The regulation of hepatic Pon1 by a maternal high-fat diet is gender specific and may occur through promoter histone modifications in neonatal rats.
The antioxidant (AOX) defense system is critical for combating whole-body oxidative stress, and the present study aimed to determine the consequences of a maternal high-fat (HF) diet on neonatal hepatic lipid accumulation, oxidative stress, the expression of AOX genes, as well as epigenetic histone modifications within Pon1, an AOX enzyme. Hepatic thiobarbituric acid reactive substances were significantly increased and nonesterified fatty acids decreased in offspring of HF-fed dams, while triglycerides increased in male but not female HF offspring when compared to controls (C). Pon1, Pon2, Pon3 and Sod2 were significantly increased in offspring of HF-fed dams when compared to C. However, the increase in Pon1 and Pon3 was only significant in male but not female offspring. When compared to C, the hepatic Pon1 promoter of male and female HF offspring had significantly more acetylated histone H4 as well as dimethylated histone H3 at lysine residue 4, which are both involved in transcriptional activation. Trimethylation of histone H3 at lysine residue 9, which is involved in transcriptional repression, was only associated with genes in females. Results from the present study reveal that a maternal HF diet affects hepatic metabolism in the neonate in a gender-specific manner, and these differences, in association with epigenetic modification of histones, may contribute to the known gender differences in oxidative balance.
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Rita S
RS
Strakovsky
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Xiyuan
X
Zhang
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Dan
D
Zhou
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. Electronic address: yxpan@illinois.edu.
Yuan-Xiang
YX
Pan
D000818:Animals; D000831:Animals, Newborn; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D059305:Diet, High-Fat; D005260:Female; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015533:Transcriptional Activation
D017931:DNA Primers; D006657:Histones; C572204:Pon1 protein, rat; D043303:Aryldialkylphosphatase
AOX; Developmental programming; Epigenetics; H3Ac; H3K4Me2; H3K9Me3; H4Ac; HF; In uterine; Oxidative stress; PON; SOD; acetylated histone H3; acetylated histone H4; antioxidant; dimethylation of histone H3 at lysine residue 4; high fat; paraoxonase; superoxide dismutase; trimethylation of histone H3 at lysine residue 9