Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming Pepck expression

Dan Zhou, Huan Wang, Hemiao Cui, Hong Chen, Yuan-Xiang Pan

Research output: Contribution to journalArticle

Abstract

Phosphoenolpyruvate carboxykinase (PEPCK) produces phosphoenolpyruvate during glyceroneogenesis. We previously demonstrated that a high-fat diet during pregnancy induced Pepck mRNA expression in neonatal rat pups, which is characterized by histone modifications in specific regions of the gene (Strakovsky RS, Zhang X, Zhou D, Pan YX. Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats. The Journal of Physiology 2011;589:2707-17). In the present study, we investigated whether these alterations persistent in adult offspring. Dams were fed either control or high-fat diet throughout gestation and lactation. Offspring were placed on control diet after weaning, generating C/C and HF/C groups. Liver was collected at 12 weeks of age. Hepatic nicotinamide adenine dinucleotide (reduced) (NADH) level was increased in both genders, but fat accumulation occurred only in liver of female offspring in HF/C group. This was accompanied by a significant increase of Pepck and fatty acid synthase (. Fasn) mRNA expression in only female liver. The induction of Pepck gene expression in females was associated with increased dimethylated histone H3 lysine 4 level in multiple regions of the gene. Meanwhile, acetylated histone H3 and trimethylated histone H3 lysine 4 were induced at a specific coding region in HF/C, accompanied by decreased trimethylated histone H3 lysine 9 level at the promoter of female offspring. In conclusion, maternal high-fat diet programs Pepck expression through histone modifications in adult female offspring. Persistent Pepck induction in females may contribute to increased triglyceride synthesis, together with induced Fasn expression and NADH levels, which may lead to increased fat deposition in a gender-specific manner.

Original languageEnglish (US)
Pages (from-to)433-440
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume26
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

High Fat Diet
Nutrition
Histones
Rats
Histone Code
Fats
Phosphoenolpyruvate
Liver
NAD
Lysine
Gene expression
Genes
Gene Expression
Fatty Acid Synthases
Pregnancy
Messenger RNA
Weaning
Lactation
Physiology
Triglycerides

Keywords

  • Epigenetic modification
  • Fatty liver
  • Glyceroneogenesis
  • Maternal programming
  • PEPCK

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming Pepck expression. / Zhou, Dan; Wang, Huan; Cui, Hemiao; Chen, Hong; Pan, Yuan-Xiang.

In: Journal of Nutritional Biochemistry, Vol. 26, No. 5, 01.05.2015, p. 433-440.

Research output: Contribution to journalArticle

@article{218793f11dae421684ac71e14af0d1d0,
title = "Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming Pepck expression",
abstract = "Phosphoenolpyruvate carboxykinase (PEPCK) produces phosphoenolpyruvate during glyceroneogenesis. We previously demonstrated that a high-fat diet during pregnancy induced Pepck mRNA expression in neonatal rat pups, which is characterized by histone modifications in specific regions of the gene (Strakovsky RS, Zhang X, Zhou D, Pan YX. Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats. The Journal of Physiology 2011;589:2707-17). In the present study, we investigated whether these alterations persistent in adult offspring. Dams were fed either control or high-fat diet throughout gestation and lactation. Offspring were placed on control diet after weaning, generating C/C and HF/C groups. Liver was collected at 12 weeks of age. Hepatic nicotinamide adenine dinucleotide (reduced) (NADH) level was increased in both genders, but fat accumulation occurred only in liver of female offspring in HF/C group. This was accompanied by a significant increase of Pepck and fatty acid synthase (. Fasn) mRNA expression in only female liver. The induction of Pepck gene expression in females was associated with increased dimethylated histone H3 lysine 4 level in multiple regions of the gene. Meanwhile, acetylated histone H3 and trimethylated histone H3 lysine 4 were induced at a specific coding region in HF/C, accompanied by decreased trimethylated histone H3 lysine 9 level at the promoter of female offspring. In conclusion, maternal high-fat diet programs Pepck expression through histone modifications in adult female offspring. Persistent Pepck induction in females may contribute to increased triglyceride synthesis, together with induced Fasn expression and NADH levels, which may lead to increased fat deposition in a gender-specific manner.",
keywords = "Epigenetic modification, Fatty liver, Glyceroneogenesis, Maternal programming, PEPCK",
author = "Dan Zhou and Huan Wang and Hemiao Cui and Hong Chen and Yuan-Xiang Pan",
year = "2015",
month = "5",
day = "1",
doi = "10.1016/j.jnutbio.2014.10.009",
language = "English (US)",
volume = "26",
pages = "433--440",
journal = "Journal of Nutritional Biochemistry",
issn = "0955-2863",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming Pepck expression

AU - Zhou, Dan

AU - Wang, Huan

AU - Cui, Hemiao

AU - Chen, Hong

AU - Pan, Yuan-Xiang

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Phosphoenolpyruvate carboxykinase (PEPCK) produces phosphoenolpyruvate during glyceroneogenesis. We previously demonstrated that a high-fat diet during pregnancy induced Pepck mRNA expression in neonatal rat pups, which is characterized by histone modifications in specific regions of the gene (Strakovsky RS, Zhang X, Zhou D, Pan YX. Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats. The Journal of Physiology 2011;589:2707-17). In the present study, we investigated whether these alterations persistent in adult offspring. Dams were fed either control or high-fat diet throughout gestation and lactation. Offspring were placed on control diet after weaning, generating C/C and HF/C groups. Liver was collected at 12 weeks of age. Hepatic nicotinamide adenine dinucleotide (reduced) (NADH) level was increased in both genders, but fat accumulation occurred only in liver of female offspring in HF/C group. This was accompanied by a significant increase of Pepck and fatty acid synthase (. Fasn) mRNA expression in only female liver. The induction of Pepck gene expression in females was associated with increased dimethylated histone H3 lysine 4 level in multiple regions of the gene. Meanwhile, acetylated histone H3 and trimethylated histone H3 lysine 4 were induced at a specific coding region in HF/C, accompanied by decreased trimethylated histone H3 lysine 9 level at the promoter of female offspring. In conclusion, maternal high-fat diet programs Pepck expression through histone modifications in adult female offspring. Persistent Pepck induction in females may contribute to increased triglyceride synthesis, together with induced Fasn expression and NADH levels, which may lead to increased fat deposition in a gender-specific manner.

AB - Phosphoenolpyruvate carboxykinase (PEPCK) produces phosphoenolpyruvate during glyceroneogenesis. We previously demonstrated that a high-fat diet during pregnancy induced Pepck mRNA expression in neonatal rat pups, which is characterized by histone modifications in specific regions of the gene (Strakovsky RS, Zhang X, Zhou D, Pan YX. Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats. The Journal of Physiology 2011;589:2707-17). In the present study, we investigated whether these alterations persistent in adult offspring. Dams were fed either control or high-fat diet throughout gestation and lactation. Offspring were placed on control diet after weaning, generating C/C and HF/C groups. Liver was collected at 12 weeks of age. Hepatic nicotinamide adenine dinucleotide (reduced) (NADH) level was increased in both genders, but fat accumulation occurred only in liver of female offspring in HF/C group. This was accompanied by a significant increase of Pepck and fatty acid synthase (. Fasn) mRNA expression in only female liver. The induction of Pepck gene expression in females was associated with increased dimethylated histone H3 lysine 4 level in multiple regions of the gene. Meanwhile, acetylated histone H3 and trimethylated histone H3 lysine 4 were induced at a specific coding region in HF/C, accompanied by decreased trimethylated histone H3 lysine 9 level at the promoter of female offspring. In conclusion, maternal high-fat diet programs Pepck expression through histone modifications in adult female offspring. Persistent Pepck induction in females may contribute to increased triglyceride synthesis, together with induced Fasn expression and NADH levels, which may lead to increased fat deposition in a gender-specific manner.

KW - Epigenetic modification

KW - Fatty liver

KW - Glyceroneogenesis

KW - Maternal programming

KW - PEPCK

UR - http://www.scopus.com/inward/record.url?scp=84928288784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928288784&partnerID=8YFLogxK

U2 - 10.1016/j.jnutbio.2014.10.009

DO - 10.1016/j.jnutbio.2014.10.009

M3 - Article

C2 - 25716581

AN - SCOPUS:84928288784

VL - 26

SP - 433

EP - 440

JO - Journal of Nutritional Biochemistry

JF - Journal of Nutritional Biochemistry

SN - 0955-2863

IS - 5

ER -