Long-term hypoxia modulates expression of key genes regulating adipose function in the late-gestation ovine fetus

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2008-04, Vol.294 (4), p.R1312-R1318
• Main Authors: Myers, Dean A, Hanson, Krista, Mlynarczyk, Malgorzata, Kaushal, Kanchan M, Ducsay, Charles A
• Format: Article
• Language: English
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 1 - genetics; 11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism; Abdominal Fat - metabolism; Acclimatization; Altitude; Animals; Female; Fetus - metabolism; Fetuses; Gene expression; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Genes; Gestational Age; Hormones; Hydrocortisone - metabolism; Hypoxia; Hypoxia - genetics; Hypoxia - metabolism; Iodide Peroxidase - genetics; Iodide Peroxidase - metabolism; Iodothyronine Deiodinase Type II; Ion Channels - genetics; Ion Channels - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; PPAR alpha - genetics; PPAR alpha - metabolism; PPAR gamma - genetics; PPAR gamma - metabolism; Pregnancy; Proteins; Receptors, Adrenergic, beta-3 - genetics; Receptors, Adrenergic, beta-3 - metabolism; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; RNA, Messenger - metabolism; Sheep; Thermogenesis - genetics; Time Factors; Uncoupling Protein 1; Uncoupling Protein 2
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00004.2008

1 Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and 2 Center for Perinatal Biology, Loma Linda University, School of Medicine, Loma Linda, California Submitted 3 January 2008 ; accepted in final form 17 February 2008 A major function of abdominal adipose in the newborn is nonshivering thermogenesis. Uncoupling protein (UCP) UCP1 and UCP2 play major roles in thermogenesis. The present study tested the hypothesis that long-term hypoxia (LTH) modulates expression of UCP1 and UCP2, and key genes regulating expression of these genes in the late-gestation ovine fetus. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dG); perirenal adipose tissue was collected from LTH and age-matched, normoxic control fetuses at 139–141 dG. Quantitative real-time PCR was used to analyze mRNA for UCP1, UCP2, 11β hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2 (HSD11B2), glucocorticoid receptor (GR), β3 adrenergic receptor (β3AR), deiodinase type 1 (DIO1) and DIO2, peroxisome proliferator activated receptor (PPAR) and and PPAR coactivator 1 (PGC1 ). Concentrations of mRNA for UCP1, HSD11B1, PPAR , PGC1, DIO1, and DIO2 were significantly higher in perirenal adipose of LTH compared with control fetuses, while mRNA for HSD11B2, GR, or PPAR in perirenal adipose did not differ between control and LTH fetuses. The increased expression of UCP1 is likely an adaptive response to LTH, assuring adequate thermogenesis in the event of birth under oxygen-limiting conditions. Because both glucocorticoids and thyroid hormone regulate UCP1 expression, the increase in HSD11B1, DIO1, and DIO2 implicate increased adipose capacity for local synthesis of these hormones. PPAR and its coactivator may provide an underlying mechanism via which LTH alters development of the fetal adipocyte. These findings have important implications regarding fetal/neonatal adipose tissue function in response to LTH. uncoupling protein; cortisol Address for reprint requests and other correspondence: D. A. Myers, Dept. of Obstetrics and Gynecology, Univ. of Oklahoma Health Sciences Center, Suíte 468, RP1, 800 Research Parkway, Oklahoma City, OK 73104 (e-mail: dean-myers{at}ouhsc.edu )