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间歇性禁食可减少幼鼠体内脂肪,但无论高蛋白和高脂肪饮食如何,都会加剧其肝脏胰岛素抵抗。

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

作者信息

Park Sunmin, Yoo Kyung Min, Hyun Joo Suk, Kang Suna

机构信息

Dept. of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.

Dept. of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.

出版信息

J Nutr Biochem. 2017 Feb;40:14-22. doi: 10.1016/j.jnutbio.2016.10.003. Epub 2016 Oct 15.

DOI:10.1016/j.jnutbio.2016.10.003
PMID:27835792
Abstract

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.

摘要

间歇性禁食(IMF)是一种相对较新的体重管理饮食方法,尽管其功效和不良影响尚未完全阐明,且IMF的最佳饮食方案也尚不明确。我们检验了这样一种假设:对于因饮食导致肥胖或超重的正常年轻雄性斯普拉格-道利大鼠,采用每日一餐的高脂肪(HF)或高蛋白(HP)间歇性禁食饮食可以改变能量、脂质和葡萄糖代谢。5周龄的雄性大鼠自由采食HF(40%脂肪)或HP(26%蛋白质)饮食(AL),或在黑暗周期开始时进行3小时的进食(IMF),持续5周。HP和IMF组的附睾脂肪垫以及腿部和腹部的脂肪沉积较少。黑暗周期开始时的能量消耗,尤其是脂肪氧化产生的能量消耗,IMF组高于AL组,这可能是由于活动水平较高。IMF组的棕色脂肪含量较高。HP-IMF组的血清胃饥饿素水平高于其他组,因此,HP-IMF组的累积食物摄入量也高于HF-IMF组。在口服葡萄糖耐量试验的第一部分(0 - 40分钟),HF-IMF组的血清葡萄糖曲线下面积(AUC)较高,而IMF和HF组两部分的血清胰岛素水平AUC均较高。在腹腔注射胰岛素耐量试验中,IMF组的血清葡萄糖水平高于AL组。同样,IMF和HF组的肝脏胰岛素信号(GLUT2、pAkt)减弱,磷酸烯醇式丙酮酸羧激酶(PEPCK)表达高于其他组,并且HOMA-IR显示IMF组的胰岛素敏感性显著受损。然而,令人惊讶的是,IMF组的肝脏和骨骼肌糖原储存高于AL组。IMF组较高的糖原储存与糖原磷酸化酶的表达低于AL组有关。总之,IMF尤其是HF饮食增加了胰岛素抵抗,可能是通过减弱肝脏胰岛素信号实现的,并且尽管年轻雄性大鼠的脂肪量减少,但糖原磷酸化酶的表达降低。这些结果表明,对于葡萄糖代谢受损的人群,在推荐间歇性禁食,尤其是每日一餐禁食时,可能需要谨慎。

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