title: Adipose tissue insulin resistance due to loss of PI3K p110α leads to decreased energy expenditure and obesity.
abstract: Adipose tissue is a highly insulin-responsive organ that contributes to metabolic regulation. Insulin resistance in the adipose tissue affects systemic lipid and glucose homeostasis. Phosphoinositide 3-kinase (PI3K) mediates downstream insulin signaling in adipose tissue, but its physiological role in vivo remains unclear. Using Cre recombinase driven by the aP2 promoter, we created mice that lack the class 1A PI3K catalytic subunit p110α or p110β specifically in the white and brown adipose tissue. The loss of p110α, not p110β, resulted in increased adiposity, glucose intolerance and liver steatosis. Mice lacking p110α in adipose tissue exhibited a decrease in energy expenditure but no change in food intake or activity compared with control animals. This low energy expenditure is a consequence of low cellular respiration in the brown adipocytes caused by a decrease in expression of key mitochondrial genes including uncoupling protein-1. These results illustrate a critical role of p110α in the regulation of energy expenditure through modulation of cellular respiration in the brown adipose tissue and suggest that compromised insulin signaling in adipose tissue might be involved in the onset of obesity.
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York;
authors.forename: Victoria L B
authors.initials: VL
authors.lastname: Nelson
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York;
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Jiang
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York; Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Dickman
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ballou
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York; Department of Veterans Affairs Medical Center, Northport, New York richard.lin@stonybrook.edu.
authors.forename: Richard Z
authors.initials: RZ
authors.lastname: Lin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D019069:Cell Respiration / Q000235:genetics; D002478:Cells, Cultured; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology* / Q000235:genetics
chemical_list: C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases
keywords: brown adipose tissue; energy expenditure; insulin; obesity; phosphoinositide 3-kinase