Zhang Xiaofang, Wang Qingxuan, Wang Yaru, Ma Chen, Zhao Qing, Yin Hongyan, Li Long, Wang Dongmei, Huang Yinxiang, Zhao Yan, Shi Xiulin, Li Xuejun, Huang Caoxin
Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China.
Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China; Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China.
Int Immunopharmacol. 2024 May 10;132:111906. doi: 10.1016/j.intimp.2024.111906. Epub 2024 Apr 8.
Age-related visceral obesity could contribute to the development of cardiometabolic complications. The pathogenesis of visceral fat mass accumulation during the aging process remains complex and largely unknown. Interleukin-6 (IL-6) has emerged as one of the prominent inflammaging markers which are elevated in circulation during aging. However, the precise role of IL-6 in regulating age-related visceral adipose tissue accumulation remains uncertain.
A cross-sectional study including 77 older adults (≥65 years of age) was initially conducted. There was a significant positive association between serum IL-6 levels and visceral fat mass. We subsequently validated a modest but significant elevation in serum IL-6 levels in aged mice. Furthermore, we demonstrated that compared to wildtype control, IL-6 deficiency (IL-6 KO) significantly attenuated the accumulation of visceral adipose tissue during aging. Further metabolic characterization suggested that IL-6 deficiency resulted in improved lipid metabolism parameters and energy expenditure in aged mice. Moreover, histological examinations of adipose depots revealed that the absence of IL-6 ameliorated adipocyte hypertrophy in visceral adipose tissue of aged mice. Mechanically, the ablation of IL-6 could promote the PKA-mediated lipolysis and consequently mitigate lipid accumulation in adipose tissue in aged mice.
Our findings identify a detrimental role of IL-6 during the aging process by promoting visceral adipose tissue accumulation through inhibition of lipolysis. Therefore, strategies aimed at preventing or reducing IL-6 levels may potentially ameliorate age-related obesity and improve metabolism during aging.
与年龄相关的内脏肥胖可能导致心脏代谢并发症的发生。衰老过程中内脏脂肪量积累的发病机制仍然复杂且很大程度上未知。白细胞介素-6（IL-6）已成为衰老过程中循环中升高的主要炎症衰老标志物之一。然而，IL-6在调节与年龄相关的内脏脂肪组织积累中的精确作用仍不确定。
最初进行了一项横断面研究，纳入77名老年人（≥65岁）。血清IL-6水平与内脏脂肪量之间存在显著正相关。随后，我们验证了老年小鼠血清IL-6水平有适度但显著的升高。此外，我们证明，与野生型对照相比，IL-6缺乏（IL-6基因敲除）显著减弱了衰老过程中内脏脂肪组织的积累。进一步的代谢特征表明，IL-6缺乏导致老年小鼠脂质代谢参数改善和能量消耗增加。此外，对脂肪库的组织学检查显示，缺乏IL-6可改善老年小鼠内脏脂肪组织中的脂肪细胞肥大。从机制上讲，IL-6的缺失可促进蛋白激酶A介导的脂肪分解，从而减轻老年小鼠脂肪组织中的脂质积累。
我们的研究结果确定了IL-6在衰老过程中的有害作用，即通过抑制脂肪分解促进内脏脂肪组织积累。因此，旨在预防或降低IL-6水平的策略可能会改善与年龄相关的肥胖，并改善衰老过程中的代谢。
