| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Nutritional Immunology Laboratory, Jean Mayer Unites States Department of Agriculture Human Nutrition Research Center on Aging and
Department of Pathology, Sackler Graduate School of Biochemical Sciences, Tufts University, Boston, MA 02111;
National Institute of Communicable Disease Control and Prevention, China Center for Disease Control, Beijing, China; and
School of Biology and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332
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-1
, IL-6, TNF-
, and COX-2 and lower expression of anti-inflammatory PPAR-
than those of young mice. We further showed that adipocytes (AD) and not stromal vascular cells including macrophages (M
) 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 M are the main contributors. However, peritoneal M of either age (young or old) produced more TNF- 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-
B 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-B plays a key role in AT inflammation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institute of Aging Grant R01-AG009140-10A1, Office of Dietary Supplement, the U.S. Department of Agriculture, Agriculture Research Service under contract number 53-K06-01 (to S.N.M.), and the Obesity Seed Grant of Tufts University Vice Provost Office (to D.W.).
2 Address correspondence and reprint requests to Dr. Dayong Wu, Nutritional Immunology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111. E-mail address: dayong.wu{at}tufts.edu
3 Abbreviations used in this paper: T2D, type 2 diabetes; ACM, adipocyte-conditioned medium; C1P, ceramide-1-phosphate; COX, cyclooxygenase; GSH, glutathione; GSSG, glutathione disulfide; iNOS, inducible NO synthase; LDH, lactate dehydrogenase; Me-SM, 3-O-methylspingomyelin; M, macrophage; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium; nSMase, neutral sphingomyelinase; PPAR, peroxisome proliferator-activated receptor; RIA, radioimmunoassay; S1P, sphingosin-1-phosphate; SMase, sphingomyelinase; SPT, serine palmitoyltransferase; SVC, stromal vascular cell.
This article has been cited by other articles:
|
|
 |
|
  D. Wu and S. N. Meydani Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention J. Leukoc. Biol., October 1, 2008; 84(4): 900 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Csiszar, M. Wang, E. G. Lakatta, and Z. Ungvari Inflammation and endothelial dysfunction during aging: role of NF-{kappa}B J Appl Physiol, October 1, 2008; 105(4): 1333 - 1341. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
