Effects of telmisartan on expression of PPARγ in subcutaneous and visceral adipose tissue in OLETF rats

Abstract

Objective To explore the regulation of telmisartan on expression of peroxisome proliferator-activated receptor(PPAR) 1 and PPARγ2 in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in high-fat diet fed OLETF rats and their tissue difference.Methods Thirty four-week-old male OLETF rats were selected and 12 gender-and age-matched Long-Evans Tokushima Otsuka(LETO) rats were used as normal control.From 8 weeks of age,the OLETF rats were fed with high-fat diet.At 22 weeks of age,there was no case of impaired glucose tolerance or type 2 diabetes mellitus in OLETF rats tested by oral glucose tolerance test (OGTT).Then,these pre-diabetic OLETF rats were divided into telmisartan group (O-T group,5 mg· kg-1 · d-1,n =10),pioglitazone group (O-P group,10 mg · kg-1 · d-1,n=8),and untreated control group (O-T group,n =10) according to the radom number table.LETO (n =12) rats were used as control group.OGTT was carried out at 48 weeks of age,and homeostasis model assessment of insulin resistance(HOMA-IR)was evaluated.Serum PPARγwas measured using ELISA.The mRNA levels of PPARγ1 and PPARγ2 in different fatty tissues were determined by real-time PCR.The adipocyte sizes were also assessed.Results Compared with O-C group,the PPARγ2 level in SAT was significantly up-regulated in O-T group(P ＜0.01),while no difference was observed between O-T and O-P group.In addition,both PPARγ1 and PPARγ2 mRNA levels in VAT were up-regulated in O-T group (P ＜0.01).There was a negative correlation bctween HOMA-IR and PPARγ2 mRNA expression in VAT (ρ =-0.369,P =0.021).Compared with O-C group,the adipose cell size was decreased by 56％ in O-T group.Conclusion Telnisartan can at least partially up-regulate the expression of PPARγ,1 and PPARγ2 in SAT and VAT,decrease the adipose cell size,and improve insulin sensitivity by activating PPARγ. Key words: Telmisartan; Type 2 diabetes mellitus; Peroxisome proliferator-activated receptor γ; Adipose tissue