Journal Article

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Zhou, Bin, Thangeswaran, Priyanthan, Ji, Yaoting, Epstein, Solomon, Zhou, Yu, Kumar, T. Rajendra, Li, Jianhua, Avadhani, Narayan G., DeMambro, Victoria E., Robinson, Samuel T., Reagan, Michaela R., Sun, Li, Izadmehr, Sudeh, Buettner, Christoph, Rendina-Ruedy, Elizabeth, Zaidi, Mone, Liu, Peng, Gupta, Animesh, Dhawan, Samarth, Yu, Yue Eric, Shin, Andrew C., Bian, Zhuan, Iqbal, Jameel, Latif, Rauf, Oberlin, Douglas J., Haider, Shozeb, Zhang, Xingjian, Abu-Amer, Wahid, Guo, Edward X., Rosen, Clifford J., Davies, Terry F., Yuen, Tony, van Klinken, Jan B., Zhu, Ling-Ling, New, Maria I., Molina, Henrik, Yang, Feiran, Brown, Aaron, Shnayder, Valeria, Lu, Ping

2017

Overview

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. An antibody against the pituitary hormone Fsh reduces adiposity and increases thermogenesis in ovariectomized mice or mice fed a high-fat diet. Fat-reducing antibody Menopause is associated with bone loss and enhanced build-up of abdominal fat. Previously, Mone Zaidi and colleagues showed that an antibody against the pituitary hormone Fsh increases bone mass in mice. In this paper, they show that this antibody also reduces fatty tissue in mice that have had their ovaries removed or mice on a high fat diet. The anti-obesity effect is accompanied by increases in UCP1 expression and thermogenesis in brown and beige fat, increased whole-body oxygen consumption rate and physical activity. The authors suggest that these findings could open up opportunities for combined treatment of obesity and osteoporosis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/1 / 13/95 / 38 / 38/77 / 59 / 59/5 / 59/57 / 631/443/319/2723 / 631/443/63 / 692/163/2743/393 / 82 / 82/58 / Adipocytes / Adipocytes - drug effects / Adipocytes - metabolism / Adipose tissue / Adipose tissue (brown) / Adipose Tissue - drug effects / Adipose Tissue - metabolism / Adipose Tissue, Beige - drug effects / Adipose Tissue, Beige - metabolism / Adipose Tissue, White - drug effects / Adipose Tissue, White - metabolism / Adiposity - drug effects / Animals / Antibodies - immunology / Antibodies - pharmacology / Binding / Biocompatibility / Biomedical materials / Blocking / Body fat / Bone loss / Bone mass / Density / Diet, High-Fat - adverse effects / Female / Follicle Stimulating Hormone, beta Subunit - antagonists & inhibitors / Follicle Stimulating Hormone, beta Subunit - immunology / Follicle-stimulating hormone / Haploinsufficiency / Hormones / Humanities and Social Sciences / Immunoglobulins / Male / Menopause / Metabolism / Mice / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / multidisciplinary / Obesity / Obesity - drug therapy / Obesity - prevention & control / Osteoporosis / Osteoporosis - drug therapy / Ovariectomy / Oxygen Consumption - drug effects / Physiological aspects / Physiological research / Pituitary / Pituitary hormones / Receptors, FSH - antagonists & inhibitors / Receptors, FSH - genetics / Receptors, FSH - metabolism / Science / Thermogenesis / Thermogenesis - drug effects / Uncoupling Protein 1 - biosynthesis