Full Expression of Uncoupling Protein Gene Requires the Concurrence of Norepinephrine and Triiodothyronine
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We have examined the uncoupling (UCP) protein gene expression in euthyroid and hypothyroid rats. UCP mRNA levels were estimated by northern blot analysis of total RNA from brown adipose tissue (BAT). Stimuli were endogenous (cold) and exogenous norepinephrine (NE), isoproterenol, T3, and T4. While in euthyroid rats UCP mRNA levels increase 2- to 3-fold by 2 h after NE or overnight cold exposure, these stimuli and isoproterenol are ineffective in hypothyroid rats. One single dose of T4, equal to the daily production rate, brings about a normal response in hypothyroid rats exposed to cold overnight. Hypothyroid rats recover their responsiveness to NE approximately 4 h after a receptor saturating dose of T3. On the other hand, such a dose of T3 induces a 3- to 4-fold increase in UCP mRNA levels in hypothyroid rats without the need of exogenous NE, and this response is not reduced by raising ambient temperature to thermoneutrality (28 C). However, the following evidence indicates that T3 requires adrenergic input to stimulate the accumulation of UCP mRNA: first, euthyroid animals maintained at 28 C do not respond to such a treatment. Second, when T3 was injected to hypothyroid rats with unilaterally denervated BAT, only the intact side responded to T3 with an elevation of the UCP mRNA levels, but both sides remained responsive to T3 + NE. We conclude that: 1) the failure of UCP mRNA to increase in response to cold is due to an intrinsic defect in BAT to respond to NE; 2) T3 cannot induce gene in the absence of adrenergic input; and 3) the full expression of UCP gene requires both adrenergic- and T3-dependent signals. In addition, the data are consistent with reports indicating an elevated sympathetic tone on BAT in hypothyroidism and, further, suggest that thermal stress is not the only cause for the enhanced sympathetic activity in this condition.
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Catecholamines such as noradrenaline activate β3 adrenergic receptors and upregulate UCP-1 expression in mouse, rat, and human brown adipose tissues.
“These molecules are also known to upregulate UCP-1 expression in many models, including mouse [40,41], rat [42,43], and human [44] brown adipose tissues.”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [42]
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Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular Cloning. A Laboratory Manual
Wood, E. (1983) · Biochemical Education · doi:10.1016/0307-4412(83)90068-7 · Cited by 29,534 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
Feinberg, A. P., & Vogelstein, B. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90418-9 · Cited by 24,512 · see citing works
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
Chirgwin, J. M., Przybyla, A., MacDonald, R. J., & Rutter, W. J. (1979) · Biochemistry · doi:10.1021/bi00591a005 · Cited by 21,725 · see citing works
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
(1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90381-6 · Cited by 4,950 · see citing works
Basic Methods in Molecular Biology
(1986) · Elsevier eBooks · doi:10.1016/b978-0-444-01082-7.x5001-2 · Cited by 3,163 · see citing works
Thermogenic mechanisms in brown fat.
Nicholls, D. G., & Locke, R. M. (1984) · Physiological Reviews · doi:10.1152/physrev.1984.64.1.1 · Cited by 1,602 · see citing works
Advances in Our Understanding of Thyroid Hormone Action at the Cellular Level*
Oppenheimer, J. H., Schwartz, H. L., Mariash, C. N., Kinlaw, W. B., Wong, N. C. W., & Freake, H. C. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-3-288 · Cited by 476 · see citing works
Basic methods in molecular biology
Howe, C. J. (1987) · Trends in Genetics · doi:10.1016/0168-9525(87)90245-9 · Cited by 436 · see citing works
Adrenergic activation of triiodothyronine production in brown adipose tissue
Silva, J. E., & Larsen, P. R. (1983) · Nature · doi:10.1038/305712a0 · Cited by 401 · see citing works
Self-citationBianco, A. C., & Silva, J. E. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112798 · Cited by 347 · see citing works
Self-citationBouillaud, F., Ricquier, D., Thibault, J., & Weissenbach, J. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.2.445 · Cited by 244 · see citing works
Brown Adipose Tissue Metabolism and Thermogenesis
Himms‐Hagen, J. (1985) · Annual Review of Nutrition · doi:10.1146/annurev.nu.05.070185.000441 · Cited by 224 · see citing works
THYROXINE 5′-DEIODINASE ACTIVITY IN BROWN ADIPOSE TISSUE
Leonard, J. L., MELLEN, S. A., & LARSEN, R. P. (1983) · Endocrinology · doi:10.1210/endo-112-3-1153 · Cited by 213 · see citing works
Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine
Diamond, D. J., & Goodman, H. M. (1985) · Journal of Molecular Biology · doi:10.1016/0022-2836(85)90323-7 · Cited by 167 · see citing works
Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation
Bianco, A. C., & Silva, J. E. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.253.3.e255 · Cited by 109 · see citing works
Self-citationRole of thyroid hormone in cold-induced changes in rat brown adipose tissue mitochondria
Triandafillou, J., Gwilliam, C., & Himms‐Hagen, J. (1982) · Canadian Journal of Biochemistry · doi:10.1139/o82-065 · Cited by 96 · see citing works
Carneheim, C., Nedergaard, J., & Cannon, B. (1984) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1984.246.4.e327 · Cited by 96 · see citing works
Stabilization of a Specific Nuclear mRNA Precursor by Thyroid Hormone
Narayan, P., & Towle, H. C. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2642-2646.1985 · Cited by 95 · see citing works
Ridley, R. G., Patel, H. V., Gerber, G. E., Morton, R. C., & Freeman, K. B. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.10.4025 · Cited by 85 · see citing works
Rothwell, N. J., & Stock, M. J. (1984) · The Journal of Physiology · doi:10.1113/jphysiol.1984.sp015431 · Cited by 73 · see citing works
Dozin, B., Rall, J. E., & Nikodem, V. M. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4705 · Cited by 62 · see citing works
Unilaterality of the sympathetic innervation of each pad of rat interscapular brown adipose tissue
Foster, D. O., Depocas, F., & Behrens, G. Z. (1982) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y82-018 · Cited by 62 · see citing works
Thyroid-catecholamine interactions in isolated rat brown adipocytes
Sundin, U., Mills, I., & Fain, J. N. (1984) · Metabolism · doi:10.1016/0026-0495(84)90232-4 · Cited by 56 · see citing works
Stabilization of a specific nuclear mRNA precursor by thyroid hormone.
Narayan, P., & Towle, H. C. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2642 · Cited by 46 · see citing works
Rothwell, N. J., & Stock, M. J. (1983) · Springer eBooks · doi:10.1007/978-94-011-6032-2_7 · Cited by 43 · see citing works
Sajdel-Sulkowska, E. M., Coughlin, J. F., & Marotta, C. A. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb08032.x · Cited by 35 · see citing works
Disposal Rates of Thyroxine and Triiodothyronine in Iodine-Deficient Rats
Silva, E. (1972) · Endocrinology · doi:10.1210/endo-91-6-1430 · Cited by 32 · see citing works
Brown adipose tissue: molecular mechanisms controlling activity and thermogenesis
Cannon, B., & Nedergaard, J. (1985) · Elsevier eBooks · doi:10.1016/b978-0-408-10857-7.50015-4 · Cited by 19 · see citing works
Brown Adipose Tissue Metabolism and Thermogenesis
Himms‐Hagen, J. (1985) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.5.1.69 · Cited by 16 · see citing works
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Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476 · see citing works
“These molecules are also known to upregulate UCP-1 expression in many models, including mouse [40,41], rat [42,43], and human [44] brown adipose tissues.”
BackgroundBianco, A. C., Anderson, G., Forrest, D., Galton, V. A., Gereben, B., Kim, B. W., Kopp, P. A., Liao, X. H., Obregon, M. J., Peeters, R. P., et al. (2014) · Thyroid · doi:10.1089/thy.2013.0109 · Cited by 205 · see citing works
Hypothalamic control of energy expenditure and thermogenesis
Tran, L. T., Park, S., Kim, S. K., Lee, J. S., Kim, K. W., & Kwon, O. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00741-z · Cited by 208 · see citing works
Convertible adipose tissue in mice.
Lončar, D. (1991) · Cell and Tissue Research · doi:10.1007/bf00678721 · Cited by 187 · see citing works
Golozoubova, V., Gullberg, H., Matthias, A., Cannon, B., Vennström, B., & Nedergaard, J. (2004) · Molecular Endocrinology · doi:10.1210/me.2003-0267 · Cited by 155 · see citing works
The mitochondrial uncoupling protein: structural and genetic studies.
Ricquier, D., & Bouillaud, F. (1997) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(08)61003-x · Cited by 52 · see citing works
- Authors
- Silva, J. E., & Matthews, P. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1988-08
- Volume
- 2
- Issue
- 8
- Pages
- 706-713
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2032557664
- Cited by
- 100
- References
- 31
- Citations by year
- 2024: 1 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 3 · 2014: 1 · 2013: 3
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- uncoupling proteins, norepinephrine, triiodothyronine, hypothyroidism, brown adipose tissue, cold exposure, sympathetic nervous system, adrenergic signaling, thyroid hormones, isoproterenol, thermoneutrality, denervation
- MeSH terms
- Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Carrier Proteins, Gene Expression Regulation, Genes, Ion Channels, Isoproterenol, Male, Membrane Proteins, Mitochondria, Norepinephrine, Rats, Inbred Strains, Reference Values, RNA, Messenger, Thyroid Gland, Thyroidectomy, Thyroxine, Transcription, Genetic, Triiodothyronine, Mitochondrial Proteins, Rats
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