Aging up-regulates expression of inflammatory mediators in mouse adipose tissue.
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-1beta, IL-6, TNF-alpha, and COX-2 and lower expression of anti-inflammatory PPAR-gamma than those of young mice. We further showed that adipocytes (AD) and not stromal vascular cells including macrophages (Mphi) 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 Mphi are the main contributors. However, peritoneal Mphi of either age (young or old) produced more TNF-alpha 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-kappaB 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-kappaB plays a key role in AT inflammation.
Wu
Dayong
D
Nutritional Immunology Laboratory, Jean Mayer Unites States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. dayong.wu@tufts.edu
Ren
Zhihong
Z
Pae
Munkyong
M
Guo
Weimin
W
Cui
Xuelin
X
Merrill
Alfred H
AH
Meydani
Simin Nikbin
SN
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
D002518:Ceramides; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger