title: Thyroid dysfunction associated with follicular cell steatosis in obese male mice and humans.
abstract: Adult thyroid dysfunction is a common endocrine disorder associated with an increased risk of cardiovascular disease and mortality. A recent epidemiologic study revealed a link between obesity and increased prevalence of hypothyroidism. It is conceivable that excessive adiposity in obesity might lead to expansion of the interfollicular adipose (IFA) depot or steatosis in thyroid follicular cells (thyroid steatosis, TS). In this study, we investigated the morphological and functional changes in thyroid glands of obese humans and animal models, diet-induced obese (DIO), ob/ob, and db/db mice. Expanded IFA depot and TS were observed in obese patients. Furthermore, DIO mice showed increased expression of lipogenesis-regulation genes, such as sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor γ (PPARγ), acetyl coenzyme A carboxylase (ACC), and fatty acid synthetase (FASN) in the thyroid gland. Steatosis and ultrastructural changes, including distension of the endoplasmic reticulum (ER) and mitochondrial distortion in thyroid follicular cells, were uniformly observed in DIO mice and genetically obese mouse models, ob/ob and db/db mice. Obese mice displayed a variable degree of primary thyroid hypofunction, which was not corrected by PPARγ agonist administration. We propose that systemically increased adiposity is associated with characteristic IFA depots and TS and may cause or influence the development of primary thyroid failure.
authors.affiliation: Research Center for Endocrine and Metabolic Diseases (M.H.L., K.H.J., Y.K.K., M.J.R., S.E.L., S.J.K., H.K.C., M.J.C., J.Y.C., H.J.K., K.S.K., Y.S.J., M.C.), Chungnam National University School of Medicine, Daejeon 301-721, Republic of Korea; Department of Pathology (J.U.L.), Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon 301-723, Republic of Korea; Department of Biomedical Science (S.-H.L.), Korea Advanced Institute of Biological Science, Daejeon 305-701, Korea; Department of Biochemistry (G.R.K.), Chungnam National University School of Medicine, Daejeon 301-721, Republic of Korea; Department of Nuclear Medicine (S.-M.K.), Chungnam National University and Hospital, Daejeon 301-721, Republic of Korea; and Laboratory of Molecular Biology (J.P., S.-Y.C.), National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Jung Uee
authors.initials: JU
authors.lastname: Lee
authors.forename: Kyong Hye
authors.initials: KH
authors.lastname: Joung
authors.forename: Yong Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Seong Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Soung Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyo Kyun
authors.initials: HK
authors.lastname: Chung
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Choi
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Chang
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Koon Soon
authors.initials: KS
authors.lastname: Kim
authors.forename: Seong-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jo
authors.forename: Jeongwon
authors.initials: J
authors.lastname: Park
authors.forename: Sheue-Yann
authors.initials: SY
authors.lastname: Cheng
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism / Q000473:pathology*; D008055:Lipids; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology* / Q000473:pathology*
chemical_list: D004041:Dietary Fats; D008055:Lipids