The role of hypothalamic AMP-activated protein kinase in ovariectomy-induced obesity in rats.
OBJECTIVE
Adenosine monophosphate-activated protein kinase (AMPK) acts as a cellular energy sensor, being activated during states of low energy charge. Hypothalamic AMPK is altered by hormonal and metabolic signals and mediates the feeding response. The aims of this study were to examine whether the phosphorylation of AMPKα in the hypothalamus is affected by ovariectomy (Ovx) and thus would be involved in the development of obesity in rats.


METHODS
Body weight, food intake, hypothalamic phosphorylated AMPKα (pAMPKα) protein expression, and plasma leptin and adiponectin levels were measured in female rats after either Ovx or sham operations. These patterns were also observed after treatment with 17β-estradiol, compound C, and leptin in Ovx rats.


RESULTS
Compared with control rats, Ovx led to increased body weight and food intake at 2 to 8 weeks after operation. Meanwhile, plasma leptin and adiponectin levels and hypothalamic pAMPKα expression were significantly increased after Ovx. Replacement of estradiol significantly reversed these effects. Treatment with compound C, an AMPKα inhibitor, for 1 week produced a reduction in food intake, body weight, and plasma leptin and adiponectin levels. Meanwhile, these effects were reversed upon withdrawal of compound C. In addition, central injection of leptin also significantly reduced body weight, food intake, plasma leptin and adiponectin levels, and hypothalamic pAMPKα expression relative to those of the Ovx group.


CONCLUSIONS
Increased hypothalamic pAMPKα expression may contribute to hyperphagia during the development of Ovx-induced obesity in rats.
Tsai
Yung-Chieh
YC
Center for Reproductive Medicine, Chi Mei Foundation Hospital, Tainan, Taiwan.
Lee
Yen-Mei
YM
Lam
Kwok-Keung
KK
Wu
Yu-Chuan
YC
Yen
Mao-Hsiung
MH
Cheng
Pao-Yun
PY
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D004435:Eating; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000201:enzymology*; D020738:Leptin / Q000097:blood / Q000502:physiology; D023421:Models, Animal; D009765:Obesity / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D052242:Adiponectin; D020738:Leptin; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; D004958:Estradiol; D055372:AMP-Activated Protein Kinases