title: Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet.
abstract: Accumulation of visceral fat, more so than subcutaneous fat, is strongly associated with severe metabolic complications. However, the factors regulating depot-specific adipogenesis are poorly understood. In this study, we show differential expression of pregnancy-associated plasma protein-A (PAPP-A), a secreted regulator of local insulin-like growth factor (IGF) action, in adipose tissue of mice. PAPP-A mRNA expression was fivefold higher in visceral (mesenteric) fat compared with subcutaneous (inguinal, subscapular), perirenal, and brown fat of mice. To investigate the possible role of depot-specific PAPP-A expression in fat accumulation, wild-type (WT) and PAPP-A knockout (KO) mice were fed a high-fat diet (HFD) for up to 20 wk. Adipocyte size increased in subcutaneous and perirenal depots similarly in WT and PAPP-A KO mice. However, fat cell size and in vivo lipid uptake were significantly reduced in mesenteric fat of PAPP-A KO compared with WT mice. After 20 wk on HFD, phosphorylation of AKT, a downstream signaling intermediate of IGF-I and insulin receptor activation, was significantly decreased by 50% in mesenteric compared with subcutaneous fat in WT mice, but was significantly increased threefold in mesenteric compared with subcutaneous fat in PAPP-A KO mice. This appeared to be because of enhanced insulin-stimulated signaling in mesenteric fat of PAPP-A KO mice. These data establish fat depot-specific expression of PAPP-A and indicate preferential impact of PAPP-A deficiency on visceral fat in the mouse that is associated with enhanced insulin receptor signaling. Thus, PAPP-A may be a potential target for treatment and/or prevention strategies for visceral obesity and related morbidities.
authors.affiliation: Division of Endocrinology, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
authors.forename: Sara L
authors.initials: SL
authors.lastname: Harstad
authors.forename: Tamar
authors.initials: T
authors.lastname: Tchkonia
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
mesh_terms: D017667:Adipocytes / Q000648:ultrastructure; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D048429:Cell Size; D059305:Diet, High-Fat; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000502:physiology; D050152:Intra-Abdominal Fat / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000517:prevention & control; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000172:deficiency* / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012313:RNA; C514948:PAPPA2 protein, mouse; D011266:Pregnancy-Associated Plasma Protein-A
keywords: adipose tissue; mesenteric fat
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