Molecular physiopathology of obesity-related diseases: multi-organ integration by GRK2

Abstract

Obesity is a worldwide problem that has reached epidemic proportions both in developed and developing countries. The excessive accumulation of fat poses a risk to health since it favours the development of metabolic alterations including insulin resistance and tissue inflammation, which further contribute to the progress of the complex pathological scenario observed in the obese. In this review we put together the different outcomes of fat accumulation and insulin resistance in the main insulin-responsive tissues, and discuss the role of some of the key molecular routes that control disease progression both in an organ-specific and also in a more systemic manner. In particular, we focus on the importance of studying the integrated regulation of different organs and pathways that contribute to the global pathophysiology of this condition with a specific emphasis on the role of emerging key molecular nodes such as the G protein-coupled receptor kinase 2 (GRK2) signalling hub.

• G protein-coupled receptor kinase
• insulin signalling
• obesity
• insulin resistance
• type 2 diabetes
• adipose tissue
• liver steatosis
• hypertension
• cardiac hypertrophy

Acknowledgements

Work in our laboratories is supported by The Cardiovascular Network (RD12/0042/0012 and RD12/0042/0024) (to FM and MS) and grant PI13/01488 (to AMB) from Ministerio Sanidad y Consumo-Instituto de Salud Carlos III, Spain; grants SAF2014-55511-R and SAF2012-36400 from Ministerio de Economía y Competitividad (MINECO), Spain (to FM-CM and MS); S2010/BMD-2332 (INDISNET) from Comunidad de Madrid, Spain (to FM); an EFSD-Novo Nordisk Grant (to FM) and Fundación Ramón Areces (to CM and AMB). EL was recipient of a FPU fellowship from Ministerio de Educación-Spain; MCS is a recipient of a FPI fellowship from UAM; RVB is a recipient of a Postdoctoral Contract and AMB is a recipient of a Ramon y Cajal Contract (RyC-2010-06473) both from MINECO, Spain.

Declaration of interest

The authors report no declarations of interest.