Enhanced fatty acid flux triggered by adiponectin overexpression

Shoba Shetty, Maria A. Ramos-Roman, You Ree Cho, Jonathan Brown, Jorge Plutzky, Eric S. Muise, Jay D. Horton, Philipp E. Scherer, Elizabeth J. Parks

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here,we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 ± 1.5 vs. 25.3 ± 6.8 mg/kg · min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor α peroxisome proliferator-activated receptor-γ coactivator 1α and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalEndocrinology
Volume153
Issue number1
DOIs
StatePublished - Jan 1 2012

ASJC Scopus subject areas

  • Endocrinology

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