title: High-Fructose Intake Impairs the Hepatic Hypolipidemic Effects of a High-Fat Fish-Oil Diet in C57BL/6 Mice.
abstract: BACKGROUND
  Overnutrition of saturated fats and fructose is one of the major factors for the development of nonalcoholic fatty liver disease. Because omega-3 polyunsaturated fatty acids (n-3fa) have established lipid lowering properties, we tested the hypothesis that n-3fa prevents high-fat and fructose-induced fatty liver disease in mice.
  
  
  METHODS
  Male C57BL/6J mice were randomly assigned to one of the following diet groups for 14 weeks: normal diet (ND), high-fat lard-based diet (HFD), HFD with fructose (HFD + Fru), high-fat fish-oil diet (FOD), or FOD + Fru.
  
  
  RESULTS
  Despite for the development of obesity and insulin resistance, FOD had 65.3% lower (P< 0.001) hepatic triglyceride levels than HFD + Fru, which was blunted to a 38.5% difference (P= 0.173) in FOD + Fru. The lower hepatic triglyceride levels were associated with a lower expression of lipogenic genes LXRα and FASN, as well as the expression of genes associated with fatty acid uptake and triglyceride synthesis, CD36 and SCD1, respectively. Conversely, the blunted hypotriglyceride effect of FOD + Fru was associated with a higher expression of CD36 and SCD1.
  
  
  CONCLUSIONS
  During overnutrition, a diet rich in n-3fa may prevent the severity of hepatic steatosis; however, when juxtaposed with a diet high in fructose, the deleterious effects of overnutrition blunted the hypolipidemic effects of n-3fa.
authors.affiliation: Exercise Biochemistry and Physiology Laboratory, Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL 62026-1126, United States.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Wooten
authors.affiliation: Exercise Biochemistry and Physiology Laboratory, Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL 62026-1126, United States.
authors.forename: Tayler N
authors.initials: TN
authors.lastname: Nick
authors.affiliation: Exercise Biochemistry and Physiology Laboratory, Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL 62026-1126, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Seija
authors.affiliation: Exercise Biochemistry and Physiology Laboratory, Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL 62026-1126, United States.
authors.forename: Kaylee E
authors.initials: KE
authors.lastname: Poole
authors.affiliation: Exercise Biochemistry and Physiology Laboratory, Department of Applied Health, Southern Illinois University Edwardsville, Edwardsville, IL 62026-1126, United States.
authors.forename: Kelsey B
authors.initials: KB
authors.lastname: Stout
keywords: ACC1, acetyl-CoA carboxylase-1; CPT1a, carnitine palmitoyltransferase 1a; ChREBP, carbohydrate response element binding protein; FASN, fatty acid synthase; FFA, free fatty acid; LPL, lipoprotein lipase; LXRα, liver-X-receptor; MTTP, microsomal triglyceride transfer protein; NAFLD, nonalcoholic fatty liver disease; PPARα, peroxisome proliferator activated receptor α; PPARγ, peroxisome proliferator activated receptor γ; SCD1, stearoyl-CoA desaturase 1; SREBP1c, sterol response element binding protein; T2DM, type 2 diabetes mellitus; TRL, triglyceride-rich lipoproteins; VLDL, very low-density lipoprotein; fructose; lipid metabolism; lipotoxicity; n-3fa, omega-3 polyunsaturated fatty acids; omega-3 polyunsaturated fatty acids; overnutrition