Metformin restores the penile expression of nitric oxide synthase in high-fat-fed obese rats.
Obesity is a well-known risk factor for erectile dysfunction, which is associated with reduced penile nitric oxide synthase (NOS) expression. Recently it was reported that metformin activates AMP-activated protein kinase (AMPK), which increases the expression of neuronal (n) NOS and endothelial (e) NOS. Thus, to evaluate whether metformin restores NOS expression in penile tissue, we measured penile expression of nNOS and eNOS after 4 weeks of metformin treatment (300 mg/kg/d) in 5-month-old high-fat-fed obese (HFO) rats. HFO rats have increased fat accumulation in visceral areas and marked suppression of nNOS and eNOS expression in penile tissue. However, metformin treatment decreased visceral fat deposition and restored nNOS and eNOS expression in penile tissue. The levels of AMPK and phosphorylated AMPK were also decreased in HFO rats but were subsequently elevated by metformin treatment. These results suggest that expression of NOS was suppressed by the high-fat diet but restored by metformin treatment. The effect of metformin on the expression of NOS may be associated with its activation of AMPK.
Kim
Yong-Woon
YW
Department of Urology, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Nam-Gu, Daegu 705-035, Republic of Korea.
Park
So-Young
SY
Kim
Jong-Yeon
JY
Huh
Jung-Yoon
JY
Jeon
Woo-Sung
WS
Yoon
Chang-Jun
CJ
Yun
Sung-Su
SS
Moon
Ki-Hak
KH
D000263:Adenylate Kinase / Q000097:blood; D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001835:Body Weight; D004041:Dietary Fats; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009765:Obesity / Q000201:enzymology* / Q000209:etiology; D009929:Organ Size; D010413:Penis / Q000201:enzymology*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004041:Dietary Fats; D008687:Metformin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000263:Adenylate Kinase