Blocking FSH induces thermogenic adipose tissue and reduces body fat

Abstract

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

Contemporaneous reproduction of preclinical science: a case study of FSH and fat

“…One of our laboratories (M.Z.) recently published the surprising finding that the pituitary hormone FSH (follicle‐stimulating hormone) is related to both osteoporosis and obesity . A reproductive hormone, FSH, had not previously been implicated in adipocyte biology.…”

“…M.Z. generated a polyclonal antibody that blocked FSH action on its receptor, and in doing so not only prevented bone loss but also caused a dramatic reduction in body fat and a conversion of white to beige adipose tissue in various murine models of obesity . Because the latter results were particularly novel and unexpected, instead of moving directly to publish the findings, M.Z.…”

“…Key data sets were reproduced by C.J.R in a process that lasted over 2 years, as other in vitro validation studies were added by both laboratories and the number of investigators expanded. Candid discussions about reproducibility and precision led to a consensus data set and a final manuscript published in Nature . Importantly, in the published paper, the contribution to reproducibility from each laboratory was described in a supplementary table.…”

Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity

“…Another protein associated with osteoporosis and adiposity is the follicle‐stimulating hormone (FSH) . Interestingly, a recent report by Zaidi and colleagues showed that blocking FSH function with a polyclonal antibody potently activates brown/beige fat thermogenesis and alleviates osteoporosis and visceral adiposity in mice (Liu et al, ).…”

A polymorphism in the transcriptional regulatory region strongly influences ovine FSHR mRNA decay

“…The follicle‐stimulating hormone receptor (FSHR), an important member of the glycoprotein hormone receptor (GPHR) subfamily of the G protein‐coupled receptor (GPCR) superfamily, is necessary for the action of FSH, an important component of the hypothalamic–pituitary–gonadal axis (Jiang et al, ; Liu et al, ). Similar to other glycoprotein hormones such as luteinizing hormone (LH) and thyroid‐stimulating hormone (TSH), FSH is also composed of two non‐covalently associated α and β subunits.…”