Thyroid Dysfunction Associated With Follicular Cell Steatosis in Obese Male Mice and Humans

• DOI: 10.1210/en.2014-1670
• Publication Date: 2015-01-02T17:57:50Z
• Authors: Min Hee Lee; Jung Uee Lee; Kyong Hye Joung; Yong Kyung Kim; Min Jeong Ryu; Seong Eun Lee; Soung Jung Kim; Hyo Kyun Chung; Min Jeong Choi; Joon Young Chang; Sang-Hee Lee; Gi Ryang Kweon; Hyun Jin Kim; Koon Soon Kim; Seong-Min Kim; Young Suk Jo; Jeongwon Park; Sheue-Yann Cheng; Minho Shong
• Keywords: Male; 570; Thyroid Gland/pathology*; Thyroid Gland; 610; Mice, Obese; Inbred C57BL; Obese; Mice; 03 medical and health sciences; Hypothyroidism; Mice, Inbred NOD; Animals; Humans; Obesity; Adipose Tissue/pathology*; Hypothyroidism/pathology*; 2. Zero hunger; 0303 health sciences; Obesity/metabolism*; Dietary Fats; Lipids; 3. Good health; Mice, Inbred C57BL; Hypothyroidism/metabolism; Thyroid Gland/cytology*; Adipose Tissue; Dietary Fats/adverse effects; Inbred NOD

AbstractAdult 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.