Role of cidea in britening of human white adipocytes

Abstract

There are two types of adipose tissue in mammals, white adipose tissue (WAT) and brown adipose tissue (BAT). While WAT is used to store energy, BAT dissipates energy by uncoupled oxidative phosphorylation using uncoupling protein 1 (UCP1) to generate heat. It is well known that adult humans have brown adipose tissue; however, the total volume of BAT is too small to have a significant influence on energy expenditure. Recently, researchers found that with certain induction protocols, adipogenic progenitor cells could be differentiated into brown-like adipocytes called "brite" adipocytes which have higher capacity of fatty acid oxidation. Therefore, it may be possible to increase energy expenditure in obese humans and help them lose weight by increasing the volume of their BAT. Furthermore, the increased energy expenditure may help in reducing excess metabolic substrates, e.g. free fatty acids, thus reducing obesity-associated insulin resistance which typically contributes to type 2 diabetes. UCP1 and CIDEA (cell-death inducing DNA fragmentation factor 45 like effector A) are markers of brown adipose tissue. While UCP1 is a well-studied protein associated with uncoupled respiration, the role of CIDEA in brown adipocytes is only partly understood. Like UCP1, CIDEA is highly expressed in BAT but not in mouse WAT and less expressed in human WAT. In the present study, our goals were to test whether differentiated cultured human primary white adipocytes could be converted to "brite" cells by treatment with a PPARy agonist, rosiglitazone, and to evaluate the role of CIDEA in this process. We found that 100 nM rosiglitazone treatment for 7 days was sufficient to induce expression of several brown-fat specific genes, especially UCP1 and CIDEA. Knock down of CIDEA expression by siRNA interference significantly suppressed the britening of white adipocytes. Furthermore, in mouse brown adipocytes, knock down of CIDEA led to decreased expression of UCP1 protein. These results suggest that CIDEA plays an important role in fatty acid oxidation in brown adipocytes, and it might in fact be a regulatory protein in "britening" of white adipocytes.