title: Comparative study of the modulation of fructose/sucrose-induced hepatic steatosis by mixed lipid formulations varying in unsaturated fatty acid content.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. NAFLD encompasses a spectrum of diseases, ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and liver failure. The etiology of NAFLD remains unclear but is thought to relate to increased fatty acid flux within the liver that results in toxic fatty acid metabolite production. One source of increased fatty acid flux is fructose/sucrose-induced hepatic lipogenesis. Current treatment for NAFLD encompasses dietary modifications. However, little scientific evidence exists on which to base many dietary recommendations, especially the intake of different types of carbohydrates and fats. We hypothesized that lipid mixtures of unsaturated fatty acids would inhibit lipogenesis and subsequent hepatic steatosis induced by high carbohydrate diets. The aim of this study was to examine the effects of different complex mixtures of fatty acids upon the development of fructose/sucrose-induced hepatic steatosis.
  
  
  METHODS
  C57BL/6 mice were randomized to normocaloric chow-based diets that varied in the type of carbohydrate (starch, sucrose, fructose). Animals in each carbohydrate group were further randomized to diets that varied in lipid type (no additional lipid, soybean oil, fish oil, olive/soybean oil, macadamia nut oil). These oils were chosen based upon their content of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, or omega-7 monounsaturated fatty acids. Fatty acid flux in the liver was determine by assessing hepatic lipid content (steatosis). We also assessed fatty acid levels in the plasma and liver of the animals, hepatic lipogenesis activity, hepatic stearoyl-CoA-1 desaturase activity, and hepatic elongase activity.
  
  
  RESULTS
  Animals consumed similar amounts of the diets and maintained normal body weights throughout the study. Both sucrose and fructose induced hepatic lipogenesis and steatosis, with fructose being more potent. All mixed lipids similarly inhibited steatosis, limiting lipid content to levels found in the control (starch) animals. Lipogenesis and stearoyl-CoA-1 desaturase activity were increased in the sucrose and fructose groups. Levels of these enzymatic processes remained at baseline in all of the lipid groups.
  
  
  CONCLUSIONS
  This is the first study to compare various complex lipid mixtures, based upon dietary oils with different types of long-chain fatty acids, upon development of sucrose/fructose-induced steatosis. Both carbohydrate source and lipid content appear important for the modulation of steatosis. Moderate intake of complex lipids with high unsaturated to saturated fatty acid ratios inhibited both lipogenesis and steatosis.
authors.affiliation: Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, Indianapolis, IN 46202 USA.
authors.forename: Rafat A
authors.initials: RA
authors.lastname: Siddiqui
authors.affiliation: Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, Indianapolis, IN 46202 USA.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, Indianapolis, IN 46202 USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Harvey
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL 60015 USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pavlina
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL 60015 USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Becker
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL 60015 USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Zaloga
keywords: Fatty acids; Fish oil; Fructose; Hepatic steatosis; Lipid emulsion; Lipogenesis; Liver; Macadamia nut oil; Non-alcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Olive oil; Parenteral-nutrition-associated liver disease (PNALD); Soybean oil; Sucrose