Abstract
The triglyceride/fatty acid cycle is regulated by the phosphoenolpyruvate carboxykinase (PEPCK‐C) gene. PEPCK‐C gene is expressed primarily in the liver, kidney, adipose tissue as well as the mammary gland. The role of PEPCK‐C in the mammary gland, however, is not clearly understood. Analysis of epithelial cells from the mammary gland indicated that PEPCK‐C expression is induced by progesterone and is required for synthesis of triglyceride through the glyceroneogenesis pathway. Using a mouse model with a deletion of the PPAR binding site in the endogenous PEPCK‐C gene promoter (PPARE−/− mice), we have ablated the PEPCK‐C gene expression in the white adipose tissue (WAT), the mammary gland tissue and reduced PEPCK‐C expression in the brown adipose tissue (BAT). The PPARE−/− females are fertile and able to produce milk for their young; however, the triglyceride content of the milk from the PPARE−/− mothers contains 40% less than the wild type mice. The reduced triglyceride content in the milk has metabolic consequences. Pups from PPARE−/− mothers exhibit insulin resistance as early as 9‐days after birth and this insulin resistance persisted into adulthood. Analysis of the adult PPARE−/− mice by glucose clamps and 2‐deoxyglucose uptake have shown that the PPARE−/− mice have reduced glucose uptake and reduced AKT‐Thr308 phosphorylation. These data suggest that the glyceroneogenesis pathway in the mammary gland and adipose tissues contributes to overall development of insulin resistance.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call