Distinct but complementary contributions of PPAR isotypes to energy homeostasis
Vanessa Dubois, … , Philippe Lefebvre, Bart Staels
Vanessa Dubois, … , Philippe Lefebvre, Bart Staels
Published April 3, 2017
Citation Information: J Clin Invest. 2017;127(4):1202-1214. https://doi.org/10.1172/JCI88894.
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Distinct but complementary contributions of PPAR isotypes to energy homeostasis

Abstract

Peroxisome proliferator–activated receptors (PPARs) regulate energy metabolism and hence are therapeutic targets in metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. While they share anti-inflammatory activities, the PPAR isotypes distinguish themselves by differential actions on lipid and glucose homeostasis. In this Review we discuss the complementary and distinct metabolic effects of the PPAR isotypes together with the underlying cellular and molecular mechanisms, as well as the synthetic PPAR ligands that are used in the clinic or under development. We highlight the potential of new PPAR ligands with improved efficacy and safety profiles in the treatment of complex metabolic disorders.

Authors

Vanessa Dubois, Jérôme Eeckhoute, Philippe Lefebvre, Bart Staels

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Figure 3

PPARβ/δ activation enhances glucose and lipid homeostasis.

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PPARβ/δ activation enhances glucose and lipid homeostasis. In SKM, PPARβ...
In SKM, PPARβ/δ activation (effects are indicated in pink) favors fiber type switching toward type I oxidative fibers, which have a higher glucose-handling capacity compared with type II fibers. PPARβ/δ also augments FAO in SKM, liver, and WAT and enhances hepatic glucose metabolism and pancreatic β cell function. PPARβ/δ activation decreases FAs, triglycerides, and LDL-C and increases HDL-C levels in blood. Metabolic effects of PPARβ/δ agonism also take place in brain and gut.