Browning of human white adipocytes

Thesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.In mammals, there are two types of adipose tissue, white adipose tissue (WAT) for energy storage and brown adipose tissue for thermogenic energy expenditure. Brown adipose tissue is hypothesized to be useful in combating the obesity by burning stored fat in the body, therefore, many research groups are putting efforts to generate brown or brown-like adipocytes (also called "brite" adipocytes). Previous studies showed that adipogenic progenitors could be differentiated into brown adipocytes. Also, a recent study has shown to promote browning of mouse and human white adipocytes. In the present study, our goal was to test if differentiated cultured human primary white adipocytes could be converted to brown-like adipocytes by treatment with a PPARγ-agonist, rosiglitazone. We found that the treatment of mature human white adipocytes with 100nM and 1000nM rosiglitazone for 7 days induced the expression of brown adipocyte markers, uncoupling protein 1 (UCP1) and cell death-inducing DFFA-like effector A (CIDEA). The expression of carnitine palmitoyltransferase 1B (CPT1β). gene associated with fatty acid oxidation, was significantly increased. Also, the expression of fatty acid-binding protein 3 (FABP3) and Perilipin 5 (PLIN5), which play a role in fatty acid handling in adipocytes, was significantly increased in rosiglitazone treated human white adipocytes. Furthermore, Perin expression, measure of mitochondrial density, was increased significantly. It was accompanied by increased oxygen consumption in a preliminary study. Moreover, we observed increased lipolysis and triglyceride accumulation in rosiglitazone treated human white adipocytes. Overall, our study shows that chronic treatment of mature human adipocytes with rosiglitazone could convert them into "brite" adipocytes