From feeding one to feeding many: hormone‐induced changes in bodyweight homeostasis during pregnancy
- 14 January 2008
- journal article
- review article
- Published by Wiley in Journal Of Physiology-London
- Vol. 586 (2), 387-397
- https://doi.org/10.1113/jphysiol.2007.146316
Abstract
Pregnancy is associated with hyperphagia, increased fat mass, hyperleptinaemia and hyperprolactinaemia. The neuroendocrine control of bodyweight involves appetite-regulating centres in the hypothalamus, containing both orexigenic and anorexigenic neurons that express leptin receptors (LepR). In the rat, central leptin resistance develops during mid pregnancy, well after hyperphagia becomes apparent, to negate the appetite suppressing effects of leptin. We have investigated the hypothalamic response to leptin during pregnancy and examined the role of pregnancy hormones in inducing these changes. We have shown that there are multiple levels of leptin resistance during pregnancy. Despite elevated serum leptin, neuropeptide Y and agouti related peptide mRNA in the arcuate nucleus are not suppressed and may even be increased during pregnancy. LepR mRNA and leptin-induced pSTAT3 expression, however, are relatively normal in the arcuate nucleus. In contrast, both LepR and leptin-induced pSTAT3 are reduced in the ventromedial hypothalamic nucleus. Injecting alpha-melanocyte-stimulating hormone (alpha-MSH) into the brain, to bypass the first-order leptin-responsive neurons in the arcuate nucleus, also fails to suppress food intake during pregnancy, suggesting that pregnancy is also a melanocortin-resistant state. Using a pseudopregnant rat model, we have demonstrated that in addition to the changes in maternal ovarian steroid secretion, placental lactogen production is essential for the induction of leptin resistance in pregnancy. Thus, hormonal changes associated with pregnancy induce adaptive changes in the maternal hypothalamus, stimulating food intake and then allowing elevated food intake to be maintained in the face of elevated leptin levels, resulting in fat deposition to provide energy stores in preparation for the high metabolic demands of late pregnancy and lactation.This publication has 98 references indexed in Scilit:
- Appropriate Inhibition of Orexigenic Hypothalamic Arcuate Nucleus Neurons Independently of Leptin Receptor/STAT3 SignalingJournal of Neuroscience, 2007
- Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist despite leptin resistanceNeurobiology of Aging, 2004
- STAT3 signalling is required for leptin regulation of energy balance but not reproductionNature, 2003
- Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesityJCI Insight, 2000
- Gestational Profile of Leptin Messenger Ribonucleic Acid (mRNA) Content in the Placenta and Adipose Tissue in the Rat, and Regulation of the mRNA Levels of the Leptin Receptor Subtypes in the Hypothalamus During Pregnancy and Lactation1Biology of Reproduction, 2000
- The Placenta Is Not the Main Source of Leptin Production in Pregnant Rat: Gestational Profile of Leptin in Plasma and Adipose TissuesBiochemical and Biophysical Research Communications, 1997
- Identification of targets of leptin action in rat hypothalamus.JCI Insight, 1996
- Localization of leptin receptor mRNA and the long form splice variant (Ob‐Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridizationFEBS Letters, 1996
- Some effects of ovarian hormones on food intake and body weight in female rats.Journal of Comparative and Physiological Psychology, 1975
- THE EFFECTS OF PROGESTERONE ON BODY WEIGHT AND COMPOSITION IN THE RATJournal of Endocrinology, 1967