Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets

Nov 12, 2016The Journal of nutritional biochemistry

Intermittent fasting lowers body fat but may worsen liver insulin resistance in young rats on different high-protein and high-fat diets

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Abstract

One-meal-per-day intermittent fasting with high fat diets led to increased insulin resistance in young male rats.

Male rats on high protein and intermittent fasting diets had lower fat deposits in the abdomen and legs.
Energy expenditure, particularly from fat burning, was higher in rats on intermittent fasting compared to those with ad libitum feeding.
Higher serum ghrelin levels were observed in rats on high protein intermittent fasting, correlating with increased food intake.
Rats on high fat intermittent fasting exhibited greater serum glucose levels during the early phase of an oral glucose tolerance test.
Intermittent fasting was associated with impaired insulin sensitivity and altered hepatic insulin signaling in the tested rats.
Despite lower fat mass, rats on intermittent fasting had higher glycogen storage linked to decreased glycogen breakdown enzyme activity.

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Intermittent fasting (IMF) is a relatively new dietary approach to weight management, although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague-Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups, and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0-40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young male rats. These results suggest that caution may be warranted when recommending intermittent fasting, especially one-meal-per-day fasting, for people with compromised glucose metabolism.

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Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets

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