title: Rosiglitazone inhibits expression and secretion of PEDF in adipose tissue and liver of male SD rats via a PPAR-γ independent mechanism.
abstract: Pigment epithelium-derived factor (PEDF) plays an important role in insulin resistance (IR). The study aims to investigate the effect of rosiglitazone, an insulin sensitizer, on PEDF production and release both in vivo and in vitro. Male SD rats were divided into normal control group, high-fat group, and rosiglitazone group. Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 adipocytes and HepG2 cells were established by the hyperinsulinemic method. Glucose uptake was examined to validate IR of adipocytes, and phosphorylation of protein kinase B and glycogen synthesis kinase 3β were examined to validate IR of HepG2 cells. Rosiglitazone, 2-chloro-5-nitro-N-phenylbenzamide (GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ), and compound C (inhibitor of AMP-activated protein kinase [AMPK]) were used for the in vitro intervention. In vivo, the high-fat group showed increased serum PEDF levels, which negatively correlated with insulin sensitivity, whereas the rosiglitazone treatment decreased the serum PEDF and down-regulated PEDF expression in fat and liver of the obese rats, concomitant with significantly enhanced insulin sensitivity. In vitro, the IR cells showed increased PEDF secretion and expression, whereas rosiglitazone lowered PEDF secretion and expression, accompanied with increased insulin sensitivity. Interestingly, combination with 2-chloro-5-nitro-N-phenylbenzamide did not influence the effect of rosiglitazone on PEDF. However, rosiglitazone stimulated AMPK phosphorylation in fat and liver of the obese rats, whereas in vitro, when combined with compound C, the effect of rosiglitazone on PEDF was abrogated. In summary, rosiglitazone inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation rather than peroxisome proliferator-activated receptor-γ, and changes of PEDF induced by rosiglitazone are closely associated with IR improvement.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.forename: Huang
authors.initials: H
authors.lastname: Zhou
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lv
authors.forename: Lulu
authors.initials: L
authors.lastname: Liu
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.forename: Rufei
authors.initials: R
authors.lastname: Gao
authors.forename: Shumei
authors.initials: S
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Cheng
authors.forename: Qifu
authors.initials: Q
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D005136:Eye Proteins / Q000097:blood*; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000097:blood*; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D015843:Serpins / Q000097:blood*; D045162:Thiazolidinediones / Q000737:chemistry*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D055372:AMP-Activated Protein Kinases; D005136:Eye Proteins; D007004:Hypoglycemic Agents; D009414:Nerve Growth Factors; D047495:PPAR gamma; D000077154:Rosiglitazone; D015843:Serpins; D045162:Thiazolidinediones; D000099174:Pigment Epithelium-Derived Factor