ChREBP/ ChREBP-beta expression mediates the paradoxical effect of fructose on body weight of fructose-fed rats by brown adipose tissue activation

Abstract

Introduction: Western diet fructose content is a neglected nutrition component, with significant devastating metabolic effects like metabolic syndrome (MeS) and obesity. The data suggest that Food-induced thermogenesis is a contributing factor for regulating body weight. Carbohydrate Responsive Element Binding Protein-beta (ChREBPβ) is recognized now as the regulator of fructose metabolism. Brown adipose tissue (AT) which plays essential role as a thermoregulatory organ, is recognized now also as an endocrine tissue that participates in glucose and lipids metabolism. ChREBP expression is associated with activating of BAT and improve metabolic status. On the other hand, increased ChREBPβ seems to have a deleterious metabolic effect on brown AT. Methods: Sprague-Dawley male rats, 8 weeks old were fed High Fructose Diet (HFRD) or match regular chow for 6 weeks (n=8). Body weight (BW) and precise food intake were measured weekly. Brown (peri-aortic and interscapular, PA and IS respectively) and white (mesenteric) AT were collected for further molecular studies. Results: HFrD fed rats gain significantly less weight than the control group (from 236±2 to 397±8 vs. 233±2 to 430±9 gr. P<0.05) despite eating an equal food amount (28±1vs.29±1.5 g/rat/week). The expression of uncoupling 1 (UCP1) mRNA, a BAT activation marker, was significantly higher in BAT than in WAT. Fructose consumption increased UCP1 BAT expression compared to regular chow. However, the expression of ChREBP and ChREBPβ in BAT was significantly lower in HFrD fed rats. Conclusions: In the HFrD rat model of MeS, fructose consumption leads to lesser weight gain for the same caloric intake. This BW difference is accompanied by the activation of BAT in the HFrD group. This paradoxical effect may be regulated by decreased ChREBP/ChREBPβ expression in response to fructose. No disclosure This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.