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In the present studies, cold exposure increased Dio2\u2212\/\u2212 BAT sympathetic stimulation \u223c10-fold (normal \u223c4-fold); as a result, lipolysis, as well as the mRNA levels of uncoupling protein 1, guanosine monophosphate reductase, and peroxisome proliferator\u2013activated receptor \u03b3 coactivator 1, increased well above the levels detected in the cold-exposed wild-type animals. The sustained Dio2\u2212\/\u2212 BAT adrenergic hyperresponse suppressed the three- to fourfold stimulation of BAT lipogenesis normally seen after 24\u201348 h in the cold. Pharmacological suppression of lipogenesis with \u03b2\u03b2\u2032-methyl-substituted \u03b1-\u03c9-dicarboxylic acids of C14\u2013C18 in wild-type animals also impaired adaptive thermogenesis in the BAT. These data constitute the first evidence that reduced adrenergic responsiveness does not limit cold-induced adaptive thermogenesis. Instead, the resulting compensatory hyperadrenergic stimulation prevents the otherwise normal stimulation in BAT lipogenesis during cold exposure, rapidly exhausting the availability of fatty acids. The latter is the preponderant determinant of the impaired adaptive thermogenesis and hypothermia in cold-exposed Dio2\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.2337\/diabetes.53.3.577","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"577-584","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":192,"title":["Mice with Targeted Disruption of the Dio2 Gene Have Cold-Induced Overexpression of the Uncoupling Protein 1 Gene but Fail to Increase Brown Adipose Tissue Lipogenesis and Adaptive Thermogenesis"],"prefix":"10.2337","volume":"53","author":[{"given":"Marcelo A.","family":"Christoffolete","sequence":"first","affiliation":[{"name":"Department of Medicine, Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila C.G.","family":"Linardi","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia Naomi","family":"Ebina","sequence":"additional","affiliation":[{"name":"Department of Histology & Embryology, Institute of Biomedical Sciences, University of Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy D.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam O.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Biological, Exact and Experimental Sciences, Mackenzie University, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogerio","family":"Rabelo","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyntia","family":"Curcio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciane","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Histology & Embryology, Institute of Biomedical Sciences, University of Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna T.","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Histology & Embryology, Institute of Biomedical Sciences, University of Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio C.","family":"Bianco","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031216450108600_R1","doi-asserted-by":"crossref","unstructured":"Du Bois EF: Metabolism in exophthalmic goiter. 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