Energy balancing by fat Pik3ca.

Obesity is often associated with systemic insulin resistance, and the decline of insulin sensitivity marks the progression of obesity into a disease state. We recently generated a mouse with adipose-specific ablation of the p110α phosphoinositide 3-kinase (PI3K) catalytic subunit to model insulin resistance in this organ. The phenotypes of this animal revealed novel roles of adipose PI3K signaling in regulating body weight and systemic glucose and lipid homeostasis. Loss of p110α in the brown adipose tissue resulted in reduced expression of mitochondrial-associated genes and decreased respiration in brown adipocytes. Reduced activity of the brown adipose tissue in p110α-null mice lowered their energy expenditure, which promoted obesity and systemic metabolic dysfunction with increased lipid deposition in the liver. Loss of PI3K activity did not affect adiposity until sexual maturation, suggesting that the effect of adipose PI3K on obesity might be linked to the development of puberty. Elevated leptin in the p110α knockout mice might interfere with the reproductive axis to delay pubertal development. The increase in adiposity induced by adipose-specific loss of p110α provides a link between insulin resistance and obesity onset and may also provide deeper insight into changes in prepubescent insulin sensitivity that can affect metabolism later in life.