A high-fat diet impairs reproduction by decreasing the IL1\u03b2 level in mice treated at immature stage

Jun Li,Jie Zhang,Guizen Huang,Jie Ao,Nini An,Lugang Huang,Ping Lin,Di Gong,Fei Li,Lei Kang,Haoze Tan,Miao Yuan,Kai Li,Yanyan Li

doi:10.1038/s41598-017-00505-0

Abstract

Obesity causes low-grade inflammation that is involved in male infertility. Interleukin 1 beta (IL1β) plays an important role in this process. A high-fat diet (HFD) is the most common cause of obesity. However, the effect of a HFD on IL1β and its consequence in reproduction remain unclear. We established a HFD model in mice treated at immature stage (mice-TIS) and mice treated at mature stage (mice-TMS). Surprisingly, we found that a HFD decreased IL1β levels and was accompanied by an increase in testosterone in mice-TIS, while the reverse results were observed in mice-TMS. In addition, a HFD caused a reduction in testis macrophages and in the expression of inflammasome-related genes and proteins in mice-TIS. Furthermore, we found that IL1β inhibited testosterone secretion through down-regulating the gene expression of P450SCC and P450c17. However, the influence on mice-TIS that were induced by a HFD was recovered by stopping the HFD. In this study, we are the first to report that a HFD impairs the reproductive system by decreasing IL1β and enhancing testosterone levels in mice-TIS, which are different from the effects in mice-TMS. This provides new ideas for the treatment of obesity-induced infertility.

Highlights

Childhood overweight and obesity, a result of relative overnutrition and a sedentary life style, has become a major health concern in recent decades
The bodyweight (BW) and the ratio of epididymal adipose tissue (EAT)/bodyweight were significantly elevated in Group 4H (G4H) and Group 8C4H (G8C4H) groups compared to Group 4C (G4C) and Group 12C (G12C) groups (Fig. 1A,B), whereas both G4H and G8C4H mice had lower food intake compared to G4C and G12C mice (Fig. 1C)
After HE staining of testes, the number of germ cells, including spermatogonia, spermatocytes and spermatids, in testes were counted to assess the influence of a high-fat diet (HFD) on mouse reproduction

Summary

Introduction

A result of relative overnutrition and a sedentary life style, has become a major health concern in recent decades. IL1β is a pro-inflammatory cytokine that stimulates the secretion of multiple cytokines/chemokines, including IL6, IL8, IL10, IL13, MCP-4 and TNFα7. It is produced mainly by monocytes and macrophages through the inflammasome pathway. Leydig cells are located within the interstitial compartment of the testes and are responsible for the production of androgens and other hormones, including testosterone, androstenedione and dehydroepiandrosterone, which play an important role in normal masculinization, development of the testes, maintenance of spermatogenesis and general male fertility[13,14,15]. Little is known about the role of IL1β in the reproductive system of overweight or obese children and the mechanism of HFD-induced changes in the IL1β level in testes. We observed the restoration of HFD mice testes after stopping the HFD

Methods

Results

Conclusion