(26-09-09) High protein intake reduces intrahepatocellular lipid deposition in humans1,2,3

Murielle Bortolotti, Roland Kreis, Cyrille Debard, Bertrand Cariou, David Faeh, Maud Chetiveaux, Michael Ith, Peter Vermathen, Nathalie Stefanoni, Kim-Anne L??, Philippe Schneiter, Michel Krempf, Hubert Vidal, Chris Boesch and Luc Tappy

1 From the Department of Physiology, University of Lausanne, Lausanne, Switzerland (MB, DF, NS, K-AL, PS, and LT); the Department of Clinical Research, University of Bern, Bern, Switzerland (RK, MI, PV, and CB); INSERM U870 and INRA U1235, Oullins, France/Universit?? Lyon 1, Facult?? de M??decine, Hospices Civils de Lyon, Lyon, France (CD and HV); INSERM U915, Nantes, France/Universit?? de Nantes, Facult?? de M??decine, Institut du Thorax, Nantes, France (BC, MC, and MK); and the Department of Endocrinology, Diabetes, and Metabolism, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (LT).
2 Supported by the Swiss National Science Foundation (grant 310000-109737 to LT and CB).
3 Address correspondence to L Tappy, Faculty of Biology and Medicine, Department of Physiology, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland. E-mail: [email protected] .
Background: 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.
Objective: The aim was to assess the effect of high protein intake on high-fat diet?Cinduced IHCL accumulation and insulin sensitivity in healthy young men.
Design: 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 1H-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?Cmass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens.
Results: 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 ??-hydroxybutyrate by 61 ?? 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma ??-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).
Conclusions: 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.

Source: American Journal of Clinical Nutrition, doi:10.3945/ajcn.2008.27296
Vol. 90, No. 4, 1002-1010, October 2009

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