PPARs and their metabolic modulation: New mechanisms for transcriptional regulation?

W. Ahmed, O. Ziouzenkova, J. Brown, P. Devchand, S. Francis, M. Kadakia, T. Kanda, G. Orasanu, M. Sharlach, F. Zandbergen, J. Plutzky

研究成果: Article査読

113 被引用数 (Scopus)

抄録

Peroxisome proliferator-activated receptors (PPARs) as ligand-activated nuclear receptors involved in the transcriptional regulation of lipid metabolism, energy balance, inflammation, and atherosclerosis are at the intersection of key pathways involved in the pathogenesis of diabetes and cardiovascular disease. Synthetic PPAR agonists like fibrates (PPAR-α) and thiazolidinediones (PPAR-γ) are in therapeutic use to treat dyslipidaemia and diabetes. Despite strong encouraging in vitro, animal model, and human surrogate marker studies with these agents, recent prospective clinical cardiovascular trials have yielded mixed results, perhaps explained by concomitant drug use, study design, or a lack of efficacy of these agents on cardiovascular disease (independent of their current metabolic indications). The use of PPAR agents has also been limited by untoward effects. An alternative strategy to PPAR therapeutics is better understanding PPAR biology, the nature of natural PPAR agonists, and how these molecules are generated. Such insight might also provide valuable information about pathways that protect against the metabolic problems for which PPAR agents are currently indicated. This approach underscores the important distinction between the effects of synthetic PPAR agonists and the unequivocal biologic role of PPARs as key transcriptional regulators of metabolic and inflammatory pathways relevant to diabetes and atherosclerosis.

本文言語English
ページ(範囲)184-198
ページ数15
ジャーナルJournal of Internal Medicine
262
2
DOI
出版ステータスPublished - 2007 8月
外部発表はい

ASJC Scopus subject areas

  • 内科学

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