| First Author | Nelson VL | Year | 2014 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 306 |
| Issue | 10 | Pages | E1205-16 |
| PubMed ID | 24691033 | Mgi Jnum | J:213164 |
| Mgi Id | MGI:5582991 | Doi | 10.1152/ajpendo.00625.2013 |
| Citation | Nelson VL, et al. (2014) Adipose tissue insulin resistance due to loss of PI3K p110alpha leads to decreased energy expenditure and obesity. Am J Physiol Endocrinol Metab 306(10):E1205-16 |
| abstractText | 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 p110alpha or p110beta specifically in the white and brown adipose tissue. The loss of p110alpha, not p110beta, resulted in increased adiposity, glucose intolerance and liver steatosis. Mice lacking p110alpha 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 p110alpha 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. |
