High protein intake reduces intrahepatocellular lipid deposition in humans2

• Published in: The American journal of clinical nutrition 2009-10, Vol.90 (4), p.1002-1010
• Main Authors: 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
• Format: Article
• Language: English
• ISSN: 0002-9165; 1938-3207
• DOI: 10.3945/ajcn.2008.27296

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–induced 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–mass 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 β-hydroxybutyrate by 61 ± 27% (P< 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma β-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.govas NCT00523562.