The impact of fasting on adipose tissue metabolism

Fasting and starvation were common occurrences during human evolution and accordingly have been an important environmental factor shaping human energy metabolism. Humans can tolerate fasting reasonably well through adaptative and well-orchestrated time-dependent changes in energy metabolism. Key features of the adaptive response to fasting are the breakdown of liver glycogen and muscle protein to produce glucose for the brain, as well as the gradual depletion of the fat stores, resulting in the release of glycerol and fatty acids into the bloodstream and the production of ketone bodies in the liver. In this paper, an overview is presented of our current understanding of the effects of fasting on adipose tissue metabolism. Fasting leads to reduced uptake of circulating triacylglycerols by adipocytes through inhibition of the activity of the rate-limiting enzyme lipoprotein lipase. In addition, fasting stimulates the degradation of stored triacylglycerols by activating the key enzyme adipose triglyceride lipase. The mechanisms underlying these events are discussed, with a special interest in insights gained from studies on humans. Furthermore, an overview is presented of the effects of fasting on other metabolic pathways in the adipose tissue, including fatty acid synthesis, glucose uptake, glyceroneogenesis, autophagy, and the endocrine function of adipose tissue. •Fasting activates intracellular lipolysis via multiple pathways converging on ATGL•Fasting inhibits extracellular lipolysis via induction of the LPL inhibitor ANGPTL4•Reduced insulin signaling likely is the primary driver of the metabolic changes in adipose tissue during fasting•Differences exist in the regulation of adipose tissue metabolism during fasting between mice and humans