title: High protein intake reduces intrahepatocellular lipid deposition in humans.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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 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).
  
  
  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.
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Murielle
authors.initials: M
authors.lastname: Bortolotti
authors.forename: Roland
authors.initials: R
authors.lastname: Kreis
authors.forename: Cyrille
authors.initials: C
authors.lastname: Debard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cariou
authors.forename: David
authors.initials: D
authors.lastname: Faeh
authors.forename: Maud
authors.initials: M
authors.lastname: Chetiveaux
authors.forename: Michael
authors.initials: M
authors.lastname: Ith
authors.forename: Peter
authors.initials: P
authors.lastname: Vermathen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Stefanoni
authors.forename: Kim-Anne
authors.initials: KA
authors.lastname: Lê
authors.forename: Philippe
authors.initials: P
authors.lastname: Schneiter
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Chris
authors.initials: C
authors.lastname: Boesch
authors.forename: Luc
authors.initials: L
authors.lastname: Tappy
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D002149:Energy Intake; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D004041:Dietary Fats; D004044:Dietary Proteins; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D051780:Sterol Regulatory Element Binding Protein 1; D010959:Tissue Plasminogen Activator; D020155:3-Hydroxybutyric Acid