Shapira Shiran, Kazanov Dina, Dankner Rachel, Fishman Sigal, Stern Naftali, Arber Nadir
The Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.
Department of Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
J Pers Med. 2021 Jan 15;11(1):50. doi: 10.3390/jpm11010050.
The heat-stable HSA/CD24 gene encodes a protein that shows high expression levels in adipocyte precursor cells but low levels in terminally differentiated adipocytes. Its high expression in many types of human cancer suggests an association between cancer, diabetes, and obesity, which is currently unclear. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) is a regulator of adipogenesis that plays a role in insulin sensitivity, lipid metabolism, and adipokine expression in adipocytes.
To assess gender-dependent changes in CD24 KO and its association with PPARγ expression.
WT and CD24 KO mice were monitored from birth up to 12 months, and various physiological and molecular characteristics were analysed. Mean body weight and adipose mass were higher in KO mice than in WT mice. Male, but not female, KO mice showed increased insulin sensitivity, glucose uptake, adipocyte size, and PPARγ expression than WT mice. In addition, enteric bacterial populations, assessed through high-throughput sequencing of stool 16S rRNA genes, were significantly different between male KO and WT mice.
CD24 may negatively regulate PPARγ expression in male mice. Furthermore, the association between the CD24 and insulin sensitivity suggests a possible mechanism for diabetes as a cancer risk factor. Finally, CD24 KO male mice may serve as a model of obesity and insulin hyper-sensitivity.
热稳定的HSA/CD24基因编码一种在脂肪细胞前体细胞中高表达而在终末分化的脂肪细胞中低表达的蛋白质。其在多种人类癌症中的高表达提示癌症、糖尿病和肥胖之间存在关联，目前尚不清楚。此外，过氧化物酶体增殖物激活受体γ（PPARγ）是脂肪生成的调节因子，在脂肪细胞的胰岛素敏感性、脂质代谢和脂肪因子表达中起作用。
评估CD24基因敲除（KO）的性别依赖性变化及其与PPARγ表达的关联。
对野生型（WT）和CD24 KO小鼠从出生到12个月进行监测，并分析各种生理和分子特征。KO小鼠的平均体重和脂肪量高于WT小鼠。雄性而非雌性KO小鼠比WT小鼠表现出更高的胰岛素敏感性、葡萄糖摄取、脂肪细胞大小和PPARγ表达。此外，通过粪便16S rRNA基因高通量测序评估的肠道细菌种群在雄性KO和WT小鼠之间存在显著差异。
CD24可能对雄性小鼠的PPARγ表达起负调节作用。此外，CD24与胰岛素敏感性之间的关联提示糖尿病作为癌症风险因素的一种可能机制。最后，CD24 KO雄性小鼠可作为肥胖和胰岛素高敏性的模型。
