title: Diet-induced obese rats exhibit impaired LKB1-AMPK signaling in hypothalamus and adipose tissue.
abstract: AMPK not only acts as a sensor of cellular energy status but also plays a critical role in the energy balance of the body. In this study, LKB1-AMPK signaling was investigated in diet-induced obese (DIO) and diet resistant (DR) rats. In hypothalamus, DIO rats had lower level of LKB1, AMPKα and pAMPKα than chow-fed or DR rats. Both orexigenic peptide NPY and anorexigenic peptide POMC expression were reduced in hypothalamus of DIO rats. i.c.v. injection of AICAR, an activator of AMPK, increased NPY expression but did not alter POMC expression in DIO rats. In periphery, LKB1 protein content and pAMPKα level were lower in the adipose tissue of DIO rats compared to chow-fed and DR rats. Moreover, pAMPKα and LKB1 protein levels obtained from epididymal fat pad were inversely correlated with epididymal fat mass. LKB1 protein content and pAMPKα in skeletal muscle of DIO rats were not different from those in the muscles of chow-fed and DR rats. In summary, DIO rats, but not DR rats, have impaired LKB1-AMPK signaling in hypothalamus and adipose tissue, suggesting the disturbed energy balance observed in DIO rats is related with abnormalities of AMPK signaling in a tissue specific manner.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing 100083, PR China.
authors.lastname: Fei-Wang
authors.forename: De-Run
authors.initials: DR
authors.lastname: Tian
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Han
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D050218:Body Fat Distribution; D048429:Cell Size; D059305:Diet, High-Fat / Q000009:adverse effects; D004822:Epididymis / Q000378:metabolism; D015870:Gene Expression; D007031:Hypothalamus / Q000201:enzymology* / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000201:enzymology* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase