Blocking FSH induces thermogenic adipose tissue and reduces body fat

Nature. 2017 Jun 1;546(7656):107-112. doi: 10.1038/nature22342. Epub 2017 May 24.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • 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
  • Diet, High-Fat / adverse effects
  • Female
  • Follicle Stimulating Hormone, beta Subunit / antagonists & inhibitors*
  • Follicle Stimulating Hormone, beta Subunit / immunology
  • Haploinsufficiency
  • Male
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Obesity / drug therapy
  • Obesity / prevention & control
  • Osteoporosis / drug therapy
  • Ovariectomy
  • Oxygen Consumption / drug effects
  • Receptors, FSH / antagonists & inhibitors
  • Receptors, FSH / genetics
  • Receptors, FSH / metabolism
  • Thermogenesis* / drug effects
  • Uncoupling Protein 1 / biosynthesis

Substances

  • Antibodies
  • Follicle Stimulating Hormone, beta Subunit
  • Receptors, FSH
  • Ucp1 protein, mouse
  • Uncoupling Protein 1