Metabolic effects of oral fructose in the liver of fasted rats

Abstract

Twenty-four-hour-fasted rats were given fructose (4 g/kg) by gavage. Fructose absorption and the portal vein, aorta, and hepatic vein plasma fructose, glucose, lactate, and insulin concentrations as well as liver fructose and fructose 1-P, glucose, glucose 6-P, UDPglucose, lactate, pyruvate, ATP, ADP, AMP, inorganic phosphate (Pi), cAMP, and Mg2+, and glycogen synthase I and phosphorylase alpha were measured at 10, 20, 30, 40, 60 and 120 min after gavage. Liver and muscle glycogen and serum uric acid and triglycerides also were measured. Fifty-nine percent of the fructose was absorbed in 2 h. There were modest increases in plasma and hepatic fructose, glucose, and lactate and in plasma insulin. Concentrations in the portal vein, aorta, and hepatic vein plasma indicate rapid removal of fructose and lactate by the liver and a modest increase in production of glucose. The source of the increase in plasma lactate is uncertain. Hepatic glucose 6-P increased twofold; UDPglucose rose transiently and then decreased below the control level. Fructose 1-P increased linearly to a concentration of 3.3 mumol/g wet wt by 120 min. There was no change in ATP, ADP, AMP, cAMP, Pi, or Mg2+. Serum triglycerides and uric acid were unchanged. Glycogen synthase was activated by 20 min without a change in phosphorylase alpha. This occurred with a fructose dose that did not significantly increase either the liver glucose or fructose concentrations. Liver glycogen increased linearly after 20 min, and glycogen storage was equal in liver (38.4%) and muscle (36.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential Intrahepatic Metabolic Effects of Enteric Galactose Alimentation in Newborn Rats

“…In the present neonatal investigation the most striking and perhaps clinically significant observation was the increase of hepatic galactose-1-phosphate concentrations after galactose alimentation. Similar observations of an increase of fructose-lphosphate levels were noted in adult rats fed fructose (21). Although the amount of galactose administered was a physiologic quantity, it may be concerning that galactose-1-phosphate levels increased after galactose alimentation and that this increment persisted after blood galactose levels had returned to normal.…”

“…The alteration of glucosed-phosphate suggests that both carbohydrates enriched this intermediate pool (19,21). Glucose would do this directly after phosphorylation by glucokinase (7).…”

Fructose metabolism and metabolic disease

“…Lastly, F1P also allosterically activates pyruvate kinase, the terminal step in glycolysis, contributing to increased circulating lactate levels following fructose ingestion (69). In rodent liver, hepatic F1P levels increase 10-fold to approximately 1 mM within 10 minutes after fructose ingestion and remain elevated for several hours (70). F1P concentrations of only approximately 200 μM are sufficient to alleviate the inhibitory effect of GCKR on GCK (71).…”

ChREBP regulates fructose-induced glucose production independently of insulin signaling

“…We administered fructose to mice to model the effects of increased hepatic CHO metabolites, since fructose is preferentially metabolized in the liver (26) and can rapidly increase hepatic CHO metabolite levels (27). Also, increased fructose consumption as a component of sucrose or high-fructose corn syrup is increasingly associated with cardiometabolic disease in humans (28).…”