High dietary protein decreases fat deposition induced by high-fat and high-sucrose diet in rats

High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma ß-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver.众所周知，在高碳水化合物饮食与西式饮食的背景下，高蛋白饮食可降低体脂堆积。然而，鲜有研究探讨高蛋白摄入对高蔗糖（high-sucrose, HS）饮食诱导的脂肪生成，或高脂喂养诱导的脂肪沉积的特异性影响。本研究旨在明确高蛋白摄入对高脂和/或HS喂养所致脂肪沉积与脂肪分布变化的影响。本研究共纳入30只成年雄性Wistar大鼠，将其分为6组饮食干预方案，各组的蛋白质、蔗糖与脂肪含量分别设置为低、高两个水平，干预周期为5周。每周记录大鼠的体重（Body Weight, BW）与食物摄入量。分别于干预第4周和第5周开展口服葡萄糖耐量试验与进餐耐量试验。实验结束时，让大鼠摄入定量校准餐后2小时后实施安乐死，采集血液、组织与器官样本，用于分析循环代谢物、激素水平、身体成分，以及肝脏与脂肪组织的mRNA表达情况。经过5周的饮食干预后，大鼠的累计能量摄入与体重增长未出现显著变化。但高蛋白饮食可使HS饮食与高蔗糖高脂（high-sucrose high-fat, HS-HF）饮食诱导的体脂堆积增幅降低20%。基因表达与转录组分析结果显示，高蛋白摄入可通过下调脂肪酸合酶（fatty acid synthase, fasn）、乙酰辅酶A羧化酶α与β（acetyl-CoA carboxylase a and b, Acaca和Acacb）以及固醇调节元件结合转录因子1c（sterol regulatory element binding transcription factor 1c, Srebf-1c）的mRNA表达水平，降低肝脏的脂肪生成能力。此外，以血浆β-羟基丁酸水平为指标的酮体生成情况显示，同时摄入高蛋白的HS-HF喂养大鼠的酮体生成水平更高。综上，上述结果表明，高蛋白饮食可通过抑制肝脏脂肪生成并刺激酮体生成，从而降低体脂堆积。