极低碳水化合物、高脂肪的减肥饮食可降低肥胖大鼠肝脏基因对葡萄糖的反应。

Very low-carbohydrate, high-fat, weight reduction diet decreases hepatic gene response to glucose in obese rats.

作者信息

Axen Kathleen V, Harper Marianna A, Kuo Yu Fu, Axen Kenneth

机构信息

Department of Health and Nutrition Sciences, Brooklyn College, City University of New York, New York, USA.

出版信息

Nutr Metab (Lond). 2018 Jul 31;15:54. doi: 10.1186/s12986-018-0284-9. eCollection 2018.

DOI:10.1186/s12986-018-0284-9

PMID:31061673

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6497366/

Abstract

BACKGROUND

Very low carbohydrate (VLC) diets are used to promote weight loss and improve insulin resistance (IR) in obesity. Since the high fat content of VLC diets may predispose to hepatic steatosis and hepatic insulin resistance, we investigated the effect of a VLC weight-reduction diet on measures of hepatic and whole body insulin resistance in obese rats.

METHODS

In Phase 1, adult male Sprague-Dawley rats were made obese by ad libitum consumption of a high-fat (HF1, 60% of energy) diet; control rats ate a lower-fat (LF, 15%) diet for 10 weeks. In Phase 2, obese rats were fed energy-restricted amounts of a VLC (5%C, 65%F), LC (19%C, 55%F) or HC (55%C, 15%F) diet for 8 weeks while HF2 rats continued the HF diet ad libitum. In Phase 3, VLC rats were switched to the HC diet for 1 week. At the end of each phase, measurements of body composition and metabolic parameters were obtained. Hepatic insulin resistance was assessed by comparing expression of insulin-regulated genes following an oral glucose load,that increased plasma insulin levels, with the expression observed in the feed-deprived state.

RESULTS

At the end of Phase 1, body weight, percent body fat, and hepatic lipid levels were greater in HF1 than LF rats ( < 0.05). At the end of Phase 2, percent body fat and intramuscular triglyceride decreased in LC and HC ( < 0.05), but not VLC rats, despite similar weight loss. VLC and HF2 rats had higher HOMA-IR and higher insulin at similar glucose levels following an glucose load than HC rats ( < 0.05). HC, but not VLC or HF2 rats, showed changes in and expression ( < 0.05) in response to an oral glucose load. At the end of Phase 3, switching from the VLC to the HC diet mitigated differences in hepatic gene expression.

CONCLUSION

When compared with a high-carbohydrate, low-fat diet that produced similar weight loss, a commonly used VLC diet failed to improve whole body insulin resistance; it also reduced insulin's effect on hepatic gene expression, which may reflect the development of hepatic insulin resistance.

摘要

背景

极低碳水化合物（VLC）饮食用于促进肥胖患者的体重减轻并改善胰岛素抵抗（IR）。由于VLC饮食中的高脂肪含量可能易导致肝脂肪变性和肝脏胰岛素抵抗，我们研究了VLC减重饮食对肥胖大鼠肝脏和全身胰岛素抵抗指标的影响。

方法

在第1阶段，成年雄性Sprague-Dawley大鼠通过随意食用高脂肪（HF1，能量的60%）饮食而变得肥胖；对照大鼠食用低脂肪（LF，15%）饮食10周。在第2阶段，肥胖大鼠被给予能量限制量的VLC（5%碳水化合物，65%脂肪）、LC（19%碳水化合物，55%脂肪）或HC（55%碳水化合物，15%脂肪）饮食8周，而HF2大鼠继续随意食用HF饮食。在第3阶段，VLC大鼠改为食用HC饮食1周。在每个阶段结束时，获取身体成分和代谢参数的测量值。通过比较口服葡萄糖负荷后（这会增加血浆胰岛素水平）胰岛素调节基因的表达与禁食状态下观察到的表达，来评估肝脏胰岛素抵抗。

结果

在第1阶段结束时，HF1大鼠的体重、体脂百分比和肝脏脂质水平高于LF大鼠（<0.05）。在第2阶段结束时，尽管体重减轻相似，但LC和HC大鼠的体脂百分比和肌肉内甘油三酯下降（<0.05），而VLC大鼠则未下降。在口服葡萄糖负荷后，在相似的血糖水平下，VLC和HF2大鼠的稳态模型评估胰岛素抵抗（HOMA-IR）更高且胰岛素水平更高（<0.05）。HC大鼠，但不是VLC或HF2大鼠，在口服葡萄糖负荷后显示出相关基因表达的变化（<0.05）。在第3阶段结束时，从VLC饮食改为HC饮食减轻了肝脏基因表达的差异。