The colorful versatility of adipocytes: white‐to‐brown transdifferentiation and its therapeutic potential in humans

Abstract

Brown and brite adipocytes contribute to energy expenditure through nonshivering thermogenesis. Though these cell types are thought to arise primarily from the de novo differentiation of precursor cells, their abundance is also controlled through the transdifferentiation of mature white adipocytes. Here, we review recent advances in our understanding of the regulation of white-tobrown transdifferentiation, as well as the conversion of brown and brite adipocytes to dormant, white-like fat cells. Converting mature white adipocytes into brite cells or reactivating dormant brown and brite adipocytes has emerged as a strategy to ameliorate human metabolic disorders. We analyze the evidence of learning from mice and how they translate to humans to ultimately scrutinize the relevance of this concept. Moreover, we estimate that converting a small percentage of existing white fat mass in obese subjects into active brite adipocytes could be sufficient to achieve meaningful benefits in metabolism. In conclusion, novel browning agents have to be identified before adipocyte transdifferentiation can be realized as a safe and efficacious therapy.

Distinct Shades of Adipocytes Control the Metabolic Roles of Adipose Tissues: From Their Origins to Their Relevance for Medical Applications

“…The identification of specific adipose progenitors for each adipocyte subset does not exclude that under appropriate conditions, white adipocytes acquired beige adipocytes features (beiging) and vice versa (whitening). This mechanism is reviewed in [77,78].…”

Роль Основных Эффекторных Клеток Врожденной Иммунной Системы В Развитии Метавоспаления Жировой Ткани При Ожирении

“…У даний час за морфологічними і функціональними характеристиками розрізняють чотири типи жирових клітин: білі, рожеві, бурі та бежеві адипоцити (рис. 1) [58,71].…”

“…Бежевий адипоцит має найвищу метаболічну активність серед всіх чотирьох типів адипоцитів і здатність виділяти тепло завдяки великій кількості мітохондрій. Усі типи жирових клітин мають ендокринну активність: білі адипоцити продукують низку адипокінів, які впливають на харчову поведінку (лептин) і обмін речовин (наприклад, адипонектин, резистин, адипсин); бурі адипоцити секретують гормони і фактори росту (бетатрофін і FGF21); рожеві адипоцити -компоненти молока і лептин [17,18,22,43,58,75].…”

Fibroblast growth factor inducedUcp1expression in preadipocytes requires PGE2 biosynthesis and glycolytic flux

“…6,7 In the light of these findings, the presence of active BAT in humans has garnered much interest due to its therapeutic implication in combatting the global obesity pandemic. 4,[8][9][10] Ucp1 gene expression in brown/beige adipocytes cells is tightly regulated by transcriptional networks governed by adipogenic and thermogenic regulators such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancerbinding proteins (C/EBPs), PR domain-containing protein 16 (PRDM16) and proliferator-activated receptor gamma coactivator 1-alpha (PGC1a). 1,11 The canonical signaling pathway to induce thermogenic activity and differentiation is initiated by binding of noradrenaline to the β3-adrenoreceptor, but other endogenous hormones have been studied, including the endocrine acting fibroblast growth factor 21 (FGF21).…”

“…Their functional, cellular entities are the brown and beige adipocyte, respectively. [3][4][5] Brown and beige adipocytes are characterized by multilocular lipid droplets, high mitochondrial content and high abundance of the heat producing protein Uncoupling protein 1 (UCP1). Residing in the mitochondrial inner membrane, UCP1 dissipates the proton gradient generated by the electron transport chain, thus uncoupling ATP production from oxygen consumption.…”