SAT-168 - Ketogenic Diet Improves Blood Glucose and Reproductive Parameters of Obese Mice

Obesity negatively impacts overall health and reproduction in males and females by disrupting the hypothalamic-pituitary-gonadal axis and other physiological functions essential for fertility. The leptin-deficient obese mouse (ob/ob) is a well-established model of obesity-associated reproductive dysfunction and infertility, characterized by hyperglycemia, hypogonadism, reduced sperm production in males and absent estrous cycles in females. The ketogenic diet (KD), a high-fat, low-carbohydrate diet, has multiple metabolic effects which may be linked to reproductive function. Data on KD affects on ob/ob mouse reproduction are limited, therefore, this study was designed to examine the potential effects of a ketogenic diet on metabolic and reproductive parameters in obese male and female mice. Male and female ob/ob mice were fed a standard diet (SD) or ketogenic diet (KD) from five until twelve weeks of age. C57 wild type mice on SD were also included as an additional control group. At the end of the seven-week dietary intervention, mice were euthanized for collection of blood and tissues to evaluate metabolic and reproductive outcomes. Obese male mice fed SD showed significantly increased body weight and hyperglycemia compared to C57 control mice as predicted. Male ob/ob mice on KD remained obese with body weights similar to SD mice, but blood glucose levels were significantly reduced (593.5 ± 6.50 vs 294.2 ± 21 mg/dL). Similarly, obese female male mice fed SD showed significantly increased body weight and hyperglycemia compared to C57 control mice. Female ob/ob mice on KD also remained obese with body weights similar to SD mice, but with significantly lower blood glucose levels (375.5 ± 47.87 vs 242 ± 4.96 mg/dL). Compared to C57 control mice, male reproductive parameters were significantly reduced in obese mice on SD as expected. While male mice fed KD remained obese with a number of reproductive parameters significantly improved. Mean daily sperm production in single testis was 2.9 ± 0.10 x10⁶ in KD mice compared to 2.1 ± 0.26 x10⁶ in SD mice. Epididymal sperm number was 10.3 ± 1.4 ×10⁶ in SD mice compared to 24.9 ± 2.1 ×10⁶ in KD mice. Epididymal transit time was similar between C57 control mice and KD mice but significantly faster in SD obese mice. These data suggest that the altered metabolic profile of mice on a ketogenic diet may improve testicular sperm production and epididymal sperm maturation. Interestingly, these improvements occurred independently from changes in body weight or the presence of leptin, as ob/ob mice on a ketogenic diet lack this hormone and remained obese.

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