Three Weeks on a High-Fat Diet Increases Intrahepatic Lipid Accumulation and Decreases Metabolic Flexibility in Healthy Overweight Men

Department of Human Biology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 04/2011; 96(4):E691-5. DOI: 10.1210/jc.2010-2243
Source: PubMed

ABSTRACT In rodents, high-fat diets increase intrahepatic lipid (IHL), but human studies are scarce.
Our objective was to examine whether high-fat diets influence IHL, intramyocellular lipids (IMCL), and insulin resistance.
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.
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.
A 3-wk high-fat diet leads to IHL accumulation and a decreased metabolic flexibility, but insulin sensitivity is unaffected.

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