title: Prenatal fat exposure and hypothalamic PPAR β/δ: Possible relationship to increased neurogenesis of orexigenic peptide neurons.
abstract: Gestational exposure to a fat-rich diet, while elevating maternal circulating fatty acids, increases in the offspring's hypothalamus and amygdala the proliferation and density of neurons that express neuropeptides known to stimulate consummatory behavior. To understand the relationship between these phenomena, this study examined in the brain of postnatal offspring (day 15) the effect of prenatal fat exposure on the transcription factor, peroxisome proliferator-activated receptor (PPAR) β/δ, which is sensitive to fatty acids, and the relationship of PPAR β/δ to the orexigenic neuropeptides, orexin, melanin-concentrating hormone, and enkephalin. Prenatal exposure to a fat-rich diet compared to low-fat chow increased the density of cells immunoreactive for PPAR β/δ in the hypothalamic paraventricular nucleus (PVN), perifornical lateral hypothalamus (PFLH), and central nucleus of the amygdala (CeA), but not the hypothalamic arcuate nucleus or basolateral amygdaloid nucleus. It also increased co-labeling of PPAR β/δ with the cell proliferation marker, BrdU, or neuronal marker, NeuN, and the triple labeling of PPAR β/δ with BrdU plus NeuN, indicating an increase in proliferation and density of new PPAR β/δ neurons. Prenatal fat exposure stimulated the double-labeling of PPAR β/δ with orexin or melanin-concentrating hormone in the PFLH and enkephalin in the PVN and CeA and also triple-labeling of PPAR β/δ with BrdU and these neuropeptides, indicating that dietary fat increases the genesis of PPAR β/δ neurons that produce these peptides. These findings demonstrate a close anatomical relationship between PPAR β/δ and the increased proliferation and density of peptide-expressing neurons in the hypothalamus and amygdala of fat-exposed offspring.
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Chang
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: O
authors.initials: O
authors.lastname: Karatayev
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: O
authors.initials: O
authors.lastname: Lukatskaya
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA. Electronic address: leibow@rockefeller.edu.
authors.forename: S F
authors.initials: SF
authors.lastname: Leibowitz
mesh_terms: D000679:Amygdala; D000818:Animals; D003259:Consummatory Behavior; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology*; D004198:Disease Susceptibility / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology; D008543:Melanins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D047494:PPAR delta / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D004745:Enkephalins; D007028:Hypothalamic Hormones; D008543:Melanins; D047494:PPAR delta; D048068:PPAR-beta; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone
keywords: Amygdala; Hypothalamus; Melanin-concentrating hormone, Enkephalin; Orexin; Peroxisome proliferator-activated receptor (PPAR); Prenatal fat; Proliferation; β/δ