The L-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity
- José María Moreno-Navarrete1,
- Victoria Catalán2,
- Lauren Whyte3,
- Adenis Díaz-Arteaga4,
- Rafael Vázquez-Martínez5,
- Fernando Rotellar2,
- Rocío Guzmán5,
- Javier Gómez-Ambrosi2,
- Marina R. Pulido5,
- Wendy R. Russell6,
- Mónica Imbernón4,
- Ruth A. Ross3,
- María M. Malagón5,
- Carlos Dieguez4,
- José Manuel Fernández-Real1,
- Gema Frühbeck2 and
- Ruben Nogueiras4⇓
- 1Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomédica de Girona Catalonia, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Girona, Spain
- 2Metabolic Research Laboratory, Clínica Universidad de Navarra, University of Navarra, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Pamplona, Spain
- 3Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, U.K.
- 4Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain
- 5Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigaciones Biomédicas de Córdoba, University of Córdoba, Córdoba, Spain
- 6Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, Scotland, U.K.
- Corresponding author: Ruben Nogueiras, .
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.
- Received May 17, 2011.
- Accepted November 1, 2011.
- © 2012 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.