Department 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.
Diabetes. 2012 Feb;61(2):281-91. doi: 10.2337/db11-0649. Epub 2011 Dec 16.
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.
GPR55 是一种假定的大麻素受体，而 l-α-溶血磷脂酰肌醇（LPI）是其唯一已知的内源性配体。我们研究了 1）GPR55 是否在脂肪和肝脏中表达；2）GPR55 和 LPI 与多种代谢参数的相关性；3）LPI 对人脂肪细胞的作用。我们分析了两个独立队列的肥胖和瘦人群体的 CB1、CB2 和 GPR55 基因表达和循环 LPI 水平，这些群体均具有正常或受损的葡萄糖耐量和 2 型糖尿病。体外实验用于测量细胞内钙和脂质积累。与非肥胖受试者相比，肥胖受试者的脂肪组织中 GPR55 水平增加，而 2 型糖尿病肥胖患者的 GPR55 水平进一步增加。内脏脂肪组织 GPR55 与体重、BMI 和体脂肪百分比呈正相关，尤其是在女性中。肥胖和 2 型糖尿病受试者的肝 GPR55 基因表达相似。肥胖患者的循环 LPI 水平升高，且在女性中与脂肪百分比和 BMI 相关。LPI 增加了内脏脂肪组织外植体中脂肪生成基因的表达和分化的内脏脂肪细胞中的细胞内钙。这些发现表明，LPI/GPR55 系统与人类肥胖呈正相关。
