Objective      To explore the possible mechanism of metformin in up-regulation of serum soluble leptin receptor (sOB-R) in mice.       Methods      Forty-two C57BL/6 mice

aged  from 6 to 8 weeks

with normal body weight (17.02±1.91 g) were randomly divided into 2 groups

which were fed with standard chow diet (CD) (n=21) and high-fat diet (HF) (n=21)

respectively

for 5 months. The mice in each group were then divided into 3 subgroups (n=7) and administrated with water

metformin 50 mg/(kg·d) and metformin 200 mg/(kg·d)

respectively

via gastric lavage once a day for 15 d. Serum sOB-R was determined by ELISA. Expressions of total leptin receptor (OB-Rt) and major membrane-bound leptin receptor isoforms (OB-Ra

OB-Rb

OB-Rc

and OB-Rd) in liver and kidney of the mice were determined by real-time PCR. The expression of A Disintegrin And Metalloproteinase 10 (ADAM10) and ADAM17

which participated in ectodomain shedding of leptin receptor

was detected by real-time PCR and Western blotting.       Results      After metformin treatment

serum sOB-R levels were increased in both CD group and HF group in a dose-dependent manner

for a more detailed

serum sOB-R levels were increased in metformin 200 mg/（kg·d） subgroup compared with the other 2 subgroups in CD group (P0.05)

while they were increased significantly in 2 metformin treatment subgroups compared to non-treatment subgroup in HF group(P0.01). Moreover

compared with the non-treatment mice

the expression of OB-Rt mRNA in the liver was dose-dependently up-regulated in the metformine-treated mice of the CD group as well as the HF group

and the expression in the HF group was increased more significantly

by the way

the trend was very similar to the level of sOB-R. The OB-Ra

OB-Rc and OB-Rd had the same increase trend as OB-Rt in the liver

but not in kidney. Meanwhile

Adam10 and Adam17 mRNA and protein levels were not significantly changed in both liver and kidney tissues of the CD and HF groups with metformin treatment.        Conclusion      Metformin up-regulates serum sOB-R through increasing the expression of leptin receptors

especially short leptin receptor isoforms

in the liver.