Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver fatty acid-binding protein (L-Fabp) regulates murine hepatic fatty acid trafficking in response to fasting. In this study, we show that L-Fabp(-/-) mice fed a high-fat Western diet for up to 18 weeks are less obese and accumulate less hepatic triglyceride than C57BL/6J controls. Paradoxically, both control and L-Fabp(-/-) mice manifested comparable glucose intolerance and insulin resistance when fed a Western diet. Protection against obesity in Western diet-fed L-Fabp(-/-) mice was not due to discernable changes in food intake, fat malabsorption, or heat production, although intestinal lipid secretion kinetics were significantly slower in both chow-fed and Western diet-fed L-Fabp(-/-) mice. By contrast, there was a significant increase in the respiratory exchange ratio in L-Fabp(-/-) mice, suggesting a shift in energy substrate use from fat to carbohydrate, findings supported by an approximately threefold increase in serum lactate. Microarray analysis revealed increased expression of genes involved in lipid synthesis (fatty acid synthase, squalene epoxidase, hydroxy-methylglutaryl coenzyme A reductase), while genes involved in glycolysis (glucokinase and glycerol kinase) were decreased in L-Fabp(-/-) mice. Fatty acid synthase expression was also increased in the skeletal muscle of L-Fabp(-/-) mice. In conclusion, L-Fabp may function as a metabolic sensor in regulating lipid homeostasis. We suggest that L-Fabp(-/-) mice are protected against Western diet-induced obesity and hepatic steatosis through a series of adaptations in both hepatic and extrahepatic energy substrate use. (HEPATOLOGY 2006;44:1191-1205.).
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PMID:Protection against Western diet-induced obesity and hepatic steatosis in liver fatty acid-binding protein knockout mice. 1705 18

Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important for the treatment of metabolic syndrome and fructose malabsorption. Carbohydrate response element binding protein (ChREBP) is a glucose-activated transcription factor that controls approximately 50% of de novo lipogenesis in the liver. ChREBP target genes are involved in glycolysis (Glut2, liver pyruvate kinase), fructolysis (Glut5, ketohexokinase), and lipogenesis (acetyl CoA carboxylase, fatty acid synthase). ChREBP gene deletion protects against high sucrose diet-induced and leptin-deficient obesity, because Chrebp-/- mice cannot consume fructose or sucrose. Moreover, ChREBP contributes to some of the physiological effects of fructose on sweet taste preference and glucose production through regulation of ChREBP target genes, such as fibroblast growth factor-21 and glucose-6-phosphatase catalytic subunits. Thus, ChREBP might play roles in fructose metabolism. Restriction of excess fructose intake will be beneficial for preventing not only metabolic syndrome but also irritable bowl syndrome.
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PMID:The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism. 2824 31