Three weeks on a high-fat diet increases intrahepatic lipid accumulation and decreases metabolic flexibility in healthy overweight men

J Clin Endocrinol Metab. 2011 Apr;96(4):E691-5. doi: 10.1210/jc.2010-2243. Epub 2011 Jan 20.

Abstract

Context: In rodents, high-fat diets increase intrahepatic lipid (IHL), but human studies are scarce.

Objective: Our objective was to examine whether high-fat diets influence IHL, intramyocellular lipids (IMCL), and insulin resistance.

Design: Twenty overweight men were randomly allocated to low- or high-fat groups (age, 54.0 ± 2.3 and 56.4 ± 2.5 yr; body mass index, 29.3 ± 0.6 and 28.3 ± 0.5 kg/m(2), respectively). Both groups started with a 3-wk low-fat diet [15% energy (En%) as protein, 65 En% as carbohydrates, 20 En% as fat], after which half of the subjects switched to a 3-wk isocaloric high-fat diet (15 En% protein, 30 En% carbohydrates, 55 En% fat). After 3 and 6 wk, IHL and IMCL content were assessed by (1)H magnetic resonance spectroscopy and a muscle biopsy, and insulin sensitivity was studied using a hyperinsulinemic-euglycemic clamp. An additional liver scan was performed after 1 wk in the high-fat group.

Results: IHL decreased by 13% in the low-fat group and increased by 17% in high-fat group (P = 0.047). IMCL content was unaffected (P = 0.304). Insulin sensitivity was unaffected. At wk 3, IHL correlated negatively with insulin sensitivity (r = -0.584; P = 0.009, all subjects combined). Metabolic flexibility, defined as change in respiratory quotient upon insulin stimulation, was decreased after 3 wk of the high-fat diet (change in respiratory quotient was +0.02 ± 0.02 vs. -0.05 ± 0.1 in low-fat vs. high-fat group, P = 0.009). Basal plasma glucose increased after the high-fat diet (P = 0.038). Plasma parameters insulin, free fatty acids, high-sensitivity C-reactive protein, and liver enzymes and body weight were unaffected by diet.

Conclusion: A 3-wk high-fat diet leads to IHL accumulation and a decreased metabolic flexibility, but insulin sensitivity is unaffected.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diet, Atherogenic*
  • Diet, Fat-Restricted
  • Dietary Fats / pharmacology*
  • Eating / physiology
  • Health
  • Humans
  • Insulin Resistance / physiology
  • Lipid Metabolism / drug effects*
  • Liver / metabolism*
  • Male
  • Metabolism / drug effects*
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Overweight / metabolism*
  • Time Factors

Substances

  • Dietary Fats