Perinatal Exposure to a High-Fat Diet Is Associated with Reduced Hepatic Sympathetic Innervation in One-Year Old Male Japanese Macaques

Wilmon F. Grant, Lindsey E. Nicol, Stephanie R. Thorn, Kevin Grove, Jacob E. Friedman, Daniel Marks

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere48119
JournalPLoS One
Volume7
Issue number10
DOIs
StatePublished - Oct 30 2012

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Macaca fuscata
Macaca
High Fat Diet
high fat diet
innervation
Nutrition
Fats
liver
Liver
apoptosis
Apoptosis
inflammation
Animals
Inflammation
Adrenergic Fibers
neurodevelopment
cholinergic agents
fatty liver
postpartum period
nerve fibers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Perinatal Exposure to a High-Fat Diet Is Associated with Reduced Hepatic Sympathetic Innervation in One-Year Old Male Japanese Macaques. / Grant, Wilmon F.; Nicol, Lindsey E.; Thorn, Stephanie R.; Grove, Kevin; Friedman, Jacob E.; Marks, Daniel.

In: PLoS One, Vol. 7, No. 10, e48119, 30.10.2012.

Research output: Contribution to journalArticle

Grant, Wilmon F. ; Nicol, Lindsey E. ; Thorn, Stephanie R. ; Grove, Kevin ; Friedman, Jacob E. ; Marks, Daniel. / Perinatal Exposure to a High-Fat Diet Is Associated with Reduced Hepatic Sympathetic Innervation in One-Year Old Male Japanese Macaques. In: PLoS One. 2012 ; Vol. 7, No. 10.
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