Published on January 20, 2022–Updated on November 20, 2024
E. Recazens, G. Tavernier, J. Dufau, C. Bergoglio, F. Benhamed, S. Cassant-Sourdy, M-A. Marques, S. Caspar-Bauguil, A. Brion, L. Monbrun, R. Dentin, C. Ferrier, M. Leroux , P-D. Denechaud, C. Moro, J-P. Concordet, C. Postic, E. Mouisel, D. Langin (2022)
Abstract
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 two isoforms, ChREBPα, the full-length form which translocation into the nucleus is under the control of glucose and, ChREBPβ, a constitutively nuclear shorter form. ChREBPβ gene expression in white adipose tissue is strongly associated with insulin sensitivity. Here, we investigated the consequences of ChREBPβ deficiency on insulin action and energy balance. ChREBPβ-deficient male and female C57BL6/J and FVB/N mice were produced using CRISPR-Cas9-mediated gene editing. Unlike global ChREBP deficiency, lack of ChREBPβ showed modest effects on gene expression in adipose tissues and liver, with variations seen chiefly in brown adipose tissue. In mice fed chow and high fat diets, lack of ChREBPβ had moderate effects on body composition and insulin sensitivity. ChREBPβ deficiency did not prevent the whitening of brown adipose tissue reported in total ChREBP knock out mice at thermoneutrality. These findings reveal that ChREBPβ is dispensable for metabolic adaptations to nutritional and thermic challenges.
