Calorie restriction prevents diet-induced insulin resistance independently of PGC-1-driven mitochondrial biogenesis in white adipose tissue

What is it about?

Calorie restriction (CR) exerts remarkable beneficial effects on health, preventing insulin resistance and type 2 diabetes, among other metabolic diseases. However, the mechanisms by which CR exerts is positive effects on health are not fully understood. Because white adipose tissue (WAT) is very important in the control of glucose metabolism, we aimed at identifying the main cellular processes regulated in WAT in response to CR in a pathological context of obesity. For this, a gene expression profiling study was first conducted in mice fed ad libitum with a diet rich in fat or subjected to CR. We found that the genes network to mitochondria was the most highly up-regulated in WAT by CR. To study the role that increased mitochondrial function plays on glucose metabolism following CR, we engineered a mouse model devoid specifically in adipocytes of the transcriptional co-activators PGC-1α and PGC-1β, two crucial regulators of mitochondrial biogenesis. Our results show that mice lacking PGC-1s in adipocytes are unable to increase mitochondrial biogenesis in WAT in response to CR. Despite a blunted induction of mitochondrial biogenesis in response to calorie deprivation, mice lacking adipose PGC-1s still retain the capacity of improving glucose homeostasis. Our study demonstrates that PGC-1 co-activators are major regulators of CR-induced mitochondrial biogenesis in WAT and that increased mitochondrial biogenesis and oxidative function in adipose tissue are not required for the improvement of glucose metabolism control mediated by CR.

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