5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

Disease Models & Mechanisms
M S Martin-GronertS E Ozanne

Abstract

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite...Continue Reading

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Citations

Oct 14, 2016·Disease Models & Mechanisms·Tim AitmanAron M Geurts
Feb 6, 2018·Neurochemical Research·Irina V RomanovaAlexander O Shpakov
Dec 23, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Richard M Sharpe
Aug 30, 2018·PloS One·Daniel E FelsingKathryn A Cunningham
Feb 23, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Gabriel Araújo TavaresSandra Lopes de Souza
Jul 29, 2020·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Edward T WargentClaire J Stocker
Aug 23, 2020·International Journal of Molecular Sciences·Sabrina I HanswijkJudith R Homberg
Dec 26, 2018·Frontiers in Pharmacology·Amanda E PriceKathryn A Cunningham

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Methods Mentioned

BETA
laser-capture microdissection
dissection
chip
PCR
in vitro transcription

Software Mentioned

UniGene
RMA
Ingenuity Pathway analysis
GeneChip
Image Proplus
GeneSpring GX
Affymetrix GeneChip Operating Software
GeneChip operating software ( GCOS )
GCOS

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