Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels

Caterina Di Cosmo, Xiao Hui Liao, Honggang Ye, Alfonso Massimiliano Ferrara, Roy E Weiss, Samuel Refetoff, Alexandra M. Dumitrescu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Children with monocarboxylate transporter 8 (MCT8) deficiency lose weight, even when adequately nourished. Changes in serum markers of thyroid hormone (TH) action compatible with thyrotoxicosis suggested that this might be due to T3 excess in peripheral tissues. Mct8-deficient mice (Mct8KO) replicate the human thyroid phenotype and are thus suitable for metabolic studies so far unavailable in humans. In the current work, compared with wild-type (Wt) mice, Mct8KO mice were leaner due to reduced fat mass. They tended to use more carbohydrates and fewer lipids during the dark phase. Mct8KO mice had increased total energy expenditure (TEE) and food and water intake, with normal total activity, indicating hypermetabolism. To determine whether this is due to the high serum T3, we studied mice deficient in both Mct8 and deiodinase 1 (Mct8D1KO) with serum T3 similar to Wt mice and Wt mice given L-T3 to raise their serum T3 to the level of Mct8KO mice. Contrary to Mct8KO, Mct8D1KO mice had similar fat mass, TEE, and food intake as their D1KO littermates, whereas T3-treated Wt mice showed increased food intake and TEE, similar to Mct8KO mice. In skeletal muscle, Mct8KO mice had increased T3 content and TH action and increased glucose metabolism, which improved in Mct8D1KO mice. These studies indicate that the high serum T3 in MCT8 deficiency increases the TEE and fails to maintain weight despite adequate calorie intake. This is mediated by tissues that are not predominantly MCT8 dependent for TH transport, including skeletal muscle. Normalizing serum T3 level by deleting deiodinase 1 corrects body composition and the metabolic alterations caused by the MCT8 deficiency.

Original languageEnglish (US)
Pages (from-to)4885-4895
Number of pages11
JournalEndocrinology
Volume154
Issue number12
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

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Energy Metabolism
Fats
Serum
Iodide Peroxidase
Eating
Thyroid Hormones
Skeletal Muscle
Weights and Measures
Thyrotoxicosis
Triiodothyronine
Body Composition
Energy Intake
Drinking
Thyroid Gland
Biomarkers
Carbohydrates
Phenotype
Lipids
Glucose

ASJC Scopus subject areas

  • Endocrinology
  • Medicine(all)

Cite this

Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels. / Di Cosmo, Caterina; Liao, Xiao Hui; Ye, Honggang; Ferrara, Alfonso Massimiliano; Weiss, Roy E; Refetoff, Samuel; Dumitrescu, Alexandra M.

In: Endocrinology, Vol. 154, No. 12, 01.12.2013, p. 4885-4895.

Research output: Contribution to journalArticle

Di Cosmo, Caterina ; Liao, Xiao Hui ; Ye, Honggang ; Ferrara, Alfonso Massimiliano ; Weiss, Roy E ; Refetoff, Samuel ; Dumitrescu, Alexandra M. / Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels. In: Endocrinology. 2013 ; Vol. 154, No. 12. pp. 4885-4895.
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AU - Ferrara, Alfonso Massimiliano

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AU - Refetoff, Samuel

AU - Dumitrescu, Alexandra M.

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