Excess calorie consumption, particularly of a diet high in fat, is a risk factor for both
obesity and reproductive disorders. Animal model studies indicate that elevated
dietary fat can influence some reproductive functions independent of
obesity. In the current study we sought to determine whether a high-fat diet (HFD) impacts ovarian function, long-term fertility, and local and systemic markers of
inflammation independent of
obesity. Five-week-old mice were fed either
low-fat diet (control group-LF-Ln) or HFD for 10 wk and were divided based on
body weight into high-fat obese (HF-Ob: >25 g) and high-fat lean (HF-Ln: <22 g). Ovaries were collected to assess ovarian follicles and to determine the degree of local
inflammation. Serum proinflammatory
cytokines were also measured. A group of animals was followed for breeding trials for 5 mo while being exposed to LFD or HFD. We found that both 10-wk and 32-wk exposure to HFD resulted in depleted primordial follicles regardless of
obesity phenotype. Macrophage counts revealed increased tissue
inflammation in the ovary independent of
obesity. In addition, serum proinflammatory
cytokines were increased in HF-Ln and HF-Ob in comparison to LF-Ln mice. Moreover, HFD had a sustained effect on litter production rate and number of pups per litter regardless of obese phenotype. This study describes for the first time that exposure to HFD causes significant reduction in primordial follicles, compromised fertility, produced higher proinflammatory
cytokine levels, and increased ovarian macrophage infiltration, independent of
obesity. The negative effects of HFD on primordial follicles may be mediated by increased tissue
inflammation.