High-fat diet (HFD) impairs female reproductive function, while conjugated linoleic acid (CLA) has been demonstrated to alleviate HFD-induced obesity. The purpose of this study is to explore the role and mechanism of CLA in regulating HFD-induced female reproductive impairment. CLA mitigated HFD-impaired female reproductive function and improved glucose homeostasis, accompanied with altered gut microbiota composition. Fecal microbiota transplantation (FMT) from CLA-treated donors reproduced the reproductive benefits, while antibiotics treatment abolished them, highlighting the essential role of gut microbiota. Moreover, both CLA and FMT activated brown adipose tissue (BAT) thermogenesis, whereas BAT removal eliminated their beneficial effects on reproductive function. Mechanistically, CLA and FMT enhanced leptin signaling in the hypothalamus-pituitary-ovary axis, whereas these effects were abolished by antibiotics treatment, BAT removal, or leptin deficiency. Collectively, our findings demonstrate that CLA rescues HFD-induced female reproductive impairment through the gut microbiota-BAT-leptin axis. These findings provide reference for applying CLA or targeting gut microbiota-BAT-leptin axis in alleviating the reproductive impairment of obese females.
Fu et al. (Wed,) studied this question.