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Fat Preference: A Novel Model of Eating Behavior in Rats
Published on: June 27, 2014
Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming
Dan Zhou1, Huan Wang1, Hemiao Cui1
1Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801.
Insights
Maternal high-fat diet alters gene expression and histone modifications in adult female offspring, leading to increased liver fat. These changes in phosphoenolpyruvate carboxykinase (PEPCK) and fatty acid synthase (FASN) are gender-specific.
Area of Science:
- Metabolism and Endocrinology
- Epigenetics
- Developmental Biology
Background:
- Maternal high-fat diet during pregnancy can affect offspring's metabolic health.
- Previous studies showed PEPCK gene expression and histone modifications in neonatal rats exposed to a high-fat diet in utero.
- The persistence of these epigenetic changes into adulthood was unknown.
Purpose of the Study:
- To investigate if gestational high-fat diet-induced alterations in hepatic PEPCK gene expression and histone modifications persist in adult offspring.
- To examine gender-specific effects of maternal high-fat diet on metabolic parameters and gene expression in adult offspring.
Main Methods:
- Rat dams were fed control or high-fat diets during gestation and lactation.
- Offspring were weaned onto a control diet.
- Liver tissues were collected from 12-week-old offspring (C/C and HF/C groups) for analysis of NADH levels, gene expression (PEPCK, FASN), and histone modifications (H3K4me2, H3ac, H3K4me3, H3K9me3).
Main Results:
- Adult female offspring from the HF/C group showed increased hepatic NADH levels and fat accumulation.
- PEPCK and FASN mRNA expression were significantly increased in the livers of female offspring in the HF/C group.
- Specific histone modifications, including increased H3K4me2, H3ac, and H3K4me3, and decreased H3K9me3 at the PEPCK gene promoter, were observed in female offspring from the HF/C group.
Conclusions:
- Maternal high-fat diet can program persistent PEPCK gene expression in adult female offspring via epigenetic modifications.
- Induced PEPCK expression, along with increased FASN and NADH levels, may contribute to gender-specific fat deposition in adult offspring.
- These findings highlight the long-term, gender-specific metabolic consequences of maternal dietary habits.
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.
