title: Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.
abstract: Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and 0.50 μg/ml) significantly reduced the metabolic activity of PTCs, and significantly decreased protein content per cell. Investigation of the role of p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that the mTOR pathway is responsible for the reduction in PTC metabolic activity in response to leptin. However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway.
authors.affiliation: Biomedical and Lifestyle Diseases (BioLED) Unit, College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia; Department of Physiology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jessica F
authors.initials: JF
authors.lastname: Briffa
authors.affiliation: Biomedical and Lifestyle Diseases (BioLED) Unit, College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia.
authors.forename: Esther
authors.initials: E
authors.lastname: Grinfeld
authors.affiliation: Biomedical and Lifestyle Diseases (BioLED) Unit, College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McAinch
authors.affiliation: School of Medical Sciences, The Bosch Institute, The University of Sydney, NSW 2006, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Poronnik
authors.affiliation: Biomedical and Lifestyle Diseases (BioLED) Unit, College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia; Department of Physiology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: Deanne.Skelly@unimelb.edu.au.
authors.forename: Deanne H
authors.initials: DH
authors.lastname: Hryciw
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009893:Opossums; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000418:Albumins; D020738:Leptin; D054411:Receptors, Leptin; D050791:STAT Transcription Factors; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005947:Glucose
keywords: Kidney; Leptin; Metabolic activity; Proximal tubule; p44/42 MAPK