Leptin resistance during pregnancy in the rat.
The adipose-derived hormone leptin primarily acts in the hypothalamus to decrease appetite and increase energy expenditure, thereby maintaining body fat levels around a set point. Pregnancy is a physiological state where this feedback mechanism is not beneficial. Successful reproductive efforts are highly demanding on the resources of the mother; thus, it is imperative that the maternal body can increase energy stores without restraint. Food intake, fat mass and serum leptin concentrations increase during pregnancy in the rat, suggesting that the feedback loop between adipose tissue and appetite is disrupted and a state of leptin resistance exists. In support of this, there is an attenuation of the satiety response to exogenous leptin administration in pregnant rats. This state of leptin resistance is associated with impaired activation of the leptin-induced Janus activating kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the ventromedial nucleus of the hypothalamus (VMH) and arcuate nucleus, and reduced expression of leptin receptor mRNA in the VMH. Furthermore, pregnant rats do not show a satiety response to exogenous alpha-melanocyte stimulating hormone. This model offers the possibility of examining how hypothalamic leptin signalling can be modified in response to changes in physiological conditions.
Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Quebec, Canada. sladyman@alcor.concordia.ca
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D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004351:Drug Resistance; D025461:Feedback, Physiological; D005260:Female; D053612:Janus Kinases / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D054411:Receptors, Leptin / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects*; D015398:Signal Transduction; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology
D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D050791:STAT Transcription Factors; D000521:alpha-MSH; D053612:Janus Kinases