FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca²⁺/CREB pathway

Abstract

Increased fat mass and fat redistribution are commonly observed in aging populations worldwide. Although decreased circulating levels of sex hormones, androgens and oestrogens have been observed, the exact mechanism of fat accumulation and redistribution during aging remains obscure. In this study, the receptor of follicle-stimulating hormone (FSH), a gonadotropin that increases sharply and persistently with aging in both males and females, is functionally expressed in human and mouse fat tissues and adipocytes. Follicle-stimulating hormone was found to promote lipid biosynthesis and lipid droplet formation; FSH could also alter the secretion of leptin and adiponectin, but not hyperplasia, in vitro and in vivo. The effects of FSH are mediated by FSH receptors coupled to the Gαi protein; as a result, Ca2+ influx is stimulated, cAMP-response-element-binding protein is phosphorylated, and an array of genes involved in lipid biosynthesis is activated. The present findings depict the potential of FSH receptor-mediated lipodystrophy of adipose tissues in aging. Our results also reveal the mechanism of fat accumulation and redistribution during aging of males and females.

Follicle-stimulating hormone increases the intramuscular fat content and expression of lipid biosynthesis genes in chicken breast muscle

“…Thus, the capacity for lipid uptake by muscle tissue is a major determinant controlling IMF levels in chicken. Our results are consistent with previous reports in chicken adipocytes (Cui et al, 2012) and mice adipocytes (Liu et al, 2015) that LPL mRNA was upregulated by FSH treatment. DGAT2 is the main enzyme that catalyzes the final step in the synthesis of TG, which involves esterification of fatty acids for conversion into TG before final storage in various adipose tissues (Krag et al, 2007;Yen et al, 2008).…”

“…High levels of FSH, rather than decreased levels of sex hormones, are possibly responsible for fat accumulation and redistribution in aging populations (Liu et al, 2015). Consistent with the report by Cui et al (2012), AFW and AFP in FSH-treated chickens were significantly increased by 59.29% and 56.49%, respectively.…”

“…FAS, a downstream mediator of adipo-regulatory genes previously discussed (Yu et al, 2014), is critical for lipogenesis, and the expression of FAS was increased by FSH treatment in our study. Similar effects of FSH on FAS expression in 3T3-L1 preadipocytes and adipocytes from mice were reported by Liu et al (2015). The FAS results suggest that the ability to synthesize lipids in situ contributes partially to lipid deposition in chicken breast muscle and abdominal fat following FSH treatment.…”

“…The expression of PPARγ was increased by FSH treatment in our study. Liu et al (2015) also showed that PPARγ mRNA was upregulated by FSH stimulation in murine adipose tissue.…”

“…Lipid deposition in muscle is related to the intracellular transport of long-chain fatty acids via the adipocyte fatty acid-binding protein (A-FABP), which is also considered an indicator of total intramuscular adipocyte number (Jurie et al, 2007). The peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipose cell differentiation, playing a critical role in systemic lipid metabolism (Szanto and Nagy, 2005;Liu et al, 2015).…”