Details

Autor(en) / Beteiligte

• Boughton Nelson, Victoria L

Titel

Phosphoinositide 3-Kinase (PI3K) p110α Catalytic Subunit in Adipose Tissue Regulates Systemic Metabolism

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2014

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• 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 p11α, 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 as compared to 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. We also found that increased bodyweight in male mice lacking adipose-p110α is preceded by a delay in puberty onset and corresponds with elevated leptin gene expression in the white adipose tissue suggesting that changes occurring before obesity onset contribute to metabolic impairments with age. These results illustrate a critical role of adipose-p110α in the regulation of early juvenile development and adult 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.