Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination - PubMed (original) (raw)
Comparative Study
. 2005 Dec;54(12):3358-70.
doi: 10.2337/diabetes.54.12.3358.
Affiliations
- PMID: 16306350
- DOI: 10.2337/diabetes.54.12.3358
Comparative Study
Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination
Atsushi Tsuchida et al. Diabetes. 2005 Dec.
Abstract
We examined the effects of activation of peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, and both of them in combination in obese diabetic KKAy mice and investigated the mechanisms by which they improve insulin sensitivity. PPARalpha activation by its agonist, Wy-14,643, as well as PPARgamma activation by its agonist, rosiglitazone, markedly improved insulin sensitivity. Interestingly, dual activation of PPARalpha and -gamma by a combination of Wy-14,643 and rosiglitazone showed increased efficacy. Adipocyte size in Wy-14,643-treated KKAy mice was much smaller than that of vehicle- or rosiglitazone-treated mice, suggesting that activation of PPARalpha prevents adipocyte hypertrophy. Moreover, Wy-14,643 treatment reduced inflammation and the expression of macrophage-specific genes in white adipose tissue (WAT). Importantly, Wy-14,643 treatment upregulated expression of the adiponectin receptor (AdipoR)-1 and AdipoR2 in WAT, which was decreased in WAT of KKAy mice compared with that in nondiabetic control mice. Furthermore, Wy-14,643 directly increased expression of AdipoRs and decreased monocyte chemoattractant protein-1 expression in adipocytes and macrophages. Rosiglitazone increased serum adiponectin concentrations and the ratio of high molecular weight multimers of adiponectin to total adiponectin. A combination of rosiglitazone and Wy-14,643 increased both serum adiponectin concentrations and AdipoR expression in WAT. These data suggest that PPARalpha activation prevents inflammation in WAT and that dual activation of PPARalpha and -gamma enhances the action of adiponectin by increasing both adiponectin and AdipoRs, which can result in the amelioration of obesity-induced insulin resistance.
Similar articles
- Therapeutic potential of the dual peroxisome proliferator activated receptor (PPAR)α/γ agonist aleglitazar in attenuating TNF-α-mediated inflammation and insulin resistance in human adipocytes.
Massaro M, Scoditti E, Pellegrino M, Carluccio MA, Calabriso N, Wabitsch M, Storelli C, Wright M, De Caterina R. Massaro M, et al. Pharmacol Res. 2016 May;107:125-136. doi: 10.1016/j.phrs.2016.02.027. Epub 2016 Mar 11. Pharmacol Res. 2016. PMID: 26976796 - PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.
Hulsmans M, Geeraert B, Arnould T, Tsatsanis C, Holvoet P. Hulsmans M, et al. PLoS One. 2013 Apr 19;8(4):e62253. doi: 10.1371/journal.pone.0062253. Print 2013. PLoS One. 2013. PMID: 23620818 Free PMC article. - The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo.
Li YY, Wu HS, Tang L, Feng CR, Yu JH, Li Y, Yang YS, Yang B, He QJ. Li YY, et al. Pharmacol Res. 2007 Oct;56(4):335-43. doi: 10.1016/j.phrs.2007.08.002. Epub 2007 Aug 9. Pharmacol Res. 2007. PMID: 17889553 - Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases.
Yamauchi T, Kadowaki T. Yamauchi T, et al. Int J Obes (Lond). 2008 Dec;32 Suppl 7:S13-8. doi: 10.1038/ijo.2008.233. Int J Obes (Lond). 2008. PMID: 19136982 Review. - Novel approach to treat insulin resistance, type 2 diabetes, and the metabolic syndrome: simultaneous activation of PPARalpha, PPARgamma, and PPARdelta.
Evans JL, Lin JJ, Goldfine ID. Evans JL, et al. Curr Diabetes Rev. 2005 Aug;1(3):299-307. doi: 10.2174/157339905774574365. Curr Diabetes Rev. 2005. PMID: 18220606 Review.
Cited by
- Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction.
Engin A. Engin A. Adv Exp Med Biol. 2024;1460:431-462. doi: 10.1007/978-3-031-63657-8_15. Adv Exp Med Biol. 2024. PMID: 39287861 Review. - Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy.
Habib S. Habib S. World J Gastrointest Pathophysiol. 2024 Aug 22;15(4):93606. doi: 10.4291/wjgp.v15.i4.93606. World J Gastrointest Pathophysiol. 2024. PMID: 39220834 Free PMC article. Review. - Crosstalk between Lipid Metabolism and Bone Homeostasis: Exploring Intricate Signaling Relationships.
Xiao H, Li W, Qin Y, Lin Z, Qian C, Wu M, Xia Y, Bai J, Geng D. Xiao H, et al. Research (Wash D C). 2024 Aug 20;7:0447. doi: 10.34133/research.0447. eCollection 2024. Research (Wash D C). 2024. PMID: 39165638 Free PMC article. - New advances of adiponectin in regulating obesity and related metabolic syndromes.
Han Y, Sun Q, Chen W, Gao Y, Ye J, Chen Y, Wang T, Gao L, Liu Y, Yang Y. Han Y, et al. J Pharm Anal. 2024 May;14(5):100913. doi: 10.1016/j.jpha.2023.12.003. Epub 2023 Dec 13. J Pharm Anal. 2024. PMID: 38799237 Free PMC article. Review. - The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.
Cooreman MP, Butler J, Giugliano RP, Zannad F, Dzen L, Huot-Marchand P, Baudin M, Beard DR, Junien JL, Broqua P, Abdelmalek MF, Francque SM. Cooreman MP, et al. Nat Commun. 2024 May 10;15(1):3962. doi: 10.1038/s41467-024-47919-9. Nat Commun. 2024. PMID: 38730247 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials