Preprint Article Version 1 This version not peer reviewed

ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption

Version 1 : Received: 31 January 2018 / Approved: 1 February 2018 / Online: 1 February 2018 (05:09:54 CET)

How to cite: Kato, T.; Iizuka, K.; Takao, K.; Horikawa, Y.; Kitamura, T.; Takeda, J. ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption. Preprints 2018, 2018020005 (doi: 10.20944/preprints201802.0005.v1). Kato, T.; Iizuka, K.; Takao, K.; Horikawa, Y.; Kitamura, T.; Takeda, J. ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption. Preprints 2018, 2018020005 (doi: 10.20944/preprints201802.0005.v1).

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. 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.

Subject Areas

carbohydrate-responsive element-binding protein; ketohexokinase; fructose; glucose transporter 5; glucose transporter 2

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