Comparative study of the modulation of fructose/sucrose-induced hepatic steatosis by mixed lipid formulations varying in unsaturated fatty acid content

Abstract

BackgroundNon-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.MethodsC57BL/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.ResultsAnimals 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.ConclusionThis 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.

Fructose stimulated de novo lipogenesis is promoted by inflammation

“…In contrast, a 30% sucrose drink did not reduce colon length or TJP mRNAs and barely increased ER stress markers (Extended Data Fig.3g-i). These results are consistent with the weaker effect of sucrose vs. fructose on hepatic steatosis 24 Colonic shortening is a sign of inflammation. To explore a plausible cause of mucosal inflammation, which can downregulate TJPs 25 , we posited that the fructose metabolite F1P…”

Study on The Effect of Different Type of Sugar on Lipid Deposition in Goose Fatty Liver

“…Some studies believe that high-dose fructose and sucrose foods can signi cantly increase liver fat content. Fructose has a more pronounced effect than sucrose, and a monosaccharide has a more obvious effect than polysaccharide [37], which is consistent with the results of other studies [38,39].…”

Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View

“…Furthermore, the consumption of fructose has significantly increased worldwide with the growth of processed foods using high fructose corn syrup [22]. In the liver, fructose metabolism is different from glucose metabolism and proceeds without regulation, thus providing excess acetyl units that promotes a hepatic prolipogenic state [23], with further ATP depletion, oxidative stress, n-3 LCPUFA depletion, and development of a proinflammatory state [24,25]. Moreover, derangements in liver iron and copper homeostasis are related to the development of NAFLD.…”