Browning-inducers modify the differentiation of human adipocytes from different anatomical sites and enhance their mitochondrial respiration

Abstract

Several studies highlighted the strong negative correlation between obesity and active brown adipose tissue amount in adult humans. There are at least two types of thermogenic fat depots, classical brown and beige, which have different origins and tissue distribution [1]. We intended to clarify whether preadipocytes from different anatomical sites are capable of initiating a browning program in parallel with the enhancement of mitochondrial respiration in response to browning-inducers. Preadipocytes obtained from herniotomy (abdominal subcutaneous) or thyroid surgery (“deep neck” and cervical subcutaneous) and a human preadipocyte cell line (SGBS) were differentiated into white, brown (by BMP7 treatment) or beige (by irisin and clozapine administration or by a previously described cocktail) adipocytes. To assess browning, gene expression measurements and laser-scanning cytometry based morphology analysis were performed [2]. Oxygen consumption was measured using an XF96 oxymeter. Differentiating adipocytes treated with browning-inducers had smaller lipid droplets, more mitochondrial DNA, higher mitochondrial respiration and contained more Ucp1 protein than white adipocytes. Browning adipocytes utilize more fatty acids by beta-oxidation and increase their respiration by activating a futile cycle of creatine metabolism [3]. Next, we intend to identify molecular markers to characterize those preadipocytes that are capable to implement an effective browning program.