Vatner Stephen F, Zhang Jie, Oydanich Marko, Vatner Dorothy E
Department of Cell Biology and Molecular Medicine, Rutgers, New Jersey Medical School, Newark, NJ 07103, USA.
Int J Mol Sci. 2025 Apr 26;26(9):4113. doi: 10.3390/ijms26094113.
The Regulator of G Protein Signaling 14 () knockout (KO) mouse is a model of healthful longevity, i.e., its lifespan is prolonged and demonstrates enhanced exercise performance and protection against heart disease and hypertension. In this investigation, we found the RGS14 KO mouse is also protected against obesity and glucose intolerance by promoting a low white adipose tissue (WAT) phenotype with increased brown adipose tissue (BAT). This was confirmed by lower body weight, lower white adipocyte size, increased metabolism and improved glucose tolerance and insulin sensitivity. Upon examination of the white adipose tissue, RGS14 KO exhibited increased expression of "beiging" genes as well as significant increase in Uncoupling protein-1 (UCP-1) expression. The mechanism behind this protection was due to its unique brown adipose tissue. This was determined by BAT transplantation, which led to a reversal of phenotype, such that RGS14 BAT recipients developed protection similar to intact RGS14 KO mice, and the RGS14 KO BAT donors lost their protection. Thus, two novel mechanisms mediating obesity and glucose intolerance were found, i.e., inhibition of and its BAT.
G蛋白信号调节因子14（RGS14）基因敲除（KO）小鼠是健康长寿的一种模型，即其寿命延长，运动能力增强，对心脏病和高血压具有保护作用。在本研究中，我们发现RGS14基因敲除小鼠还可通过促进具有棕色脂肪组织（BAT）增加的低白色脂肪组织（WAT）表型来预防肥胖和葡萄糖不耐受。这通过较低的体重、较小的白色脂肪细胞大小、增加的新陈代谢以及改善的葡萄糖耐量和胰岛素敏感性得到证实。在检查白色脂肪组织时，RGS14基因敲除小鼠表现出“米色化”基因表达增加以及解偶联蛋白-1（UCP-1）表达显著增加。这种保护作用背后的机制归因于其独特的棕色脂肪组织。这通过BAT移植得以确定，移植导致表型逆转，使得RGS14 BAT受体产生了与完整的RGS14基因敲除小鼠相似的保护作用，而RGS14基因敲除BAT供体失去了其保护作用。因此，发现了两种介导肥胖和葡萄糖不耐受的新机制，即RGS14的抑制作用及其BAT。
