Endocrine Abstracts (2011) 26 P129

Extreme ketogenic, but not moderate, low-carbohydrate/high fat diets lead to loss of lean body mass in rats due to impairments of the GH/IGF system

M Bielohuby1, M Sawitzky2, B Stoehr1, J Ramisch1, D Menhofer1, A Hoeflich2 & M Bidlingmaier1

1Endocrine Research Unit, LMU, Munich, Germany; 2Laboratory of Mouse Genetics, FBN, Dummerstorf, Germany.

In rats, we have previously demonstrated that consumption of low-carbohydrate/high-fat diets (LC–HFD) led to significant reductions in circulating IGF1. We further observed that rats fed an extreme, ketogenic, but comparably low protein LC–HFD (LC–HF-2) showed loss of bodyweight, which was mainly due to loss of lean body mass (LBM). Consumption of a moderate protein LC–HF diet (LC–HF-1) did not affect LBM acquisition compared to controls. We now investigated whether the effects on LBM could be explained by specific differences in muscle growth regulation through the local GH/IGF system.

Methods: We pair-fed 12-week old Wistar rats either a control chow (CH), LC–HF-1 or LC–HF-2 diets (n=8/diet group). After 3 weeks, GH profiles were determined by immunoassay using samples from serial blood samplings (n=80/diet group). After 4 weeks rats were sacrificed to analyze muscle samples (M. quadriceps femuris) by quantitative real-time PCR and Western blot analyses.

Results: Circulating IGF1 was lower in both LC–HF groups compared to CH. GH medians were significantly increased with LC–HF-1 (P<0.05), but unchanged in the LC–HF-2 group. Muscle GH-receptor mRNA expression was unaffected in both LC–HFD groups. Muscle IGF1 mRNA expression was increased in rats fed LC–HF-1 (+110%, P<0.05). High expression of IGF-I in muscle resulted in a specific activation of IGF1 receptor signalling pathways. Phosphorylation of AKT (+110%, P<0.001) and GSK3β (+54%, P<0.05) were higher in muscles of rats fed the LC–HF-1 diet.

In conclusion, our data suggest that loss of LBM with LC–HF-1 was prevented by the rise in pituitary GH secretion, which might be triggered by low liver-derived IGF1 concentrations. With LC–HF-1, higher GH secretion resulted in increased muscle IGF1 activation of associated signalling pathways. In contrast, rats fed the ketogenic LC–HF-2 diet showed unchanged muscle IGF1 expression and loss of LBM, probably due to lower systemic IGF1 levels and normal pituitary GH output.

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