TY - JOUR
T1 - Loss of DJ-1 promotes browning of white adipose tissue in diet-induced obese mice
AU - Silvester, Allwin Jennifa
AU - Aseer, Kanikkai Raja
AU - Jang, Hyun Jun
AU - Ryu, Ri
AU - Kwon, Eun Young
AU - Park, Jae Gyu
AU - Cho, Kiu Hyung
AU - Chaudhari, Harmesh N.
AU - Choi, Myung Sook
AU - Suh, Pann Ghill
AU - Yun, Jong Won
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11
Y1 - 2018/11
N2 - The seminal discovery of browning of white adipose tissue (WAT) holds great promise for the treatment of obesity and metabolic syndrome. DJ-1 is evolutionarily conserved across species, and mutations in DJ-1 have been identified in Parkinson's disease. Higher levels of DJ-1 are associated with obesity, but the underlying mechanism is less understood. Here, we report the previously unappreciated role of DJ-1 in white adipocyte biology in mature models of obesity. We used DJ-1 knockout (KO) mouse models and wild-type littermates maintained on a normal diet or high-fat diet as well as in vitro cell models to show the direct effects of DJ-1 depletion on adipocyte phenotype, thermogenic capacity, fat metabolism, and microenvironment profile. Global DJ-1 KO mice show increased sympathetic input to WAT and β3-adrenergic receptor intracellular signaling, leading to a previously unrecognized compensatory mechanism through browning of WAT with associated characteristics, including high mitochondrial contents, reduced lipid accumulation, adequate vascularization and attenuated autophagy. DJ-1 KO mice had normal body weight, energy balance, and adiposity, which were associated with protective effects on healthy WAT expansion by hyperplasia. Our findings revealed that browning of inguinal WAT occurred in DJ-1 KO mice that do not show increased predisposition to obesity and suggest that such potential mechanism may overcome the adverse metabolic consequences of obesity independent of an effect on body weight. Here, we provide the first direct evidence that targeting DJ-1 in adipocyte metabolic health may offer a unique therapeutic strategy for the treatment of obesity.
AB - The seminal discovery of browning of white adipose tissue (WAT) holds great promise for the treatment of obesity and metabolic syndrome. DJ-1 is evolutionarily conserved across species, and mutations in DJ-1 have been identified in Parkinson's disease. Higher levels of DJ-1 are associated with obesity, but the underlying mechanism is less understood. Here, we report the previously unappreciated role of DJ-1 in white adipocyte biology in mature models of obesity. We used DJ-1 knockout (KO) mouse models and wild-type littermates maintained on a normal diet or high-fat diet as well as in vitro cell models to show the direct effects of DJ-1 depletion on adipocyte phenotype, thermogenic capacity, fat metabolism, and microenvironment profile. Global DJ-1 KO mice show increased sympathetic input to WAT and β3-adrenergic receptor intracellular signaling, leading to a previously unrecognized compensatory mechanism through browning of WAT with associated characteristics, including high mitochondrial contents, reduced lipid accumulation, adequate vascularization and attenuated autophagy. DJ-1 KO mice had normal body weight, energy balance, and adiposity, which were associated with protective effects on healthy WAT expansion by hyperplasia. Our findings revealed that browning of inguinal WAT occurred in DJ-1 KO mice that do not show increased predisposition to obesity and suggest that such potential mechanism may overcome the adverse metabolic consequences of obesity independent of an effect on body weight. Here, we provide the first direct evidence that targeting DJ-1 in adipocyte metabolic health may offer a unique therapeutic strategy for the treatment of obesity.
KW - Autophagy
KW - Browning
KW - DJ-1
KW - Mitochondria
KW - Obesity
KW - White adipose tissue
UR - http://www.scopus.com/inward/record.url?scp=85052219409&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2018.07.004
DO - 10.1016/j.jnutbio.2018.07.004
M3 - Article
C2 - 30189364
AN - SCOPUS:85052219409
SN - 0955-2863
VL - 61
SP - 56
EP - 67
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
ER -