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Published in: Diabetologia 4/2005

01-04-2005 | Commentary

The metabolic actions of thyroid hormone and leptin: a mandatory interplay or not?

Author: R. Vettor

Published in: Diabetologia | Issue 4/2005

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Excerpt

The report by P. Cettour-Rose and colleagues on the metabolic consequences of hypothyroidism in rats and their partial correction by central leptin infusion in this month’s issue of Diabetologia [1] represents a further step in highlighting the importance of both central and peripheral interplay between thyroid hormones and leptin in the control of energy metabolism. The authors measured whole-body glucose turnover by euglycaemic–hyperinsulinaemic clamp and tissue-specific glucose utilisation in propylthiouracil-induced hypothyroid rats using the labelled 2-deoxy-d-glucose technique. Leptin was infused intracerebroventricularly (i.c.v.) after the induction of hypothyroidism in a group of rats. One of the leptin-infused hypothyroid groups was additionally infused subcutaneously with reverse T3 (rT3) to inhibit type 2 deiodinase activity. Leptin-infused rats treated with rT3 were therefore deficient in both type 1 and type 2 deiodinase activities. In this paper the authors further confirm the presence of decreased overall glucose turnover and glucose utilisation in skeletal muscle and adipose tissue of hypothyroid rats, together with a reduction in leptin and an increase in resistin mRNA expression. Leptin infusion i.c.v. in hypothyroid rats partially restores the impairment in glucose metabolism, and this seems to occur independently of T3 levels and resistin expression. The effect of i.c.v. leptin also resulted in increased expression of carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content. The authors conclude that increased glucose–fatty acid competition may explain the decreased insulin responsiveness in hypothyroidism, and that this phenomenon is partly alleviated by i.c.v. leptin administration. …
Literature
1.
go back to reference Cettour-Rose P, Theander-Carrillo C, Asensio C et al (2005) Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia 48. DOI 10.1007/s00125-005-1696-4 Cettour-Rose P, Theander-Carrillo C, Asensio C et al (2005) Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia 48. DOI 10.​1007/​s00125-005-1696-4
2.
go back to reference Magnus-Levy A (1895) Ueber den respiratorischen Gaswechsel unter Einfluss de Thyroidea sowie unter verschiedenen pathologische Zustand. (Article in German). Berlin Klin Wochschr 32:650–652 Magnus-Levy A (1895) Ueber den respiratorischen Gaswechsel unter Einfluss de Thyroidea sowie unter verschiedenen pathologische Zustand. (Article in German). Berlin Klin Wochschr 32:650–652
3.
go back to reference Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81:1097–1142 Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81:1097–1142
4.
go back to reference Wang JL, Chinookoswong N, Yin S, Shi ZQ (2000) Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones. Am J Physiol Endocrinol Metab 279:E1278–E1285 Wang JL, Chinookoswong N, Yin S, Shi ZQ (2000) Calorigenic actions of leptin are additive to, but not dependent on, those of thyroid hormones. Am J Physiol Endocrinol Metab 279:E1278–E1285
5.
go back to reference Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G (1997) Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology 138:4485–4488 Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G (1997) Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology 138:4485–4488
6.
go back to reference Cusin I, Rouru J, Visser T, Burger AG, Rohner-Jeanrenaud F (2000) Involvement of thyroid hormones in the effect of intracerebroventricular leptin infusion on uncoupling protein-3 expression in rat muscle. Diabetes 49:1101–1105 Cusin I, Rouru J, Visser T, Burger AG, Rohner-Jeanrenaud F (2000) Involvement of thyroid hormones in the effect of intracerebroventricular leptin infusion on uncoupling protein-3 expression in rat muscle. Diabetes 49:1101–1105
7.
go back to reference Elmquist JK (2001) Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol Behav 74:703–708 Elmquist JK (2001) Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol Behav 74:703–708
8.
go back to reference Harris M, Aschkenasi C, Elias CF et al (2001) Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signalling. J Clin Invest 107:111–120 Harris M, Aschkenasi C, Elias CF et al (2001) Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signalling. J Clin Invest 107:111–120
9.
go back to reference Seoane LM, Carro E, Tovar S, Casanueva FF, Dieguez C (2000) Regulation of in vivo TSH secretion by leptin. Regul Pept 92:25–29CrossRef Seoane LM, Carro E, Tovar S, Casanueva FF, Dieguez C (2000) Regulation of in vivo TSH secretion by leptin. Regul Pept 92:25–29CrossRef
10.
go back to reference Kohrle J (1999) Local activation and inactivation of thyroid hormones: the deiodinase family. Mol Cell Endocrinol 151:103–119 Kohrle J (1999) Local activation and inactivation of thyroid hormones: the deiodinase family. Mol Cell Endocrinol 151:103–119
11.
go back to reference Dimitriadis GD, Leighton B, Parry-Billings M, West D, Newsholme EA (1989) Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. Biochem J 257:369–373 Dimitriadis GD, Leighton B, Parry-Billings M, West D, Newsholme EA (1989) Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. Biochem J 257:369–373
12.
go back to reference Weinstein SP, Watts J, Haber RS (1991) Thyroid hormone increases muscle fat glucose transporter gene expression in rat skeletal muscle. Endocrinology 129:455–464 Weinstein SP, Watts J, Haber RS (1991) Thyroid hormone increases muscle fat glucose transporter gene expression in rat skeletal muscle. Endocrinology 129:455–464
13.
go back to reference Casla A, Rovira A, Wells JA, Dohm GL (1990) Increased glucose transporter (GLUT4) protein expression in hyperthyroidism. Biochem Biophys Res Commun 171:182–188 Casla A, Rovira A, Wells JA, Dohm GL (1990) Increased glucose transporter (GLUT4) protein expression in hyperthyroidism. Biochem Biophys Res Commun 171:182–188
14.
go back to reference Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, Holloszy JO (2000) Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 88:2219–2226PubMed Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, Holloszy JO (2000) Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 88:2219–2226PubMed
15.
go back to reference Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE (2001) 5′-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem 276:46912–46916 Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE (2001) 5′-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem 276:46912–46916
16.
go back to reference Fisher JS, Gao J, Han DH, Holloszy JO, Nolte LA (2002) Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin. Am J Physiol Endocrinol Metab 282:E18–E23PubMed Fisher JS, Gao J, Han DH, Holloszy JO, Nolte LA (2002) Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin. Am J Physiol Endocrinol Metab 282:E18–E23PubMed
17.
go back to reference Frühbeck G, Jebb SA, Prentice AM (1998) Leptin: physiology and pathophysiology. Clin Physiol 18:399–419 Frühbeck G, Jebb SA, Prentice AM (1998) Leptin: physiology and pathophysiology. Clin Physiol 18:399–419
18.
go back to reference Kim YB, Uotani S, Pierroz DD, Flier JS, Kahn BB (2000) In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin. Endocrinology 141:2328–2339 Kim YB, Uotani S, Pierroz DD, Flier JS, Kahn BB (2000) In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin. Endocrinology 141:2328–2339
19.
go back to reference Szanto I, Kahn CR (2000) Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc Natl Acad Sci U S A 97:2355–2360 Szanto I, Kahn CR (2000) Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc Natl Acad Sci U S A 97:2355–2360
20.
go back to reference Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343CrossRefPubMed Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343CrossRefPubMed
21.
go back to reference Yu X, McCorkle S, Wang M et al (2004) Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia 47:2012–2021 Yu X, McCorkle S, Wang M et al (2004) Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia 47:2012–2021
Metadata
Title
The metabolic actions of thyroid hormone and leptin: a mandatory interplay or not?
Author
R. Vettor
Publication date
01-04-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1703-9

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