Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue

• Published in: Journal of Immunology Vol. 179; no. 7; pp. 4829 - 4839
• Main Authors: Wu, Dayong, Ren, Zhihong, Pae, Munkyong, Guo, Weimin, Cui, Xuelin, Merrill, Alfred H, Meydani, Simin Nikbin
• Format: Journal Article
• Language: English
• Published: England Am Assoc Immnol 01.10.2007
• Subjects: Adipose Tissue - cytology; Adipose Tissue - metabolism; Aging - physiology; Animals; Cells, Cultured; Ceramides - metabolism; Inflammation Mediators - metabolism; Leukocyte Count; Macrophages - cytology; Mice; NF-kappa B - metabolism; RNA, Messenger - genetics; Up-Regulation - genetics
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.7.4829

Obesity is a leading risk factor for type 2 diabetes (T2D). Aging is associated with an increase in T2D incidence, which is not totally explained by the much lower prevalence of obesity in the elderly. Low-grade inflammation in adipose tissue (AT) contributes to insulin resistance and T2D. Thus, we determined whether inflammatory responses are up-regulated with age in AT. The results showed that visceral AT from old C57BL mice had significantly higher mRNA expression of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and COX-2 and lower expression of anti-inflammatory PPAR-γ than those of young mice. We further showed that adipocytes (AD) and not stromal vascular cells including macrophages (Mφ) were the cells responsible for this higher inflammatory state of the aged AT, suggesting that the age-associated increase in AT inflammation is distinguished from that seen in obesity, in which Mφ are the main contributors. However, peritoneal Mφ of either age (young or old) produced more TNF-α and IL-6 after incubation in old AD-conditioned medium compared with young AD-conditioned medium. This suggests that in addition to producing more inflammatory cytokines, AD from old mice induce a higher inflammatory response in other cells. Sphingolipid ceramide was higher in old compared with young AD. Reducing ceramide levels or inhibiting NF-κB activation decreased cytokine production, whereas the addition of ceramide increased cytokine production in young AD to a level comparable to that seen in old AD, suggesting that ceramide-induced activation of NF-κB plays a key role in AT inflammation.