Regulation of Body Composition and Bioenergetics by Estrogens

Pelt, Rachael E. Van; Gavin, Kathleen M.; Kohrt, Wendy M.

doi:10.1016/j.ecl.2015.05.011

Cited by 80 publications

(76 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This clinical phenotype has often been documented in rodents post-ovariectomy, as well as in chronic hypoestrogenemic models, such as in female Erα −/− , aromatase −/− and Fshr −/− mice 4, 16–18 , although in our hands, female Fshr −/− mice are not obese. While in female mice, genetic Fshr deficiency does not seem to protect against the pro-adiposity effects of severe chronic hypoestrogenemia, we questioned whether acute suppression of Fsh by an Fsh Ab can, through parallel mechanisms, not only attenuate bone loss 6 , but also reduce body fat and improve energy homeostasis.…”

Section: Fsh Ab Reduces Adiposity In Ovariectomized Micesupporting

confidence: 48%

“…There is also a sharp increase in visceral adiposity during this life stage, which coincides with the emergence of disrupted energy balance and reduced physical activity 3 . While the subsequent decline in estrogen explains menopausal bone loss in large part, effects of estrogen deprivation on visceral fat and whole body metabolism remain less clear 4 . We therefore questioned whether, by targeting FSH, we could not only prevent bone loss, but also reduce visceral adiposity and improve energy homeostasis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Liu

Yuen

et al. 2017

Nature

281

280

View full text Add to dashboard Cite

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.

show abstract

Section: Fsh Ab Reduces Adiposity In Ovariectomized Micesupporting

confidence: 48%

mentioning

confidence: 99%

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Liu

Yuen

et al. 2017

Nature

281

280

View full text Add to dashboard Cite

show abstract

“…Ovariectomized animals present body weight gain and excessive feeding. The treatment of ovariectomized animals with estrogen prevents these changes, and these effects are mediated, in large part, through ERα (34,35). The present study demonstrated that the uterine weight of the rats that were administered YCJ at a dose equivalent to 75 ml/kg/day was not significantly different from that of the rats that were not administered YCJ.…”

Section: Weeks 12 Weeks ---------------------------------------------supporting

confidence: 50%

Long-term supplementation with young coconut juice does not prevent bone loss but rather alleviates body weight gain in ovariectomized rats

et al. 2017

View full text Add to dashboard Cite

Abstract. Young coconut (Cocos nucifera Linn.) juice (YCJ) has traditionally been consumed to alleviate symptoms associated with the menopause. Recently, the authors demonstrated that short-term (6-week) YCJ supplementation to ovariectomized rats resulted in increased bone mass and bone formation parameter, suggesting that YCJ consumption has a positive effect on bone metabolism and may represent an intervention to help slow the bone loss during menopause transition. The present study sought to determine how long-term (12-week) YCJ supplementation affects bone metabolism in ovariectomized rats, to investigate whether such supplementation may be helpful to in osteoporosis treatment. Ten-week-old female Wistar rats were subjected to either a sham operation (Sham) or bilateral ovariectomy (Ovx). The Ovx+YCJ group received 5X-concentrated YCJ at a dose of 15 ml/kg/day for 12 weeks. Rats in the Ovx group had significantly lower femur bone mineral density than those in the Sham group. YCJ supplementation did not significantly affect this difference. However, YCJ prevented the increase in bone area of the mid third of the femur, a site high in cortical bone, and body weight gain observed following Ovx. Our findings indicate that long-term YCJ intake does not alter bone loss, but rather alleviates body weight gain following menopause.

show abstract

“…Of note is that the FSH antibodies, at the dosages used, do not affect serum estrogen levels (12,15), but this does not rule out equally relevant effects of estrogen on both bone mass and body fat (7,(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…This reduced bone mass is also accompanied by increases in visceral adiposity, a disruption of energy metabolism, and decreased physical activity (5,6). These aberrations have been shown, in clinical studies, to be reversed by pharmacologic doses of estrogen (7).…”

Section: Introductionmentioning

confidence: 99%

Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Liu

Yuen

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Pituitary hormones have long been thought solely to regulate single targets. Challenging this paradigm, we discovered that both anterior and posterior pituitary hormones, including FSH, had other functions in physiology. We have shown that FSH regulates skeletal integrity, and, more recently, find that the inhibition of FSH reduces body fat and induces thermogenic adipose tissue. A polyclonal antibody raised against a short, receptor-binding epitope of FSHβ was found not only to rescue bone loss post-ovariectomy, but also to display marked anti-obesity and pro-beiging actions. Questioning whether a single agent could be used to treat two medical conditions of public health importance -osteoporosis and obesity -we developed two further monoclonal antibodies, Hf2 and Mf4, against computationally defined receptor-binding epitopes of FSHβ. Hf2 has already been shown to reduce body weight, fat mass and cause beiging in mice on a high-fat diet. Here, we show that Hf2, which binds mouse Fsh in immunoprecipitation assays, also increases cortical thickness and trabecular bone volume, and microstructural parameters, in sham-operated and ovariectomized mice, noted on micro-computed tomography.This effect was largely recapitulated with Mf4, which inhibited bone resorption by osteoclasts and stimulated new bone formation by osteoblasts. These effects were exerted in the absence of alterations in serum estrogen in wild type mice. We also re-confirm the existence of Fshrs in bone by documenting the specific binding of fluorescently labeled FSH, FSH-CH, in vivo. Our study provides the framework for the future development of an FSH-based therapeutic that could potentially target both bone and fat. 3 SIGNIFICANCE STATEMENTWe have addressed the question whether osteoporosis and obesity, which often occur concurrently in postmenopausal women, can be targeted by a single agent. We have shown previously that the reproductive hormone FSH, the levels of which rise after menopause, regulates both body fat and bone mass. We now show that blocking FSH action using two purposefully designed epitope-specific antibodies protects against bone loss in mice. This positions both FSH antibodies as lead molecules for clinical development towards future use in people.

show abstract

Regulation of Body Composition and Bioenergetics by Estrogens

Cited by 80 publications

References 72 publications

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Long-term supplementation with young coconut juice does not prevent bone loss but rather alleviates body weight gain in ovariectomized rats

Epitope-specific monoclonal antibodies to FSHβ increase bone mass

Contact Info

Product

Resources

About