title: Prenatal fat-rich diet exposure alters responses of embryonic neurons to the chemokine, CCL2, in the hypothalamus.
abstract: Maternal consumption of a high-fat diet (HFD) during pregnancy is found to stimulate the genesis of hypothalamic orexigenic peptide neurons in the offspring, while HFD intake in adult animals produces a systemic low-grade inflammation which increases neuroimmune factors that may affect neurogenesis and neuronal migration. Building on this evidence and our recent study showing that the inflammatory chemokine, CCL2, stimulates the migration of hypothalamic neurons and expression of orexigenic neuropeptides, we tested here the possibility that prenatal exposure to a HFD in rats affects this chemokine system, both CCL2 and its receptors, CCR2 and CCR4, and alters its actions on hypothalamic neurons, specifically those expressing the neuropeptides, enkephalin (ENK) and galanin (GAL). Using primary dissociated hypothalamic neurons extracted from embryos on embryonic day 19, we found that prenatal HFD exposure compared to chow control actually reduces the expression of CCL2 in these hypothalamic neurons, while increasing CCR2 and CCR4 expression, and also reduces the sensitivity of hypothalamic neurons to CCL2. The HFD abolished the dose-dependent, stimulatory effect of CCL2 on the number of migrated neurons and even shifted its normal stimulatory effect on migrational velocity and distance traveled by control neurons to an inhibition of migration. Further, it abolished the dose-dependent, stimulatory effect of CCL2 on neuronal expression of ENK and GAL. These results demonstrate that prenatal HFD exposure greatly disturbs the functioning of the CCL2 chemokine system in embryonic hypothalamic neurons, reducing its endogenous levels and ability to promote the migration of neurons and their expression of orexigenic peptides.
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: kpoon@rockefeller.edu.
authors.forename: K
authors.initials: K
authors.lastname: Poon
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: Jamiex250@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Abramova
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: hth2101@gmail.com.
authors.forename: H T
authors.initials: HT
authors.lastname: Ho
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: leibow@rockefeller.edu.
authors.forename: S
authors.initials: S
authors.lastname: Leibowitz
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D019004:Galanin / Q000378:metabolism; D007031:Hypothalamus / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; C515356:Ccr4 protein, rat; D018932:Chemokine CCL2; D004041:Dietary Fats; D004745:Enkephalins; C489169:Gal protein, rat; D011498:Protein Precursors; D012333:RNA, Messenger; D054390:Receptors, CCR2; D054398:Receptors, CCR4; D019004:Galanin
keywords: C–C chemokine ligand 2 (CCL2); enkephalin; galanin; hypothalamus; migration; prenatal high-fat diet