title: Low density lipoprotein receptor-related protein 1 is upregulated in epicardial fat from type 2 diabetes mellitus patients and correlates with glucose and triglyceride plasma levels.
abstract: Lipoprotein receptor expression plays a crucial role in the pathophysiology of adipose tissue in in vivo models of diabetes. However, there are no studies in diabetic patients. The aims of this study were to analyze (a) low-density lipoprotein receptor-related protein 1 (LRP1) and very low-density lipoprotein receptor (VLDLR) expression in epicardial and subcutaneous fat from type 2 diabetes mellitus compared with nondiabetic patients and (b) the possible correlation between the expression of these receptors and plasmatic parameters. Adipose tissue biopsy samples were obtained from diabetic (n = 54) and nondiabetic patients (n = 22) undergoing cardiac surgery before the initiation of cardiopulmonary bypass. Adipose LRP1 and VLDLR expression was analyzed at mRNA level by real-time PCR and at protein level by Western blot analysis. Adipose samples were also subjected to lipid extraction, and fat cholesterol ester, triglyceride, and free cholesterol contents were analyzed by thin-layer chromatography. LRP1 expression was higher in epicardial fat from diabetic compared with nondiabetic patients (mRNA 17.63 ± 11.37 versus 7.01 ± 4.86; P = 0.02; protein 11.23 ± 7.23 versus 6.75 ± 5.02, P = 0.04). VLDLR expression was also higher in epicardial fat from diabetic patients but only at mRNA level (231.25 ± 207.57 versus 56.64 ± 45.64, P = 0.02). No differences were found in the expression of LRP1 or VLDLR in the subcutaneous fat from diabetic compared with nondiabetic patients. Epicardial LRP1 and VLDLR mRNA overexpression positively correlated with plasma triglyceride levels (R(2) = 0.50, P = 0.01 and R(2) = 0.44, P = 0.03, respectively) and epicardial LRP1 also correlated with plasma glucose levels (R(2) = 0.33, P = 0.03). These results suggest that epicardial overexpression of certain lipoprotein receptors such as LRP1 and VLDLR expression may play a key role in the alterations of lipid metabolism associated with type 2 diabetes mellitus.
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, UAB, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Nasarre
authors.forename: O
authors.initials: O
authors.lastname: Juan-Babot
authors.forename: P
authors.initials: P
authors.lastname: Gastelurrutia
authors.forename: A
authors.initials: A
authors.lastname: Llucia-Valldeperas
authors.forename: L
authors.initials: L
authors.lastname: Badimon
authors.forename: A
authors.initials: A
authors.lastname: Bayes-Genis
authors.forename: V
authors.initials: V
authors.lastname: Llorente-Cortés
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010496:Pericardium / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor