A Low Fat, Weight-Stable, Diet Decreases Oxidative Stress In Overweight/Obese Subjects Without Changing Liver Fat or Insulin Sensitivity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 723-745-Lipids: Fatty Liver Disease & Lipodystrophies
Basic/Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-731
Seda Suvag1, Anna L. Marina1, Holly S. Callahan2 and Kristina M. Utzschneider*1
1VA Puget Sound Healthcare System, Seattle, WA, 2University of Washington, Seattle, WA
Dietary fat, insulin resistance and oxidative stress have all been hypothesized to contribute to the development of non-alcoholic fatty liver disease and its progression to steatohepatitis. We determined under weight-stable conditions the effects of dietary fat composition on liver fat, insulin sensitivity (Si) and markers of oxidative stress in overweight/obese subjects with normal glucose tolerance and normal liver enzymes. Subjects consumed a control diet (CD: 35% energy from fat/12% saturated fat, 18% protein, 47% carbohydrate) for 10 days, followed by a low fat diet (LFD: 20% fat/8% saturated fat, 18% protein, 62% carbohydrate) or a high fat diet (HFD: 55% fat/25% saturated fat, 18% protein, 27% carbohydrate) for 4 weeks. Ten subjects completed the LFD (9 M/1 F, age 38.7±10.4 y, BMI 33.1±3.0 kg/m2, mean±SD) and 10 the HFD (7 M/3 F, 35.6±9.1 y, 34.1±5.2 kg/m2). Liver fat was quantified by MRS and hepatic and peripheral Si by a two-step hyperinsulinemic-euglycemic clamp. Urinary F2-isoprostanes were measured by GC/MS as a marker of oxidative stress. Weight of the subjects remained stable. Liver fat did not change significantly on either diet (CD: 9.4±7.5 to LFD: 7.2±7.7%, p=0.1 and CD: 8.3±7.9 to HFD: 7.0±7.2%, p=0.1). There was no change in hepatic Si, measured by the ability of low dose insulin to suppress endogenous glucose production (EGP), (CD: 58.9±11.6 to LFD: 58.1±19.9%, p=0.9 and CD: 62.1±32.1 to HFD: 54.5±20.7%, p=0.4), or the basal hepatic insulin resistance index (EGP x fasting insulin: CD: 11.7±5.0 to LFD: 12.1±5.4 g/kg lean mass/min·pM insulin, p=0.8 and CD: 15.2±11.2 to HFD: 12.4±11.2, p=0.5). Furthermore, peripheral Si, measured by the glucose infusion rate adjusted for insulin (M/I), also did not change (low dose insulin: CD: 0.07±0.1 to LFD: 0.08±0.1 mg/min/kg/pM, p=0.6 and CD: 0.11±0.1 to HFD: 0.09±0.1, p=0.4 and high dose insulin: CD: 0.28±0.2 to LFD: 0.28±0.2 mg/min/kg/pM, p=0.9 and CD: 0.34±0.3 to HFD: 0.30±0.2, p=0.3). In contrast, urinary F2-isoprostanes decreased in 9 out of 10 subjects on the LFD (CD: 2.92±1.73 to LFD: 1.88±1.85 ng/ml, p=0.01), but remained unchanged on the HFD (CD: 2.70±1.84 to HFD: 2.63±1.74 ng/ml, p=0.8). We conclude that in otherwise healthy overweight/obese subjects dietary fat content in the absence of weight change is not a major factor in the development of liver fat or insulin resistance. However, a diet low in fat and saturated fat may be protective against steatohepatitis by decreasing oxidative stress.

Nothing to Disclose: SS, ALM, HSC, KMU

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