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

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.

High fructose corn syrup supplementation progressively increased serum adenosine and inosine: Inosine raising blood pressure and heart rate in rats

High fructose corn syrup (HFCS) over-consumption underlies the obesity worldwide epidemics. Hepatic fructose metabolism includes fructolysis, lipogenesis, and purines degradation to uric acid. The aim of this study was to evaluate HFCS long-term effects on serum and hepatic adenosine (Ado) and inosine (Ino), as well as in vivo Ino effects on cardiovascular function. Fed male Wistar rats were subjected to 30% HFCS-enriched drinking water for five months (n = 15); every month, nucleosides were determined in serum and in isolated liver perfusate. Three months-old male naive Wistar rats were pithed and cannulated to record blood pressure and heart rate after Ino administration (n = 3). Rats consuming HFCS increased both Ado and Ino progressively in serum and livers’ perfusate; Ino increased cardiovascular function. The progressive Ado and Ino hepatic release by fructose-enriched diet suggests their contribution to raise glycemia through their gluconeogenic activation, and a higher serum Ino concentration might be related to increase in arterial blood pressure.