title: A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.
abstract: OBJECTIVE
  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.
  NCT00930371.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. anize.frankenberg@gmail.com.|Post-Graduate Endocrinology Program, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. anize.frankenberg@gmail.com.|Endocrinology, VA Puget Sound Health Care System, 1660 S Columbian Way (151), Seattle, WA, 98108, USA. anize.frankenberg@gmail.com.
authors.forename: Anize D
authors.initials: AD
authors.lastname: von Frankenberg
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Marina
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.|Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: School of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
authors.forename: Holly S
authors.initials: HS
authors.lastname: Callahan
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.|Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.|Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Kratz
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.|Endocrinology, VA Puget Sound Health Care System, 1660 S Columbian Way (151), Seattle, WA, 98108, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Utzschneider
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D018592:Cross-Over Studies; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004043:Dietary Fiber / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D002149:Energy Intake; D005227:Fatty Acids / Q000008:administration & dosage / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D050177:Overweight / Q000097:blood*; D011446:Prospective Studies; D050151:Subcutaneous Fat / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004043:Dietary Fiber; D004044:Dietary Proteins; D005227:Fatty Acids; D008055:Lipids
keywords: Dietary fat; High-fat diet; Insulin sensitivity; Saturated fat