title: Enhanced fatty acid flux triggered by adiponectin overexpression.
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.
authors: Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9052, USA.
authors: Shoba
authors: S
authors: Shetty
authors: Maria A
authors: MA
authors: Ramos-Roman
authors: You-Ree
authors: YR
authors: Cho
authors: Jonathan
authors: J
authors: Brown
authors: Jorge
authors: J
authors: Plutzky
authors: Eric S
authors: ES
authors: Muise
authors: Jay D
authors: JD
authors: Horton
authors: Philipp E
authors: PE
authors: Scherer
authors: Elizabeth J
authors: EJ
authors: Parks
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D005227:Fatty Acids; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012176:Retinoids; D014280:Triglycerides; D014801:Vitamin A