Endocrine Abstracts

Metabolic diseases are among the most important diseases in western societies and usually related to obesity. Dietary interventions are recommended for treatment and include both strategies with reduced caloric intake and alterations in macronutrient composition. Metabolism must be assumed to be regulated differently in females and males. In previous studies we demonstrated that low carbohydrate high fat (LCHF) diets affect GH/IGF-I axis in male rats. We know investigated whether the same effects can be seen in females, and also included a high carbohydrate, high fat diet (HCHF) in our study. Purified diets (% of metabolizable energy, fat/protein/carbohydrate: Chow (CH, 16.7/19.0/64.3), protein matched LCHF-1 (78.7/19.1/2.2), ketogenic LCHF-2 (92.8/5.5/1.7) and HCHF (61.9/18.7/19.4)) were pair-fed isoenergetically for 4 weeks to male and female Wistar rats (12 weeks at start, n=7/group). GH secretion profiles were collected (10 samples/5 hours) after 3 weeks. At study end (6 hours fasting, dark phase), blood samples and organs were collected. Pituitary GHRHR and GH as well as liver GHR and IGF-I mRNA were analyzed. Serum GH secretion showed higher nadirs and lower peaks in females. On the ketogenic LCHF-2, GH tended to be lower in both sexes, while GH was increased on HCHF only in females. In males, IGF-I (ng/mL) was significantly reduced on all HF diets (CH: 1441±79.13, LCHF-1: 961.9***±31.48, LCHF-2: 940.2***±39.87, HCHF: 993.6***±14.78), but only on the ketogenic LCHF-2 diet in females (CH: 713.3±49.0, LCHF-1: 588.0±48.15, LCHF-2: 463.3***±34.58, HCHF: 574.4±26.4). Pituitary GH mRNA was generally higher in females, and lowest in rats of both sexes fed LCHF-2. In both sexes, GHRHR mRNA was reduced on all HF diets (males: CH: 0.07±0.01, LCHF-1: 0.04±0.01, LCHF-2: 0.04±0.01, HCHF: 0.03±0.01*; females: CH: 0.08±0.01, LCHF-1: 0.03±0.02, LCHF-2: 0.03±0.01*, HCHF: 0.04±0.01). Liver GHR mRNA tended to be lower on LCHF-1 and LCHF-2 in both sexes and increased on HCHF in females. Our data demonstrate that HF diets lead to a more pronounced deterioration of the GH/IGF-I axis in males. Whether hypothalamic or pituitary mechanisms regulating GH secretion or peripheral mechanisms regulating GH sensitivity cause the sex difference is currently studied.