title: FoxO1 interacts with transcription factor EB and differentially regulates mitochondrial uncoupling proteins via autophagy in adipocytes.
abstract: Mitochondrial uncoupling proteins (UCPs) are inducible and play an important role in metabolic and redox homeostasis. Recent studies have suggested that FoxO1 controls mitochondrial biogenesis and morphology, but it remains largely unknown how FoxO1 may regulate mitochondrial UCPs. Here we show that FoxO1 interacted with transcription factor EB (Tfeb), a key regulator of autophagosome and lysosome, and mediated the expression of UCP1, UCP2 and UCP3 differentially via autophagy in adipocytes. UCP1 was down-regulated but UCP2 and UCP3 were upregulated during adipocyte differentiation, which was associated with increased Tfeb and autophagy activity. However, inhibition of FoxO1 suppressed Tfeb and autophagy, attenuating UCP2 and UCP3 but increasing UCP1 expression. Pharmacological blockade of autophagy recapitulated the effects of FoxO1 inhibition on UCPs. Chromatin immunoprecipitation assay demonstrated that FoxO1 interacted with Tfeb by directly binding to its promoter, and silencing FoxO1 led to drastic decrease in Tfeb transcript and protein levels. These data provide the first line of evidence that FoxO1 interacts with Tfeb to regulate autophagy and UCP expression in adipocytes. Dysregulation of FoxO1→autophagy→UCP pathway may account for metabolic changes in obesity.
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Longhua
authors: L
authors: Liu
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Zhipeng
authors: Z
authors: Tao
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Louise D
authors: LD
authors: Zheng
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Joseph P
authors: JP
authors: Brooke
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Cayleen M
authors: CM
authors: Smith
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Dongmin
authors: D
authors: Liu
authors: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore , Singapore.
authors: Yun Chau
authors: YC
authors: Long
authors: Department of Human Nutrition, Foods and Exercise, Virginia Tech, Fralin Life Science Institute, College of Agriculture and Life Science , Blacksburg, VA, USA.
authors: Zhiyong
authors: 0000-0001-7615-9788
authors: Z
authors: Cheng