title: PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women.
abstract: Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P=0.022) and higher circulating TNF-α (P=0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P=0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue.
authors.affiliation: Unit of Research in Medical Nutrition, Centro Médico Nacional "Siglo XXI", Mexico. marsau2@prodigy.net.mx
authors.forename: Mardia
authors.initials: M
authors.lastname: López-Alarcón
authors.forename: Maricela
authors.initials: M
authors.lastname: Rodríguez-Cruz
authors.forename: Victor Saúl
authors.initials: VS
authors.lastname: Vital-Reyes
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Zavala-Ortega
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Hinojosa-Cruz
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.forename: José
authors.initials: J
authors.lastname: Fernández
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D000409:Alanine / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011392:Proline / Q000235:genetics*
chemical_list: D017931:DNA Primers; D047495:PPAR gamma; D011392:Proline; D008071:Lipoprotein Lipase; D000409:Alanine