Blocking FSH induces thermogenic adipose tissue and reduces body fat

Peng Liu, Yaoting Ji, Tony Yuen, Elizabeth Rendina-Ruedy, Victoria E. DeMambro, Samarth Dhawan, Wahid Abu-Amer, Sudeh Izadmehr, Bin Zhou, Andrew C. Shin, Rauf Latif, Priyanthan Thangeswaran, Animesh Gupta, Jianhua Li, Valeria Shnayder, Samuel T. Robinson, Yue Eric Yu, Xingjian Zhang, Feiran Yang, Ping Lu, Yu Zhou, Ling-Ling Zhu, Douglas J. Oberlin, Terry F. Davies, Michaela R. Reagan, Aaron Brown, T. Rajendra Kumar, Solomon Epstein, Jameel Iqbal, Narayan G. Avadhani, Maria I. New, Henrik Molina, Jan B. van Klinken, Edward X. Guo, Christoph Buettner, Shozeb Haider, Zhuan Bian, Li Sun, Clifford J. Rosen and Mone Zaidi ()
Additional contact information
Peng Liu: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Yaoting Ji: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Tony Yuen: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Elizabeth Rendina-Ruedy: Maine Medical Center Research Institute
Victoria E. DeMambro: Maine Medical Center Research Institute
Samarth Dhawan: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Wahid Abu-Amer: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Sudeh Izadmehr: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Bin Zhou: Columbia University
Andrew C. Shin: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Rauf Latif: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Priyanthan Thangeswaran: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Animesh Gupta: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Jianhua Li: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Valeria Shnayder: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Samuel T. Robinson: Columbia University
Yue Eric Yu: Columbia University
Xingjian Zhang: Columbia University
Feiran Yang: Columbia University
Ping Lu: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Yu Zhou: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Ling-Ling Zhu: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Douglas J. Oberlin: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Terry F. Davies: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Michaela R. Reagan: Maine Medical Center Research Institute
Aaron Brown: Maine Medical Center Research Institute
T. Rajendra Kumar: University of Colorado School of Medicine
Solomon Epstein: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Jameel Iqbal: Pathology Service, Greater Los Angeles Veterans Affairs Medical Center
Narayan G. Avadhani: Deparment of Animal Biology, University of Pennsylvania School of Veterinary Medicine
Maria I. New: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Henrik Molina: Proteomics Resource Center, Rockefeller University
Jan B. van Klinken: Leiden University Medical Center
Edward X. Guo: Columbia University
Christoph Buettner: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Shozeb Haider: University College London School of Pharmacy
Zhuan Bian: School and Hospital of Stomatology, Wuhan University, and Key Laboratory of Oral Biomedicine, Ministry of Education
Li Sun: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai
Clifford J. Rosen: Maine Medical Center Research Institute
Mone Zaidi: and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai

Nature, 2017, vol. 546, issue 7656, 107-112

Abstract: Abstract Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the β-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the β-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

Date: 2017
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DOI: 10.1038/nature22342

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