[Effects of candesartan on expressions of JAK2 and PTP-1B in adipose tissue of high-fat diet-fed rats].
OBJECTIVE
To observe the effects of candesartan on the expressions of JAK2 and protein tyrosine phosphatase-1B (PTP-1B) in adipose tissue of obese rats induced by high-fat diet.


METHODS
A total of 45 male Wistar rats were randomly assigned into 3 groups of normal control (NC group), high fat diet (HF group) and high-fat diet with daily Candesartan treatment (FC group). The rats of FC group were treated with orally taken Candesartan at a dose of 8 mg/kg body weight per day. Blood chemistry and insulin were assayed at Week 16. Euglycemic-hyperinsulinemic clamp technique was performed to evaluate the peripheral insulin resistance. The expressions of JAK2 and PTP-1B in adipose tissue were confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.


RESULTS
(1) The body weight and peri-renal fat weight of HF group were significantly higher than those of FC and NC groups (all P < 0.05). (2) total cholesterol (TC) and fasting insulin (FINS) of FC group were lower than those of HF group [TC, FC group: (1.37 ± 0.39) mmol/L vs HF group: (2.01 ± 0.26) mmol/L, P < 0.05; FINS, FC group: (3.03 ± 1.37) mU/L vs HF group: (4.76 ± 2.75) mU/L, P < 0.05] while insulin sensitive index (ISI) and angiotensin II (AngII) of FC group were much higher than those of HF group [ISI, FC group: (58 ± 12) × 10(-3) vs HF group: (29 ± 9) × 10(-3), P < 0.05; AngII, FC group: (61 ± 11) mmol/L vs HF group: (52 ± 10) mmol/L, P < 0.05]. (3) The steady-state glucose infusion rate (SSGIR) of FC group was significantly higher than that of HF group [FC group: (22 ± 5) mg×kg(-1)×min(-1) vs HF group:(14 ± 4) mg×kg(-1)min(-1), P < 0.05]. (4) Both the mRNA and protein expressions of JAK2 and PTP-1B in FC group were significantly lower than those in HF group respectively.


CONCLUSIONS
There are insulin resistance and a high expression of JAK2 and PTP-1B in adipose tissue of obese rats induced by high-fat diet. And both are related with the elevated AngII level. Candesartan can reverse these effects.
Yan
Wen-hua
WH
Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China.
Pan
Chang-yu
CY
Dou
Jing-tao
JT
Ma
Fang-ling
FL
Wang
Xue-min
XM
Yang
Guo-qing
GQ
Wang
Xian-ling
XL
Mu
Yi-ming
YM
Lu
Ju-ming
JM
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D007333:Insulin Resistance; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; C081643:candesartan