Bortolotti Murielle, Kreis Roland, Debard Cyrille, Cariou Bertrand, Faeh David, Chetiveaux Maud, Ith Michael, Vermathen Peter, Stefanoni Nathalie, Lê Kim-Anne, Schneiter Philippe, Krempf Michel, Vidal Hubert, Boesch Chris, Tappy Luc
Department of Physiology, University of Lausanne, Lausanne, Switzerland.
Am J Clin Nutr. 2009 Oct;90(4):1002-10. doi: 10.3945/ajcn.2008.27296. Epub 2009 Aug 26.
High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown.
The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men.
Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens.
The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14).
Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.
已知高糖和高脂肪摄入会增加肝细胞内脂质（IHCLs）并导致胰岛素抵抗。高蛋白摄入可能有助于胰岛素抵抗患者减轻体重并改善葡萄糖稳态，但其对IHCLs的影响尚不清楚。
评估高蛋白摄入对健康年轻男性高脂肪饮食诱导的IHCL积累和胰岛素敏感性的影响。
10名志愿者采用交叉设计进行研究，分别接受4天的高热量高脂肪（HF）饮食、高热量高脂肪高蛋白（HFHP）饮食或对照等热量（对照）饮食。通过氢磁共振波谱法测量IHCLs，通过间接测热法测量空腹代谢，通过高胰岛素-正常血糖钳夹法测量胰岛素敏感性，通过酶联免疫吸附测定法和气相色谱-质谱法测量血浆浓度；在皮下脂肪组织活检标本中评估关键脂肪生成基因的表达。
HF饮食使IHCLs增加90±26%，血浆组织型纤溶酶原激活物抑制剂-1（tPAI-1）增加54±11%（两者P<0.02），并使血浆游离脂肪酸降低26±11%，β-羟基丁酸降低61±27%（两者P<0.05）。HFHP饮食减弱了IHCLs的增加，并使血浆β-羟基丁酸和tPAI-1浓度恢复正常。胰岛素敏感性未改变，而固醇调节元件结合蛋白-1c和关键脂肪生成基因的表达在HF和HFHP饮食后增加（P<0.02）。HF饮食后胆汁酸浓度保持不变，但HFHP饮食后增加了50±24%（P=0.14）。
蛋白质摄入通过可能在肝脏水平发挥的作用，显著减弱了HF饮食对IHCLs和tPAI-1的影响。可能涉及蛋白质诱导的胆汁酸浓度增加。该试验已在www.clinicaltrials.gov注册，注册号为NCT00523562。
