Gabriella Garufi1, Attila A Seyhan, Magdalena Pasarica. 1. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida, USA; Sanford Burnham Medical Research Institute, Orlando, Florida, USA.
Abstract
OBJECTIVES: Rarefaction and inflammation of adipose tissue contributes to insulin resistance in obesity. It was hypothesized that angiostatic secreted frizzled-related protein 4 (SFRP4) causes adipose tissue rarefaction and leads to inflammation and ultimately insulin resistance in obese patients. METHODS: Abdominal subcutaneous adipose tissue (AbdAT), gluteal subcutaneous adipose tissue (GlutAT), and blood from 15 lean and obese subjects were collected. Circulating-SFRP4 was measured by ELISA. Body composition was measured by DEXA and insulin sensitivity by the euglycemic hyperinsulinemic clamp. Adipose tissue was analyzed using qRT-PCR for mRNA gene expression, Luminex system for tissue cytokine release, immunohistochemistry for labeling adipose capillaries, and osmium fixation and Coulter counting for adipocyte sizing. RESULTS: Circulating-SFRP4 was higher in obese vs. lean subjects (137.8 ± 33.6 ng ml(-1) vs. 64.1 ± 23.8 ng ml(-1) , P < 0.05). Circulating-SFRP4 significantly (P < 0.05) correlated with body fat percentage (R = 0.07), body mass index (R = 0.07), insulin sensitivity (R = -0.66). Circulating-SFRP4 correlated with AbdAT-VEGF (R = -0.67, P < 0.05), AbdAT-capillary density (R = -0.65, P < 0.05), secreted-MIP1α (R = 0.74), and AbdAT-SFRP4 mRNA (R = 0.60). AbdAT-SFRP4 mRNA significantly correlated with AbdAT-capillary density (R = 0.71, P < 0.05), but not with AbdAT mean adipocyte size. There was no difference between AbdAT-SFRP4 and GlutAT-SFRP4 mRNA. Interestingly, GlutAT-SFRP4 correlated with AbdAT mean adipocyte size (P < 0.05). CONCLUSIONS: The results suggested that AbdAT is a major contributor for circulating-SFRP4 and that SFRP4 has an important role in obese adipose tissue pathophysiology.
OBJECTIVES: Rarefaction and inflammation of adipose tissue contributes to insulin resistance in obesity. It was hypothesized that angiostatic secreted frizzled-related protein 4 (SFRP4) causes adipose tissue rarefaction and leads to inflammation and ultimately insulin resistance in obesepatients. METHODS: Abdominal subcutaneous adipose tissue (AbdAT), gluteal subcutaneous adipose tissue (GlutAT), and blood from 15 lean and obese subjects were collected. Circulating-SFRP4 was measured by ELISA. Body composition was measured by DEXA and insulin sensitivity by the euglycemic hyperinsulinemic clamp. Adipose tissue was analyzed using qRT-PCR for mRNA gene expression, Luminex system for tissue cytokine release, immunohistochemistry for labeling adipose capillaries, and osmium fixation and Coulter counting for adipocyte sizing. RESULTS: Circulating-SFRP4 was higher in obese vs. lean subjects (137.8 ± 33.6 ng ml(-1) vs. 64.1 ± 23.8 ng ml(-1) , P < 0.05). Circulating-SFRP4 significantly (P < 0.05) correlated with body fat percentage (R = 0.07), body mass index (R = 0.07), insulin sensitivity (R = -0.66). Circulating-SFRP4 correlated with AbdAT-VEGF (R = -0.67, P < 0.05), AbdAT-capillary density (R = -0.65, P < 0.05), secreted-MIP1α (R = 0.74), and AbdAT-SFRP4 mRNA (R = 0.60). AbdAT-SFRP4 mRNA significantly correlated with AbdAT-capillary density (R = 0.71, P < 0.05), but not with AbdAT mean adipocyte size. There was no difference between AbdAT-SFRP4 and GlutAT-SFRP4 mRNA. Interestingly, GlutAT-SFRP4 correlated with AbdAT mean adipocyte size (P < 0.05). CONCLUSIONS: The results suggested that AbdAT is a major contributor for circulating-SFRP4 and that SFRP4 has an important role in obese adipose tissue pathophysiology.
Authors: Sindre Lee; Frode Norheim; Torgrim M Langleite; Hanne L Gulseth; Kåre I Birkeland; Christian A Drevon Journal: Diabetologia Date: 2019-04-22 Impact factor: 10.122
Authors: Meaghan A Delaney; Ying-Wooi Wan; Gyoung-Eun Kim; Chad J Creighton; Margaret G Taylor; Ramya Masand; Andrew Park; Cecilia Valdes; William Gibbons; Zhandong Liu; Matthew L Anderson Journal: J Clin Endocrinol Metab Date: 2017-09-01 Impact factor: 5.958