despite impaired LKB1/AMPK cascade in adipose tissue.
abstract: Liver kinase B1 (LKB1) plays an important role in adipogenesis, but the underlying molecular mechanism is poorly understood. Here, we explored the functional relationship between LKB1 and the mammalian target of rapamycin (mTOR) in regulating adipogenesis in rats and preadipocytes. We found that LKB1 and the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) cascade are impaired in the white adipose tissue (WAT) of diet-induced obesity (DIO) and diet-resistant (DR) rats when compared with chow-fed (CF) rats. While DIO activated the mTOR pathway in WAT and led to a more fat mass gain, DR maintained the normal activity of the mTOR pathway and normal weight and percentage of fat mass. We further constructed overexpressed LKB1 (OE) and silenced LKB1 (Si) 3T3-L1 preadipocytes monoclonal cell lines. In the OE cell line, the mTOR pathway was inactivated, and intracellular lipid content was reduced during differentiation. This effect could be reversed by AMPK inhibition. Conversely, in the Si cell line, the mTOR pathway was activated and intracellular lipid content increased. This effect could be reversed by rapamycin, an inhibitor of mTOR. Our results suggest that mTOR mediates the effect of LKB1 on adipogenesis, and normal activity of mTOR in DR rats interferes with the effect of LKB1 in WAT.
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China. Electronic address: tiandr@tmu.edu.cn.
authors.forename: Derun
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Pengjiao
authors.initials: P
authors.lastname: Xi
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Haomin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy and Histology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D029968:Escherichia coli Proteins; D008297:Male; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C560213:lysis protein, E coli; C546845:mTOR protein, rat; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases
keywords: Adipogenesis; Diet-induced obesity; Diet-resistant; LKB1; Preadipocytes; mTOR