title: Acidosis downregulates leptin production from cultured adipocytes through a glucose transport-dependent post-transcriptional mechanism.
abstract: Metabolic acidosis, a common feature of uremia, has a well documented wasting effect on skeletal muscle. In contrast, the effect of metabolic acidosis on adipose tissue is unknown. Serum levels of the adipocyte hormone leptin have been shown to be lower in acidotic uremic rats when compared with uremic controls. This study investigated the effect of acidosis on leptin protein secretion and leptin gene expression. This was studied in vitro by means of 3T3-L1 cultured adipocytes. Leptin secretion was decreased at an acid pH of 7.1 compared with a control pH of 7.5 (1277 versus 1950 pg/well/48 h, P < 0.05). In contrast, acidosis did not affect leptin mRNA content. Glucose transport was reduced by 39% at pH 7.1 at 24 h, which was comparable in magnitude with the inhibition of leptin secretion at the same pH. The glucose transport inhibitors cytochalasin B (0.5 to 50 micro M) and phloretin (0.05 to 0.25 mM) mimicked the effect of acidosis and reduced leptin secretion in a dose-dependent fashion (P < 0.02). Dose-response curves for the inhibition of glucose uptake showed that decreasing glucose transport to the same extent as with acid was sufficient to drive down leptin secretion, independently of changes of leptin mRNA. Acid decreases leptin secretion from 3T3-L1 adipocytes through a post-transcriptional mechanism via changes in glucose transport. This starvation-like response may be physiologically important in conditions such as uremia to prevent excessive energy expenditure.
authors.affiliation: Division of Nephrology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Daniel.Teta@chuv.hospvd.ch
authors.forename: Daniel
authors.initials: D
authors.lastname: Teta
authors.forename: Alan
authors.initials: A
authors.lastname: Bevington
authors.forename: Jeremy
authors.initials: J
authors.lastname: Brown
authors.forename: Izabella
authors.initials: I
authors.lastname: Pawluczyk
authors.forename: Kevin
authors.initials: K
authors.lastname: Harris
authors.forename: John
authors.initials: J
authors.lastname: Walls
mesh_terms: D016475:3T3 Cells; D000138:Acidosis / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D015536:Down-Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D020738:Leptin / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D005947:Glucose