title: Up-regulation of hepatic lipolysis stimulated lipoprotein receptor by leptin: a potential lever for controlling lipid clearance during the postprandial phase.
abstract: As a hepatic receptor for triglyceride-rich lipoproteins, the lipolysis-stimulated lipoprotein receptor (LSR) may be involved in the dynamics of lipid distribution between the liver and peripheral tissues. Here, we explore the potential role of leptin in regulating LSR. At physiological concentrations (1-10 ng/ml), leptin increased LSR protein and mRNA levels in Hepa1-6 cells through an ERK1/2-dependent and α-amanitin-sensitive pathway. In vivo, leptin treatment of C57BL6/Rj mice (1 μg 2×/d, 8 d) led to a significant increase in hepatic LSR mRNA and protein, decreased liver triglycerides and increased VLDL secretion as compared to controls. LSR(+/-) mice with elevated postprandial lipemia placed on a high-fat (60% kcal) diet exhibited accelerated weight gain and increased fat mass as compared to controls. While plasma leptin levels were increased 3-fold, hepatic leptin receptor protein levels and phosphorylation of ERK1/2 were significantly reduced. Therefore, leptin is an important regulator of LSR protein levels providing the means for the control of hepatic uptake of lipids during the postprandial phase. However, this may no longer be functional in LSR(+/-) mice placed under a chronic dietary fat load, suggesting that this animal model could be useful for the study of molecular mechanisms involved in peripheral leptin resistance.
authors.affiliation: Lipidomix, Nancy University, Institut National Polytechnique de Lorraine-Ecole Nationale Supérieure d'Agronomie et des Industries Alimentaires (INPL ENSAIA), Vandoeuvre-lès-Nancy, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Stenger
authors.forename: Marine
authors.initials: M
authors.lastname: Hanse
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pratte
authors.forename: Marie-Ludvine
authors.initials: ML
authors.lastname: Mbala
authors.forename: Samina
authors.initials: S
authors.lastname: Akbar
authors.forename: Violette
authors.initials: V
authors.lastname: Koziel
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Escanyé
authors.forename: Badreddine
authors.initials: B
authors.lastname: Kriem
authors.forename: Catherine
authors.initials: C
authors.lastname: Malaplate-Armand
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Olivier
authors.forename: Thierry
authors.initials: T
authors.lastname: Oster
authors.forename: Thierry
authors.initials: T
authors.lastname: Pillot
authors.forename: Frances T
authors.initials: FT
authors.lastname: Yen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D019518:Postprandial Period; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D020738:Leptin; D018110:Receptors, Lipoprotein