VerHagye, Melissa Albright, Jody Barron, Keri Kim, Myung Suk Bennett, Brian 2024-01-12T03:31:44Z 2024-01-12T03:31:44Z 2022-04-13 2022-04 https://pubs.kist.re.kr/handle/201004/76757 Introduction 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. Methods We investigated the relationship of CD44 with obesity in CD44-deficient mice challenged with a high-fat diet. Results In mice fed a diet high in fat, cholesterol, and sucrose for 12 weeks fat mass accumulation was reduced in CD44-deficient mice bred onto both a C57BL/6J and the naturally TLR deficient C3H/HeJ background. 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% lower mRNA expression of the inflammation markers, F4/80, CD11b, TNF-alpha, and CD14, in adipose tissue of CD44-deficient mice on the C57BL/6J background but not the C3H/HeJ background, perhaps indicating that alternative factors may be affecting adiposity in this model. Measures of hepatic steatosis and insulin sensitivity were improved in CD44-deficient 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/6 J or C3H/HeJ background. Conclusion CD44 was associated with adiposity, liver fat, and glucose in male mice. However, the effects of CD44 on obesity may be independent of TLR4 signaling. English BioMed Central Obesogenic and diabetic effects of CD44 in mice are sexually dimorphic and dependent on genetic background Article 10.1186/s13293-022-00426-2 1 Biology of Sex Differences, v.13, no.1 Biology of Sex Differences 13 1 Y scie scopus 000783157600002 Endocrinology & Metabolism Genetics & Heredity Endocrinology & Metabolism Genetics & Heredity Article GENOME-WIDE ASSOCIATION BODY-MASS INDEX ADIPOSE-TISSUE HIGH-FAT INSULIN-RESISTANCE CRUCIAL ROLE OBESITY INFLAMMATION DIET EXPRESSION