title: Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis, steatosis and liver injury.
abstract: Diets containing excess carbohydrate and fat promote hepatic steatosis and steatohepatitis in mice. Little is known, however, about the impact of specific carbohydrate/fat combinations on liver outcome. This study was designed to determine whether high-energy diets with identical caloric density but different carbohydrate and fat composition have unique effects on the liver. Four experimental diets were formulated with 60%kcal carbohydrate and 20%kcal fat, each in nearly pure form from a single source: starch-oleate, starch-palmitate, sucrose-oleate and sucrose-palmitate. The diets were fed to mice for 3 or 12 weeks for analysis of lipid metabolism and liver injury. All mice developed hepatic steatosis over 12 weeks, but mice fed the sucrose-palmitate diet accumulated more hepatic lipid than those in the other three experimental groups. The exaggerated lipid accumulation in sucrose-palmitate-fed mice was attributable to a disproportionate rise in hepatic de novo lipogenesis. These mice accrued more hepatic palmitate and exhibited more evidence of liver injury than any of the other experimental groups. Interestingly, lipogenic gene expression in mice fed the custom diets did not correlate with actual de novo lipogenesis. In addition, de novo lipogenesis rose in all mice between 3 and 12 weeks, without feedback inhibition from hepatic steatosis. The pairing of simple sugar (sucrose) and saturated fat (palmitate) in a high-carbohydrate/moderate-fat diet induces more de novo lipogenesis and liver injury than other carbohydrate/fat combinations. Diet-induced liver injury correlates positively with hepatic de novo lipogenesis and is not predictable by isolated analysis of lipogenic gene expression.
authors.affiliation: Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0410, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pierce
authors.affiliation: Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0410, USA.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Duwaerts
authors.affiliation: Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0410, USA.
authors.forename: Russell K
authors.initials: RK
authors.lastname: Soon
authors.affiliation: Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0410, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Siao
authors.affiliation: Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California San Francisco, San Francisco, CA 94143-0410, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Grenert
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, CA 94720, USA; KineMed, Inc., Emeryville, CA 94608, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Fitch
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, CA 94720, USA; KineMed, Inc., Emeryville, CA 94608, USA.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Hellerstein
authors.affiliation: KineMed, Inc., Emeryville, CA 94608, USA.
authors.forename: Carine
authors.initials: C
authors.lastname: Beysen
authors.affiliation: KineMed, Inc., Emeryville, CA 94608, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Turner
authors.affiliation: Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0410, USA. Electronic address: Jacquelyn.Maher@ucsf.edu.
authors.forename: Jacquelyn J
authors.initials: JJ
authors.lastname: Maher
mesh_terms: D000818:Animals; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake; D005234:Fatty Liver / Q000209:etiology*; D050155:Lipogenesis; D008099:Liver / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats
keywords: Fatty liver; Palmitate; Saturated fat; Steatohepatitis; Sucrose; Sugar; Triglyceride