TY - JOUR
T1 - Epigenomics
T2 - Maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates
AU - Suter, Melissa
AU - Bocock, Philip
AU - Showalter, Lori
AU - Hu, Min
AU - Shope, Cynthia
AU - McKnight, Robert
AU - Grove, Kevin
AU - Lane, Robert
AU - Aagaard-Tillery, Kjersti
PY - 2011/2
Y1 - 2011/2
N2 - The effect of in utero exposure to a maternal high-fat diet on the peripheral circadian system of the fetus is unknown. Using mRNA copy number analysis, we report that the components of the peripheral circadian machinery are transcribed in the nonhuman primate fetal liver in an intact phase-antiphase fashion and that Npas2, a paralog of the Clock transcription factor, serves as the rate-limiting transcript by virtue of its relative low abundance (10- to 1000-fold lower). We show that exposure to a maternal high-fat diet in utero significantly alters the expression of fetal hepatic Npas2 (up to 7.1-fold, P<0.001) compared with that in control diet-exposed animals and is reversible in fetal offspring from obese dams reversed to a control diet (1.3-fold, P>0.05). Although the Npas2 promoter remains largely unmethylated, differential Npas2 promoter occupancy of acetylation of fetal histone H3 at lysine 14 (H3K14ac) occurs in response to maternal high-fat diet exposure compared with control diet-exposed animals. Furthermore, we find that disruption of Npas2 is consistent with high-fat diet exposure in juvenile animals, regardless of in utero diet exposure. In summary, the data suggest that peripheral Npas2 expression is uniquely vulnerable to diet exposure.
AB - The effect of in utero exposure to a maternal high-fat diet on the peripheral circadian system of the fetus is unknown. Using mRNA copy number analysis, we report that the components of the peripheral circadian machinery are transcribed in the nonhuman primate fetal liver in an intact phase-antiphase fashion and that Npas2, a paralog of the Clock transcription factor, serves as the rate-limiting transcript by virtue of its relative low abundance (10- to 1000-fold lower). We show that exposure to a maternal high-fat diet in utero significantly alters the expression of fetal hepatic Npas2 (up to 7.1-fold, P<0.001) compared with that in control diet-exposed animals and is reversible in fetal offspring from obese dams reversed to a control diet (1.3-fold, P>0.05). Although the Npas2 promoter remains largely unmethylated, differential Npas2 promoter occupancy of acetylation of fetal histone H3 at lysine 14 (H3K14ac) occurs in response to maternal high-fat diet exposure compared with control diet-exposed animals. Furthermore, we find that disruption of Npas2 is consistent with high-fat diet exposure in juvenile animals, regardless of in utero diet exposure. In summary, the data suggest that peripheral Npas2 expression is uniquely vulnerable to diet exposure.
KW - Epigenetics
KW - Fetal origins of adult disease
KW - Npas2
UR - http://www.scopus.com/inward/record.url?scp=79551627622&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551627622&partnerID=8YFLogxK
U2 - 10.1096/fj.10-172080
DO - 10.1096/fj.10-172080
M3 - Article
C2 - 21097519
AN - SCOPUS:79551627622
SN - 0892-6638
VL - 25
SP - 714
EP - 726
JO - FASEB Journal
JF - FASEB Journal
IS - 2
ER -