Unaltered TNF-α production by macrophages and monocytes in diet-induced obesity in the rat

Journal of Inflammation

Margaret J Morris²  Gary P Anderson¹  Jessica E Jones¹  Steve Bozinovski¹  Elena Velkoska²  Sammy Bedoui² 

[1] Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Melbourne, 3010, Australia;Department of Pharmacology, The University of Melbourne, Melbourne, 3010, Australia

关键词: tumour necrosis factor;    obesity;    neuropeptide Y;    macrophage;    lipopolysaccharide;    leptin;    innate immunity;   

Others  :  826787
DOI  :  10.1186/1476-9255-2-2

 received in 2004-12-16, accepted in 2005-03-21,  发布年份 2005

【 摘 要 】

Background

Recent findings have established an association between obesity and immune dysfunction. However, most of the studies investigating the effects of obesity on immune function have been carried out in genetically obese rodent models. Since human obesity is mostly due to intake of a high fat diet and decreased energy expenditure, we asked whether immunological defects also occur in diet-induced obesity. Specifically, we focused on the function of monocytes and macrophages, as these cells are thought to be involved in the low-grade inflammation present in obesity.

Methods

Male Sprague-Dawley rats were fed a high-fat or a standard chow diet for either 2 or 10 weeks. At the end of the intervention period animals were anaesthetised, blood collected for determination of plasma mediator concentrations and lipopolysaccharide (LPS) stimulated production of TNF-α by monocytes. LPS stimulated production of TNF-α in alveolar macrophages was also determined.

Results

High-fat feeding for either 2 or 10 weeks resulted in significant increases in fat mass and serum leptin. Although increased serum leptin has previously been linked to modulation of innate immunity, we found no significant difference in the LPS stimulated production of TNF-α by either blood monocytes or alveolar macrophages between the dietary groups. Furthermore, we failed to find a significant increase in circulating TNF-α concentrations in obese animals, as reported for genetically obese animals.

Conclusion

Our data suggest that defects in innate immune function observed in genetically obese animals are not mimicked by dietary obesity, and may more likely reflect the gross abnormality in leptin function of these models. Further work is required delineate the effects of dietary obesity on inflammatory state and immune function.

【 授权许可】

   
2005 Bedoui et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Jeanrenaud B, Rohner-Jeanrenaud F: Effects of neuropeptides and leptin on nutrient partitioning: dysregulations in obesity. Annu Rev Med 2001, 52:339-351.
• [2]Marti A, Marcos A, Martinez JA: Obesity and immune function relationships. Obes Rev 2001, 2:131-140.
• [3]Dandona P, Aljada A, Bandypadhyay A: Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 2004, 25:4-7.
• [4]Stallone D: The influence of obesity and its treatment on the immune system. Nutr Rev 1994, 52:37-50.
• [5]Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM: Leptin regulates proinflammatory immune responses. FASEB J 1998, 12:57-65.
• [6]Faggioni R, Fantuzzi G, Gabay C, Moser A, Dinarello CA, Feingold KR, Grunfeld C: Leptin deficiency enhances sensitivity to endotoxin-induced lethality. Am J Physiol 1999, 276:R136-R142.
• [7]O'Rahilly S: Leptin: defining its role in humans by the clinical study of genetic disorders. Nutr Rev 2002, 60:30-34.
• [8]Faggioni R, Feingold KR, Grunfeld C: Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 2003, 15:2565-2571.
• [9]Wellen EW, Hotamisligil GS: Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003, 112:1785-1788.
• [10]Bozinovski S, Jones JE, Vlahos R, Hamilton JA, Anderson GP: Granulocyte/macrophage-colony-stimulating factor (GM-CSF) regulates lung innate immunity to lipopolysaccharide through Akt/Erk activation of NFkappa B and AP-1 in vivo. J Biol Chem 2002, 277:42808-42814.
• [11]Bedoui S, Miyake S, Lin Y, Miyamoto K, Oki S, Kawamura N, Beck-Sickinger S, von Hörsten S, Yamamura T: Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis: NPY1 receptor-specific inhibition of autoreactive Th1 responses in vivo. J Immunol 2003, 171:3451-3458.
• [12]Bedoui S, Pabst R, von Hörsten S: NPY and immune functions: implications for health and disease. In Handbook of Pharmacology: NPY and related peptides. Edited by Michael, MC. Netherlands: Springer Press; 2004:409-446.
• [13]Morris MJ, Russel AE, Kapoor V, Cain MD, Elliott JM, West MJ, Wing LM, Chalmers JP: Increases in plasma neuropeptide Y concentrations during sympathetic activation in man. J Auton Nerv Syst 1986, 17:143-149.
• [14]Morris MJ, Kapoor V, Chalmers JP: Plasma neuropeptide Y concentration is increased after hemorrhage in conscious rats: relative contributions of sympathetic nerves and the adrenal medulla. J Cardiovasc Pharmacol 1987, 9:541-545.
• [15]Ikeda A, Chang Kt, Matsumoto Y, Furuhata Y, Nishihara M, Sasaki F, Takahashi M: Obesity and insulin resistance in human growth hormone transgenic rats. Endocrinology 1998, 139:3057-3063.
• [16]Hansen MJ, Ball MJ, Morris MJ: Enhanced inhibitory feeding response to alpha-melanocyte stimulating hormone in the diet-induced obese rat. Brain Res 2001, 892:130-137.
• [17]Hansen MJ, Jovanovska V, Morris MJ: Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high- fat feeding in the rat. J Neurochem 2004, 88:909-916.
• [18]Plotkin BJ, Paulson D, Chelich A, Jurak D, Cole J, Ksimos J, Burdick JR, Casteel N: Immune responsiveness in a rat model for type II diabetes (Zucker rat, fa/fa): susceptibility to Candida albicans infection and leucocyte function. J Med Microbiol 1996, 44:277-283.
• [19]Lamas O, Martinez JA, Marti A: Energy restriction restores the impaired immune response in overweight (cafeteria) rats. J Nutr Biochem 2004, 15:418-25.
• [20]Mito N, Kitada C, Hosoda T, Sato K: Effect of diet-induced obesity on ovalbumin-specific immune response in a murine asthma model. Metabolism 2002, 51:1241-6.
• [21]Zarkesh-Esfahani H, Pockley AG, Wu Z, Hellewell PG, Weetman AP, Ross RJ: Leptin indirectly activates human neutrophils via induction of TNF-alpha. J Immunol 2004, 172:1809-14.
• [22]Inui A: Obesity – a chronic health problem in cloned mice? Trends Pharmacol Sci 2003, 24:77-80.
• [23]Bochkov V, Kadl A, Huber J, Gruber F, Binder BR, Leitinger N: Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature 2002, 419:77-81.
• [24]Grimble RF: Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002, 5:551-559.
• [25]Black P: The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun 2003, 17:350-364.
• [26]Hukshorn CJ, Lindeman JH, Toet KH, Saris WH, Eilers PH, Westerterp-Plantenga MS, Kooistra T: Leptin and the proinflammatory state associated with human obesity. J Clin Endocrinol Metab 2004, 89:1773-1778.
• [27]Chan JC, Cheung JC, Stehouwer CD, Emeis JJ, Tong PC, Ko GT, Yudkin JS: The central roles of obesity-associated dyslipidaemia, endothelial activation and cytokines in the Metabolic Syndrome – an analysis by structural equation modelling. Int J Obes Relat Metab Disord 2002, 26:994-1008.
• [28]Warne J: Tumour necrosis factor alpha: a key regulator of adipose tissue mass. J Endocrinol 2003, 177:351-355.
• [29]van Dielen FM, van't Veer C, Schols AM, Soeters PB, Buurman WA, Greve JW: Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. Int J Obes Relat Metab Disord 2001, 25:1759-1766.
• [30]Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU, Eldrup E, Dela F, Pedersen BK: Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev 2003, 124:495-502.
• [31]Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H: Chronic inflammation in fat plays a critical role in the development of obesity-related insulin resistance. J Clin Invest 2003, 112:1821-1830.
• [32]Tappy L, Girardet K, Schwaller N, Vollenweider L, Jequier E, Nicod P, Scherrer U: Metabolic effects of an increase of sympathetic activity in healthy humans. Int J Obes Relat Metab Disord 1995, 16:419-422.
• [33]Kaufman LN, Young JB, Landsberg L: Effect of protein on sympathetic nervous system activity in the rat. Evidence for nutrient-specific responses. J Clin Invest 1986, 77:551-558.
• [34]Rumantir MS, Vaz M, Jennings GL, Collier G, Kaye DM, Seals DR, Wiesner GH, Brunner-La Rocca HP, Esler MD: Neural mechanisms in human obesity-related hypertension. J Hypertens 1999, 17:1125-1133.
• [35]Bray G, Bouchard C: Genetics of human obesity: research directions. FASEB J 1997, 11:937-945.