Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 May;13(3):259-278.
doi: 10.2217/fca-2016-0059. Epub 2017 Jun 5.

PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α

Lu Han  1   2 , Wen-Jun Shen  1   2 , Stefanie Bittner  1 , Fredric B Kraemer  1   2 , Salman Azhar  1   2
Affiliations
Review

PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α

Lu Han et al. Future Cardiol. 2017 May.

Abstract

This article provides a comprehensive review about the molecular and metabolic actions of PPAR-α. It describes its structural features, ligand specificity, gene transcription mechanisms, functional characteristics and target genes. In addition, recent progress with the use of loss of function and gain of function mouse models in the discovery of diverse biological functions of PPAR-α, particularly in the vascular system and the status of the development of new single, dual, pan and partial PPAR agonists (PPAR modulators) in the clinical management of metabolic diseases are presented. This review also summarizes the clinical outcomes from a large number of clinical trials aimed at evaluating the atheroprotective actions of current clinically used PPAR-α agonists, fibrates and statin-fibrate combination therapy.

Keywords: NAFLD; cardiovascular disease; dyslipidemia; fibrates; insulin resistance; lipid and glucose homeostasis; metabolic diseases; obesity.

PubMed Disclaimer

Conflict of interest statement

Financial & competing interests disclosure

This work was supported by the Office of Research and Development, Medical Service, Department of Veterans Affairs, and grants from the National Institutes of Health (HL033881 and HL092473). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Schematic representation of the principal domains of PPARs.
PPAR-α, PPARβ/δ and PPARγ possess a modular structure and composed of five principal domains: AF-1, a ligand-independent activation domain in the A/B region; DBD, D domain; the hinge region; LBD and AF-2 activation domain. AF: Activation factor; DBD: DNA-binding domain; LBD: Ligand-binding domain.
<b>Figure 2.</b>
Figure 2.. PPAR-mediated gene regulation.
Under unliganded state, PPAR/RXR heterodimers are bound to multicomponent repressors containing histone deacetylase activity, such as NcoR and SMART, thereby inhibiting gene transcription (A). Ligand binding to either PPAR or RXR causes displacement of bound repressors, recruitment of co-activators such as SRC-1 and the PBP and transcriptional modulation (primarily activation) of gene transcription (B). DBD: DNA-binding domain; NcoR: Nuclear receptor corepressor; PBP: PPAR-binding protein; PPRE: Peroxisome proliferator response element; RXR: Retinoid X receptor; SMART: Silencing mediator for retinoid and thyroid hormone receptor; SRC: Steroid receptor co-activator.
See this image and copyright information in PMC

References

    1. WHO. Cardiovascular disease. 2016. www.who.int/cardiovascular_disease/en/
    1. CDC and Prevention, Division for Heart Disease and Stroke Prevention. Heart disease fact sheet. 2016. www.cdc.gov/dhdsp/data_statistics/fact_sheets/docs/fs_heart_disease.pdf
    1. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67(5):968–977. - PubMed
    1. Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Circulation. 2006;113(6):898–918. - PubMed
    1. Mathew B, Francis L, Kayalar A, Cone J. Obesity: effects on cardiovascular disease and its diagnosis. J. Am. Board Fam. Med. 2008;21(6):562–568. - PubMed