The L-α-lysophosphatidylinositol/GPR55 system and its potential role in human obesity

Jose Maria Moreno-Navarrete, Victoria Catalan, Lauren Whyte, Adenis Diaz-Arteaga, Rafael Vazquez-Martinez, Fernando Rotellar, Rocio Guzman, Javier Gomez-Ambrosi, Marina R. Pulido, Wendy R. Russell, Monica Imbernon, Ruth A. Ross, Maria M. Malagon, Carlos Dieguez, Jose Manuel Fernandez-Real, Gema Fruehbeck, Ruben Nogueiras

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans.

Original languageEnglish
Pages (from-to)281-291
Number of pages11
JournalDiabetes
Volume61
Issue number2
Early online date16 Feb 2011
DOIs
Publication statusPublished - Feb 2012

Keywords

  • type-2 diabetes-mellitus
  • human adipose-tissue
  • cannabinoid receptor
  • endocannabinoid system
  • energy-balance
  • sexual dimorphism
  • gene-expression
  • gastric bypass
  • ovarian-cancer
  • GPR55

Cite this

Maria Moreno-Navarrete, J., Catalan, V., Whyte, L., Diaz-Arteaga, A., Vazquez-Martinez, R., Rotellar, F., ... Nogueiras, R. (2012). The L-α-lysophosphatidylinositol/GPR55 system and its potential role in human obesity. Diabetes, 61(2), 281-291. https://doi.org/10.2337/db11-0649