The apelin/APJ system as a therapeutic target in metabolic diseases

ABSTRACT

Introduction: Apelin, a bioactive peptide, is the endogenous ligand of APJ, a G protein-coupled receptor which is widely expressed in peripheral tissues and in the central nervous system. The apelin/APJ system is involved in the regulation of various physiological functions and is a therapeutic target in different pathologies; the development of APJ agonists and antagonists has thus increased.

Area covered: This review focuses on the in vitro and in vivo metabolic effects of apelin in physiological conditions and in the context of metabolic diseases.

Expert opinion: In experimental models, novel APJ agonists are efficient in vivo, to treat metabolic diseases and associated complications. However, more clinical trials are necessary to determine whether molecules that target APJ could become an alternative therapeutic strategy in the treatment of metabolic diseases and associated complications.

KEYWORDS:

• Apelin
• obesity
• type 2 diabetes
• energy metabolism
• apelin/APJ system

Article highlights

• Apelin, is a bioactive peptide and the ligand of APJ (a G protein-coupled receptor). They form the apelin/APJ system, which is widely expressed in different tissues, organs and in the central nervous system.

• Apelin is considered a new player both in glucose and lipid metabolism, AMPK activation being a major signaling target involved in apelin metabolic effects such as glucose transport or oxidation of fatty acids.

• The apelin/APJ system has a large spectrum of therapeutic potential in metabolic diseases since apelin has anti-diabetic properties and reduces comorbidities associated with type 2 diabetes such as cardiovascular diseases and diabetic nephropathy.

• A first clinical trial in healthy overweight volunteers has shown that apelin has insulin-sensitizing properties.

• Different APJ agonists have the potential to emerge as alternative therapeutic agents for the treatment of metabolic diseases.

Declaration of interest

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by a clinical research grant from SFD (Société Francophone du Diabète - French Diabetes Society), a French Midi-Pyrénées region APRTCN grant (call for proposals in clinical research transfer and standardization) and INSERM.