Disruption of thyroid hormone activation in type 2 deiodinase knockout mice causes obesity with glucose intolerance and liver steatosis only at thermoneutrality

Melany Castillo, Jessica A. Hall, Mayrin Correa-Medina, Cintia Ueta, Hye Won Kang, David E. Cohen, Antonio C. Bianco

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

OBJECTIVE - Thyroid hormone accelerates energy expenditure; thus, hypothyroidism is intuitively associated with obesity. However, studies failed to establish such a connection. In brown adipose tissue (BAT), thyroid hormone activation via type 2 deiodinase (D2) is necessary for adaptive thermogenesis, such that mice lacking D2 (D2KO) exhibit an impaired thermogenic response to cold. Here we investigate whether the impaired thermogenesis of D2KO mice increases their susceptibility to obesity when placed on a high-fat diet. RESEARCH DESIGN AND METHODS - To test this, D2KO mice were admitted to a comprehensive monitoring system acclimatized to room temperature (22°C) or thermoneutrality (30°C) and kept either on chow or high-fat diet for 60 days. RESULTS - At 22°C, D2KO mice preferentially oxidize fat, have a similar sensitivity to diet-induced obesity, and are supertolerant to glucose. However, when thermal stress is eliminated at thermoneutrality (30°C), an opposite phenotype is encountered, one that includes obesity, glucose intolerance, and exacerbated hepatic steatosis. We suggest that a compensatory increase in BAT sympathetic activation of the D2KO mice masks metabolic repercussions that they would otherwise exhibit. CONCLUSIONS - Thus, upon minimization of thermal stress, high-fat feeding reveals the defective capacity of D2KO mice for diet-induced thermogenesis, provoking a paradigm shift in the understanding of the role of the thyroid hormone in metabolism.

Original languageEnglish
Pages (from-to)1082-1089
Number of pages8
JournalDiabetes
Volume60
Issue number4
DOIs
StatePublished - Apr 1 2011

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Iodide Peroxidase
Glucose Intolerance
Fatty Liver
Thyroid Hormones
Knockout Mice
Obesity
Thermogenesis
Brown Adipose Tissue
High Fat Diet
Hot Temperature
Fats
Diet
Masks
Hypothyroidism
Energy Metabolism
Research Design
Phenotype
Glucose
Temperature
Liver

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Disruption of thyroid hormone activation in type 2 deiodinase knockout mice causes obesity with glucose intolerance and liver steatosis only at thermoneutrality. / Castillo, Melany; Hall, Jessica A.; Correa-Medina, Mayrin; Ueta, Cintia; Kang, Hye Won; Cohen, David E.; Bianco, Antonio C.

In: Diabetes, Vol. 60, No. 4, 01.04.2011, p. 1082-1089.

Research output: Contribution to journalArticle

Castillo, Melany ; Hall, Jessica A. ; Correa-Medina, Mayrin ; Ueta, Cintia ; Kang, Hye Won ; Cohen, David E. ; Bianco, Antonio C. / Disruption of thyroid hormone activation in type 2 deiodinase knockout mice causes obesity with glucose intolerance and liver steatosis only at thermoneutrality. In: Diabetes. 2011 ; Vol. 60, No. 4. pp. 1082-1089.
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