Perinatal exposure to a high-fat diet is associated with reduced hepatic sympathetic innervation in one-year old male Japanese macaques

PLoS One. 2012;7(10):e48119. doi: 10.1371/journal.pone.0048119. Epub 2012 Oct 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Glucose Transporter Type 2 / genetics
  • Glucose Transporter Type 2 / metabolism
  • Glycogen / metabolism
  • Hepatitis / etiology
  • Hepatitis / metabolism
  • Hepatitis / pathology
  • Inflammation Mediators / metabolism
  • Liver / embryology
  • Liver / growth & development
  • Liver / innervation*
  • Liver / metabolism
  • Macaca
  • Male
  • Maternal-Fetal Exchange
  • Neuropeptide Y / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / pathology
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism
  • Sympathetic Fibers, Postganglionic / metabolism
  • Sympathetic Fibers, Postganglionic / pathology
  • Sympathetic Nervous System / embryology*
  • Sympathetic Nervous System / growth & development
  • Sympathetic Nervous System / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Cytokines
  • Glucose Transporter Type 2
  • Inflammation Mediators
  • Neuropeptide Y
  • Receptors, Neuropeptide Y
  • Receptors, Nicotinic
  • Glycogen
  • Tyrosine 3-Monooxygenase