Distinct functions of PPARγ isoforms in regulating adipocyte plasticity.
A better understanding of the mechanisms underlying obesity and its comorbidities is key to designing new therapies and treatments. PPARγ is a master regulator of adipocyte biology but the functions of its isoforms are poorly distinguished. Here we demonstrated that PPARγ1 is preferentially expressed in catabolic fat depots while PPARγ2 presents itself at a higher level in browning-resistant depots. PPARγ2, but not PPARγ1, responds to endogenous ligands to induce adipogenesis, and the isoforms regulate distinct sets of white and brown adipocyte genes. Moreover, PPARγ1 negatively correlates while PPARγ2 positively correlates with adiposity in human subcutaneous and visceral fat. These results together indicate that PPARγ1 and PPARγ2 have distinct functions in regulating adipocyte plasticity, and future research should take into account the binary roles of both isoforms in order to identify druggable gene targets and pathways relevant for treatment of metabolic disorders.
Department of Pathology and Cell Biology, Naomi Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY, 10032, USA.
Dylan
D
Li
Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Feng
F
Zhang
Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, 10032, USA.
Xuan
X
Zhang
Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, 10032, USA.
Chenyi
C
Xue
Department of Pathology and Cell Biology, Naomi Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY, 10032, USA.
Maria
M
Namwanje
Department of Pathology and Cell Biology, Naomi Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY, 10032, USA; Department of Cardiology, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi, China.
Lihong
L
Fan
Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, 10032, USA.
Muredach P
MP
Reilly
Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Fang
F
Hu
Department of Pathology and Cell Biology, Naomi Berrie Diabetes Center, Columbia University College of Physicians & Surgeons, New York, NY, 10032, USA. Electronic address: lq2123@cumc.columbia.edu.
Li
L
Qiang
D052437:Adipocytes, Brown / Q000166:cytology* / Q000502:physiology*; D052438:Adipocytes, White / Q000166:cytology* / Q000502:physiology*; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D000066670:Cell Plasticity / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D047495:PPAR gamma; D020033:Protein Isoforms
Adipocyte; Beiging; Browning; Obesity; PPARγ; PPARγ isoforms