Abstract
We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild-type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. A thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression.
Highlights
Excess intake of high sucrose and fructose diet were thought to be associated with the development of obesity, metabolic syndrome and diabetes [1,2]
Sucrose is a disaccharide composed of glucose and fructose, and is digested by intestinal sucrase-isomaltase (SI), which is inhibited by miglitol, an α-glucosidase inhibitor [5]
To clarify the intestinal sucrose and fructose metabolism, we focused on the phenotypes of high-sucrose diet-fed carbohydrate-responsive element-binding protein (ChREBP)-knockout (KO)
Summary
Excess intake of high sucrose and fructose diet were thought to be associated with the development of obesity, metabolic syndrome and diabetes [1,2]. For example, experiments feeding 70% fructose-containing water, supported this hypothesis [2]. Recent human epidemic data suggest that there is little association between metabolic syndrome and consumption of sucrose and fructose [3,4]. The mechanism of sucrose and fructose metabolism remains unclear. Sucrose is a disaccharide composed of glucose and fructose, and is digested by intestinal sucrase-isomaltase (SI), which is inhibited by miglitol, an α-glucosidase inhibitor [5]. Fructose is more potent and has higher capacity of protein glycation than glucose, and is more harmful than glucose [6]
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