Effect of a high-calorie diet and constant light exposure on female reproduction, metabolism and immune inflammation: A comparative study of different mouse models

Abstract

Problem: Excess caloric intake and irregular circadian rhythm could severely impair female reproductive, metabolic, and immune function. However, the similarities and differences between their individual and combined effects and mechanisms have not been fully elucidated. Due to limitations and confounding factors in clinical research, we used these two kinds of unhealthy factors to intervene the mice singly or in combination to explore their effects on individuals.

Method of study: We used a high-calorie diet (HCD), constant light exposure (CLE), and a high-calorie diet combined with constant light exposure (HCD + CLE) to build three different mouse models. During the 9 weeks modeling period, the estrous cycles were monitored, and after modeling, the indicators of glycolipid metabolism, inflammation, and reproductive endocrine function were tested.

Results: We found that both HCD and CLE alone could induce ovulatory disorders, obesity, and chronic low-grade inflammation and inhibit melatonin secretion. The difference was that HCD significantly reduced the serum luteinizing hormone (LH) and testosterone (T) levels, inhibited the expression of FSH β and LH β in pituitary, increased cytochrome P450 enzymes and LH receptor expression in ovary, as well causing impaired glucose tolerance and hyperlipidemia, and significantly promoted the secretion of leptin and inhibited the secretion of adiponectin. However, CLE significantly increased blood LH and T, prompted the expression of kisspeptin in hypothalamus and LH β in pituitary, and had no effect on glycolipid metabolic indexes or the secretion of leptin or adiponectin. The phenotype of HCD + CLE model was basically the same as that of HCD model, associated with more severe visceral obesity and chronic inflammation.

Conclusions: In conclusion, we found that unhealthy lifestyle determines the phenotype of reproductive endocrine, immune, and metabolic disorders. These findings can provide theoretical support for the subsequent study of PCOS-like features.

Keywords: chronic inflammation; constant light exposure; high-calorie diet; metabolic syndrome; mouse models; reproductive endocrinology.