title: Disruption of thyroid hormone activation in type 2 deiodinase knockout mice causes obesity with glucose intolerance and liver steatosis only at thermoneutrality.
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.
  
  
  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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Melany
authors.initials: M
authors.lastname: Castillo
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hall
authors.forename: Mayrin
authors.initials: M
authors.lastname: Correa-Medina
authors.forename: Cintia
authors.initials: C
authors.lastname: Ueta
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kang
authors.forename: David E
authors.initials: DE
authors.lastname: Cohen
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
mesh_terms: D000818:Animals; D001823:Body Composition / Q000235:genetics; D002153:Calorimetry, Indirect; D004041:Dietary Fats / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics; D018149:Glucose Intolerance / Q000209:etiology* / Q000235:genetics*; D005951:Glucose Tolerance Test; D007453:Iodide Peroxidase / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics*; D012333:RNA, Messenger; D013696:Temperature; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000235:genetics / Q000502:physiology; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D004041:Dietary Fats; D007453:Iodide Peroxidase; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014280:Triglycerides; D000097564:Iodothyronine Deiodinase Type II