Interaction of the level of dietary fat and type of carbohydrate in the regulation of hepatic lipogenesis in the mouse

Abstract

We have studied hepatic and extrahepatic lipogenesis in mice fed diets containing 0, 5, 10, or 15% corn oil in which the carbohydrate was one of fructose, sucrose, glucose, or wheat starch. Meal-fed animals were trained to eat a quantity of food such that at a given level of fat ail animals consumed the same amount of carbohydrate. Fatty acids synthesis in vivo, acetyl CoA carboxylase, fatty acid synthetase, ATP citrate lyase, glucose-6-phosphate dehydrogenase, and malic enzyme were determined. At 0 and 5% corn oil the values generally decreased in the order fructose > sucrose > glucose > wheat starch. At 10 and 15% corn oil differences due to the type of carbohydrate were less pronounced. The effect of dietary carbohydrate on glucokinase activity followed the reverse pattern with the values decreasing in the order wheat starch > glucose > sucrose > fructose. The results obtained demonstrate that hepatic lipogenesis was increased in mice consuming fructose or sucrose independent of carbohydrate intake or the level of dietary fat. However, total capacity for lipogenesis was greater in glucose-fed mice than those consuming wheat starch, fructose, or sucrose. Regardless of the carbohydrate in the diet, as dietary fat increased all the lipogenic parameters measured declined.Increasing corn oil from 0 to 15% caused a greater change in lipogenic capacity than the change due to the various carbohydrates. The percentage of total synthesis which occurred in liver was greater in mice fed fructose or sucrose. This increased contribution by the liver was unaltered by dietary fat which may contribute to the hypertriglyceridemia in such animals. Compared with diets based on glucose or wheat starch, diets based on fructose or sucrose do not cause increased lipogenesis in meal-fed mice if the diets contain more than 30 calorie percent fat. Our results suggest that when diets contain fat a a level similar to that in North American diets, the effects of the type of dietary carbohydrate on lipogenesis are minimal.

Fructose impairs glucose-induced hepatic triglyceride synthesis

“…The athymic Nu/Nu mouse represents a model of non obese non-immune non-insulin-dependent diabetes [43,44] and has been used to delineate immune-mediated pancreatic islet effects in insulin-dependent diabetes mellitus [45,46]. Our studies demonstrate that unlike the C57Bl/6 mouse, increased CHO feeding to Nu/Nu mice results in development of a metabolic syndrome phenotype with modestly impaired peripheral glucose disposal.…”

Comparative Effects of Fructose and Glucose on Lipogenic Gene Expression and Intermediary Metabolism in HepG2 Liver Cells

“…Questions that have remained unanswered, however, are whether or not acute or chronic hepatic fructose exposure can predispose toward a lipogenic state through activation of lipogenic enzyme expression and if so, what are the metabolite signals involved? It is well-documented in animal models that the consumption of large amounts of fructose is associated with increases in liver expression of lipogenic FAS and ACC-1 enzymes [3], [15], [18], [19]. Should this take place in human liver upon chronic excessive dietary fructose intake, it would have important implications for lipid homeostasis since elevated DNL in the basal state and following sugar intake would be expected as a result of increased lipogenic enzyme capacity.…”

“…It is well documented that feeding of high sucrose or high fructose diets (or drinking high levels of these sugars) to mice and rats increases the mRNA levels and enzymatic activities of the key lipogenic enzymes fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC-1, or ACCα) in the liver [13], [14], [15], [16], [17], [18]. Several investigators have found that fructose feeding in rodents results in increased FAS activity and hepatic triglyceride content when compared with isocaloric diets of glucose, sucrose, or starch [14], [19], [20]. High fructose feeding to rodents has also been shown to raise the hepatic mRNA levels of transcription factors, including sterol regulatory element binding protein-1 (SREBP-1) and carbohydrate response element binding protein (ChREBP), involved in the regulation of genes encoding glycolytic and lipogenic enzymes [18], [21], [22].…”

Diabetes and hypertriglyceridemia modify the mode of acetaminophen-induced hepatotoxicity and nephrotoxicity in rats and mice

“…This suggests that enhancement of fructose metabolism in conjugation with overproduction of triglyceride in both liver and kidney is responsible -ty in fructose-induced hypertriglyceridemic rats. The contrast in triglyceride production between fructose and glulipogenic substrates available in the liver (Herzberg and Rogerson, 1982;Spence and Pitot, 1982). Neither hyperglycemia nor hyperinsulimemia can account for changes in APAP-toxicity in diabetic animal models since both fructose and glucose pretreatments produce both conditions (Kazumi et al, 1986), but only fructose pretreatment produces hypertriglyceridemia and changes in APAP-toxicity (Ishida et al, 1995).…”