Location: Obesity and Metabolism ResearchTitle: Obesogenic and diabetic effects of CD44 in mice are sexually dimorphic and dependent on genetic background
|VERHAGUE, MELISSA - University Of North Carolina|
|ALBRIGHT, JODY - University Of North Carolina|
|BARRON, KERI - University Of North Carolina|
|KIM, MYUNGSUK - University Of California, Davis|
Submitted to: Biology of Sex Differences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/29/2022
Publication Date: 4/11/2022
Citation: VerHague, M., Albright, J., Barron, K., Kim, M., Bennett, B.J. 2022. Obesogenic and diabetic effects of CD44 in mice are sexually dimorphic and dependent on genetic background. Biology of Sex Differences. 13. Article 14. https://doi.org/10.1186/s13293-022-00426-2.
Interpretive Summary: Numerous studies have linked an inflammatory gene, CD44, with obesity and diabetes. Our current study first investigates the relationship between CD44 and the severity of adiposity in human subjects and then tests this relationship in 2 different genetically defined mouse strains. In humans, we found that CD44 levels increase in the blood as the degree of body fatness increases. The subsequent studies in mice genetically engineered to not express CD44 confirmed these results in humans. We used 2 different strains of mice to identify that the obesity effects of CD44 are independent of a well described inflammatory pathways suggesting alternative regulation of obesity.
Technical Abstract: CD44 is a candidate gene for obesity and diabetes development and may be a critical mediator of a systemic inflammation associated with obesity and diabetes. We investigated the relationship of CD44 with obesity in overweight and obese humans. Subsequent studies utilized CD44 deficient mice challenged with a high fat diet. Our results in humans indicated that circulating CD44 was higher in obese compared to overweight participants and was related to severity of obesity as determined by DEXA. In mice fed a diet high in fat and sucrose for 7 weeks, fat mass accumulation is reduced in CD44-/- mice bred onto both a C57BL/6J and the TLR4 deficient strain C3H/HeJ background, relative to wild-type mice. Reduced fat mass could not be attributed to lower food intake or an increase in energy expenditure as measured by indirect calorimetry. However, we observed a 40-60% decreased mRNA expression of the inflammation markers, F4/80, CD11b, TNF-alpha and CD14, in adipose tissue of C57BL/6J but not C3H/HeJ, perhaps indicating that alternative factors may be affected adiposity in this model. Measures of hepato-steatosis and insulin sensitivity were improved in CD44-/- mice on a C57BL/6J but not in the C3H/HeJ mice. These results were highly sexually dimorphic as there were no detectable effects of CD44 inactivation in female mice on a C57BL/6J or C3H/HeJ background.