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Feeding Time Altered Intestinal Microbiota and SCFA Potentially Induce Diurnal Oscillations of Ovarian IL-17 and Influence Follicular Development in Puberty Growing Rabbits

ABSTRACT: Lifestyle factors of modern societies (i.e., disrupted feeding times and sleep) can affect microbiota and metabolic rhythms, leading to low fertility and infertility in adult females. This study investigated the crucial role of feeding time regulated rhythms of gut microbes and metabolites in pubertal follicular development in rabbits. Results demonstrated that night-restricted feeding (NRF) accelerated puberty onset, increased antral follicle, and enhanced granulosa cell proliferation while reducing apoptosis. Further ovarian transcriptome analysis revealed that feeding time regulated the IL-17 signaling pathway, with IL-17 protein exhibiting a diurnal oscillation of low during the day and high at night in the NRF group. The rhythmic IL-17 that mimics NRF stimulated the proliferation of granulosa cells and upregulated the expression of clock genes (BMAL1, CLOCK) and proliferation-related genes (WEE1) in vitro. Similar diurnal IL-17 fluctuations low during the day and high at night were observed in the colon of NRF group, along with increased concentrations of short-chain fatty acids (acetate, propionate, and butyrate acid) and higher abundance of associated microorganisms (Akkermansia and NK4A214_group) in the cecum. Our findings indicate that night-restricted feeding promotes pubertal follicular development and granulosa cell proliferation, which is associated with the diurnal oscillation of ovarian IL-17. The oscillation of IL-17 in both the ovary and colon may be linked to changes in the gut microbiota and short-chain fatty acids (SCFA) resulting from altered feeding times.

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE286500 | GEO | 2026/03/04

REPOSITORIES: GEO

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Project description:An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hr day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac “diurnal metabolic flexibility”, which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk) induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hr rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hr dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for non-oxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart.

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Feeding Time Altered Intestinal Microbiota and SCFA Potentially Induce Diurnal Oscillations of Ovarian IL-17 and Influence Follicular Development in Puberty Growing Rabbits

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