Institute of Food, Nutrition and Health, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Cell Rep. 2018 Jan 16;22(3):760-773. doi: 10.1016/j.celrep.2017.12.067.
Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPARγ function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARγ-mediated regulation of brown fat function and activation by β-adrenergic signaling.
过氧化物酶体增殖物激活受体 (PPARs) 被认为是脂肪组织形成的主调控因子。然而,它们在调节棕色脂肪功能方面的作用尚未得到解决。为了解决这个问题,我们分别生成了棕色脂肪特异性敲除 PPARα、β/δ 和 γ 的诱导型小鼠。我们发现 PPARα 和 β/δ 对于棕色脂肪功能不是必需的。相比之下,我们可以证明,体外和体内敲除 PPARγ 会导致产热能力降低,伴随β-肾上腺素能信号的诱导能力丧失,以及从氧化脂肪酸代谢向葡萄糖利用的转变。我们确定甘油激酶 (Gyk) 是 PPARγ 功能的部分介质,并可以证明 Gyk 表达与人棕色脂肪活检中的棕色脂肪产热能力相关。因此,Gyk 可能构成了 PPARγ 介导的棕色脂肪功能调节与β-肾上腺素能信号激活之间的联系。