The Roles of Carbohydrate Response Element Binding Protein in the Relationship between Carbohydrate Intake and Diseases.

Katsumi Iizuka

doi:10.3390/ijms222112058

Abstract

Carbohydrates are macronutrients that serve as energy sources. Many studies have shown that carbohydrate intake is nonlinearly associated with mortality. Moreover, high-fructose corn syrup (HFCS) consumption is positively associated with obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Accordingly, products with equal amounts of glucose and fructose have the worst effects on caloric intake, body weight gain, and glucose intolerance, suggesting that carbohydrate amount, kind, and form determine mortality. Understanding the role of carbohydrate response element binding protein (ChREBP) in glucose and lipid metabolism will be beneficial for elucidating the harmful effects of high-fructose corn syrup (HFCS), as this glucose-activated transcription factor regulates glycolytic and lipogenic gene expression. Glucose and fructose coordinately supply the metabolites necessary for ChREBP activation and de novo lipogenesis. Chrebp overexpression causes fatty liver and lower plasma glucose levels, and ChREBP deletion prevents obesity and fatty liver. Intestinal ChREBP regulates fructose absorption and catabolism, and adipose-specific Chrebp-knockout mice show insulin resistance. ChREBP also regulates the appetite for sweets by controlling fibroblast growth factor 21, which promotes energy expenditure. Thus, ChREBP partly mimics the effects of carbohydrate, especially HFCS. The relationship between carbohydrate intake and diseases partly resembles those between ChREBP activity and diseases.

Highlights

Most foods contain carbohydrates, which are macronutrients in the three groups monosaccharides, disaccharides, and polysaccharides [1]
Energy expenditure by fibroblast growth factor 21 (FGF21) was highest on the LP and HFCS diets, this diet evoked worse insulin resistance, glucose tolerance, and liver fat accumulation [38]. These changes observed with the LP and HFCS diets were more remarkable than those with the LP and sucrose diets [38]. These results suggested that high-fructose corn syrup is more harmful than sucrose and that glucose and fructose cooperatively promote the development of fatty liver
carbohydrate response element binding protein (ChREBP) overexpression consistently caused glucoseinduced islet proliferation [90]. These results suggest that ChREBP plays a role in glucoseinduced β cell proliferation [91,92,93]

Summary

Introduction

Most foods (e.g., bread, beans, rice, and milk) contain carbohydrates, which are macronutrients in the three groups monosaccharides, disaccharides, and polysaccharides [1]. Fructose is more rapidly converted into triglycerides and causes fatty liver and body weight gain [2]. Many studies have shown that the intake of fructose-containing sugar-sweetened beverages (SSBs) is positively associated with weight gain and the risk of T2DM [6,7]. Recent studies showed that smaller doses of fructose were metabolized into glucose and its metabolites in the intestine [32], whereas when administered at higher doses (1 g/kg body weight), fructose was delivered to the liver and metabolized into fatty acids and triglycerides [32]. In discussing the association between carbohydrates and mortality, we should not overeat carbohydrates, especially sugars

Dietary Fiber

The Regulation of ChREBP Activity

The Role of ChREBP in Several Tissues

Future Perspective

Findings

Conclusions