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 (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) 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.

Keywords: Dietary fat; High-fat diet; Insulin sensitivity; Saturated fat.

Fig. 1

Glucose (a, b) and insulin (c, d) levels were well matched during the clamps. The Rd did not change on the LFD (e) but decreased significantly on the HFD (Rd-low p = 0.03, Rd-high p = 0.05) (f). There was no difference in free fatty acid suppression after the LFD (g) and the HFD (h). Symbols: control prior to LFD open triangle and solid line; LFD solid triangle and dashed line; and control prior to HFD open circle and solid line; HFD solid circle and dashed line. Mean ± SEM, n = 10 for each diet