title: Perinatal exposure to a high-fat diet is associated with reduced hepatic sympathetic innervation in one-year old male Japanese macaques.
abstract: Our group recently demonstrated that maternal high-fat diet (HFD) consumption is associated with non-alcoholic fatty liver disease, increased apoptosis, and changes in gluconeogenic gene expression and chromatin structure in fetal nonhuman primate (NHP) liver. However, little is known about the long-term effects that a HFD has on hepatic nervous system development in offspring, a system that plays an important role in regulating hepatic metabolism. Utilizing immunohistochemistry and Real-Time PCR, we quantified sympathetic nerve fiber density, apoptosis, inflammation, and other autonomic components in the livers of fetal and one-year old Japanese macaques chronically exposed to a HFD. We found that HFD exposure in-utero and throughout the postnatal period (HFD/HFD), when compared to animals receiving a CTR diet for the same developmental period (CTR/CTR), is associated with a 1.7 fold decrease in periportal sympathetic innervation, a 5 fold decrease in parenchymal sympathetic innervation, and a 2.5 fold increase in hepatic apoptosis in the livers of one-year old male animals. Additionally, we observed an increase in hepatic inflammation and a decrease in a key component of the cholinergic anti-inflammatory pathway in one-year old HFD/HFD offspring. Taken together, these findings reinforce the impact that continuous exposure to a HFD has in the development of long-term hepatic pathologies in offspring and highlights a potential neuroanatomical basis for hepatic metabolic dysfunction.
authors.affiliation: Neuroscience Graduate Program, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Wilmon F
authors.initials: WF
authors.lastname: Grant
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Nicol
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Thorn
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Friedman
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Marks
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000294:innervation* / Q000378:metabolism; D008251:Macaca; D008297:Male; D008431:Maternal-Fetal Exchange; D009478:Neuropeptide Y / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D017779:Sympathetic Fibers, Postganglionic / Q000378:metabolism / Q000473:pathology; D013564:Sympathetic Nervous System / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D016207:Cytokines; D051273:Glucose Transporter Type 2; D018836:Inflammation Mediators; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D011978:Receptors, Nicotinic; D006003:Glycogen; D014446:Tyrosine 3-Monooxygenase