| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 2, 2003
Accepted on August 20, 2003
1 Division of Endocrinology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Québec, Canada H3T 1E2, Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, and CREST of Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
* To whom correspondence should be addressed. E-mail: enrique.silva{at}staff.mcgill.ca.
A role for the mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) in thermogenesis was investigated in transgenic mice lacking the mGPD gene (mGPD-). Reared and studied at 22 C, these mice have a small but significant reduction (7-10%) in energy expenditure, as evidenced by oxygen consumption (QO2) and food intake, and show signs of increased brown adipose tissue (BAT) stimulation, higher plasma T4 and T3 concentrations as well as increased UCP3 expression in muscle. When acclimated at thermoneutrality temperature (32 C), QO2 decreased in both genotypes but the difference between them widened to 16%, while BAT underwent atrophy and plasma T4, T3 levels and UCP3 mRNA decreased, yet T3 and UCP3 persisted significantly higher in mGPD- mice. Such differences disappeared when the mice were rendered hypothyroid. A compensatory role for the observed changes in BAT, thyroid hormone levels and UCP3 was investigated with a 2-hour cold challenge of 12 C in euthyroid and hypothyroid mice. No hypothermia ensued if the mice had been acclimated at 22 C, but when acclimated at 32 C, euthyroid mGPD- mice became significantly more hypothermic than the WT controls. When rendered hypothyroid, this difference was accentuated and the mGPD- mice developed profound hypothermia (
28 C vs. 34 C in WT; P < 0.001). Thus, mGPD deficient mice have, in spite of increased plasma T4 and T3, a small but distinct reduction in obligatory thermogenesis, which is compensated by increased BAT facultative thermogenesis and by thyroid hormone-dependent mechanisms using other proteins, possibly UCP3. The results support a role for mGPD in thyroid hormone thermogenesis.
This article has been cited by other articles:
 |
|
 |
|
  S C P Dutra, E G Moura, A L Rodrigues, P C Lisboa, I Bonomo, F P Toste, and M C F Passos Cold exposure restores the decrease in leptin receptors (OB-Rb) caused by neonatal leptin treatment in 30-day-old rats J. Endocrinol., November 1, 2007; 195(2): 351 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Silva Thermogenic Mechanisms and Their Hormonal Regulation Physiol Rev, April 1, 2006; 86(2): 435 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Marrif, A. Schifman, Z. Stepanyan, M.-A. Gillis, A. Calderone, R. E. Weiss, J. Samarut, and J. E. Silva Temperature Homeostasis in Transgenic Mice Lacking Thyroid Hormone Receptor-{alpha} Gene Products Endocrinology, July 1, 2005; 146(7): 2872 - 2884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Alfadda, R. A. DosSantos, Z. Stepanyan, H. Marrif, and J. E. Silva Mice with deletion of the mitochondrial glycerol-3-phosphate dehydrogenase gene exhibit a thrifty phenotype: effect of gender Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R147 - R156. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
