ChREBPβ is dispensable for the control of glucose homeostasis and energy balance

Impaired glucose metabolism is observed in obesity and type 2 diabetes. Glucose controls gene expression through the transcription factor ChREBP in liver and adipose tissues. Mlxipl encodes 2 isoforms: ChREBP alpha, the full-length form (translocation into the nucleus is under the control of glucose), and ChREBP beta, a constitutively nuclear shorter form. ChREBP beta gene expression in white adipose tissue is strongly associated with insulin sensitivity. Here, we investigated the consequences of ChREBP beta deficiency on insulin action and energy balance. ChREBP beta-deficient male and female C57BL6/J and FVB/N mice were produced using CRISPR/Cas9-mediated gene editing. Unlike global ChREBP deficiency, lack of ChREBP beta showed modest effects on gene expression in adipose tissues and the liver, with variations chiefly observed in brown adipose tissue. In mice fed chow and 2 types of high-fat diets, lack of ChREBP beta had moderate effects on body composition and insulin sensitivity. At thermoneutrality, ChREBP beta deficiency did not prevent the whitening of brown adipose tissue previously reported in total ChREBP-KO mice. These findings revealed that ChREBP beta is dispensable for metabolic adaptations to nutritional and thermic challenges.