Effects of a beta3-adrenergic agonist on the immune response in diet-induced (cafeteria) obese animals.
Molecules with affinity for beta3-adrenoceptors are not only effective anti-obesity agents in rodent models, but may play a role in the regulation of the immune response. The aim of the current investigation was to analyse the effects of trecadrine on the immune response in diet-induced (cafeteria) obese rats. Male Wistar rats were divided into 2 groups, the control group (C, n=9) was fed with the standard pelleted chow laboratory diet, while the other group was fed with a high-fat (cafeteria) diet. Cafeteria-fed rats were divided into two new subgroups (n=9 each), which received either i.p. saline (obese, O) or trecadrine (1mg/kg/day) (obese+trecadrine, O+T) daily for 5 weeks. Lymphocyte subpopulations and the proliferative response were determined by validated procedures. The administration of trecadrine was able to prevent the onset of obesity in cafeteria-fed rats. Trecadrine-treatment to obese animals appeared to improve the number of lymphocyte subpopulations (CD4+ and CD8+) as compared to those animals only receiving the high-fat diet, being the values of the trecadrine-treated animals on the high-fat diet similar to the control rats. However, the lymphoproliferative response when stimulated with several mitogens was markedly reduced by the cafeteria intake and was further decreased by the beta3-adrenergic administration. The spleen mRNA expression level of UCP2, PPARgamma and Ob-Rb were not affected by the trecadrine treatment. Summing up, at the immune system level, trecadrine administration increased the proportion of CD4+ spleen lymphocytes, although it was not able to restore the lymphocyte proliferative response which was depressed.
Dept. of Physiology and Nutrition, University of Navarra, 31008 Pamplona, Spain.
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Martínez
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D000273:Adipose Tissue / Q000187:drug effects; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000821:Animal Feed; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D005990:Glycerol / Q000097:blood; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis; D014280:Triglycerides / Q000097:blood; D000071246:Uncoupling Protein 2
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001592:Benzyl Alcohols; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C101319:trecadrine; D002784:Cholesterol; D005990:Glycerol