A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

ABSTRACT

PURPOSE: We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. METHODS: Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. RESULTS: The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low LFD 0.12 ± 0.11 vs. HFD -0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rd-high LFD 0.11 ± 0.37 vs. HFD -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (160), stearic (180), and palmitoleic (161n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (225n6) were strongly associated with changes in insulin sensitivity on both diets (LFD r = -0.77; p < 0.01; HFD r = -0.71; p = 0.02). CONCLUSIONS: A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. GOV IDENTIFIER NCT00930371.