Interleukin-6 promotes visceral adipose tissue accumulation during aging via inhibiting fat lipolysis

被引:1
作者
Zhang, Xiaofang [1 ]
Wang, Qingxuan [1 ]
Wang, Yaru [1 ]
Ma, Chen [1 ]
Zhao, Qing [1 ]
Yin, Hongyan [1 ]
Li, Long [1 ,2 ]
Wang, Dongmei [1 ,3 ]
Huang, Yinxiang [1 ]
Zhao, Yan [1 ]
Shi, Xiulin [1 ]
Li, Xuejun [1 ,4 ]
Huang, Caoxin [1 ,4 ]
机构
[1] Xiamen Univ, Affiliated Hosp 1, Xiamen Diabet Inst, Sch Med,Fujian Key Lab Translat Res Diabet,Dept En, Xiamen 361003, Peoples R China
[2] Ningbo Univ, Inst Drug Discovery Technol, Ningbo 315211, Peoples R China
[3] Xiamen Med Coll, Dept Publ Hlth & Med Technol, Xiamen 361023, Peoples R China
[4] Xiamen Univ, Affiliated Hosp 1, Xiamen Diabet Inst, Sch Med,Fujian Province Key Lab Translat Res Diabe, 55 Zhenhai Rd, Xiamen 361003, Peoples R China
基金
中国国家自然科学基金;
关键词
Aging; Visceral adipose; IL-6; Lipolysis; Obesity; NECROSIS-FACTOR-ALPHA; DIET-INDUCED OBESITY; INSULIN-RESISTANCE; PROINFLAMMATORY CYTOKINES; RHEUMATOID-ARTHRITIS; SIGNALING PATHWAY; DOUBLE-BLIND; BODY-WEIGHT; IN-VITRO; IL-6;
D O I
10.1016/j.intimp.2024.111906
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: 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. Results: 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. Conclusion: 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.
引用
收藏
页数:12
相关论文
共 107 条
[1]   Chemokine signaling via the CXCR2 receptor reinforces senescence [J].
Acosta, Juan C. ;
O'Loghlen, Ana ;
Banito, Ana ;
Guijarro, Maria V. ;
Augert, Arnaud ;
Raguz, Selina ;
Fumagalli, Marzia ;
Da Costa, Marco ;
Brown, Celia ;
Popov, Nikolay ;
Takatsu, Yoshihiro ;
Melamed, Jonathan ;
di Fagagna, Fabrizio d'Adda ;
Bernard, David ;
Hernando, Eva ;
Gil, Jesus .
CELL, 2008, 133 (06) :1006-1018
[2]   An Interleukin-6 Receptor Antibody Suppresses Atherosclerosis in Atherogenic Mice [J].
Akita, Koji ;
Isoda, Kikuo ;
Sato-Okabayashi, Yayoi ;
Kadoguchi, Tomoyasu ;
Kitamura, Kenichi ;
Ohtomo, Fumie ;
Shimada, Kazunori ;
Daida, Hiroyuki .
FRONTIERS IN CARDIOVASCULAR MEDICINE, 2017, 4
[3]   The Placental NLRP3 Inflammasome and Its Downstream Targets, Caspase-1 and Interleukin-6, Are Increased in Human Fetal Growth Restriction: Implications for Aberrant Inflammation-Induced Trophoblast Dysfunction [J].
Alfian, Irvan ;
Chakraborty, Amlan ;
Yong, Hannah E. J. ;
Saini, Sheetal ;
Lau, Ricky W. K. ;
Kalionis, Bill ;
Dimitriadis, Evdokia ;
Alfaidy, Nadia ;
Ricardo, Sharon D. ;
Samuel, Chrishan S. ;
Murthi, Padma .
CELLS, 2022, 11 (09)
[4]   Mitochondrial and metabolic dysfunction in ageing and age-related diseases [J].
Amorim, Joao A. ;
Coppotelli, Giuseppe ;
Rolo, Anabela P. ;
Palmeira, Carlos M. ;
Ross, Jaime M. ;
Sinclair, David A. .
NATURE REVIEWS ENDOCRINOLOGY, 2022, 18 (04) :243-258
[5]   Cellular Aging Contributes to Failure of Cold-Induced Beige Adipocyte Formation in Old Mice and Humans [J].
Berry, Daniel C. ;
Jiang, Yuwei ;
Arpke, Robert W. ;
Close, Elizabeth L. ;
Uchida, Aki ;
Reading, David ;
Berglund, Eric D. ;
Kyba, Michael ;
Graff, Jonathan M. .
CELL METABOLISM, 2017, 25 (01) :166-181
[6]   The nuclear factor-κB-interleukin-6 signalling pathway mediating vascular inflammation [J].
Brasier, Allan R. .
CARDIOVASCULAR RESEARCH, 2010, 86 (02) :211-218
[7]   IL-6 Regulates M2 Polarization and Local Proliferation of Adipose Tissue Macrophages in Obesity [J].
Braune, Julia ;
Weyer, Ulrike ;
Hobusch, Constance ;
Mauer, Jan ;
Bruening, Jens C. ;
Bechmann, Ingo ;
Gericke, Martin .
JOURNAL OF IMMUNOLOGY, 2017, 198 (07) :2927-2934
[8]   Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages [J].
Bu, Yun ;
Okunishi, Katsuhide ;
Yogosawa, Satomi ;
Mizuno, Kouichi ;
Irudayam, Maria Johnson ;
Brown, Chester W. ;
Izumi, Tetsuro .
DIABETES, 2018, 67 (09) :1761-1772
[9]   Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB [J].
Cai, DS ;
Yuan, MS ;
Frantz, DF ;
Melendez, PA ;
Hansen, L ;
Lee, J ;
Shoelson, SE .
NATURE MEDICINE, 2005, 11 (02) :183-190
[10]   Adipose tissue microenvironments during aging: Effects on stimulated lipolysis [J].
Camell, Christina D. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2022, 1867 (05)