Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats
Abstract
Shan-shan SHAO1, 2, Yuan-fei ZHAO3, Yong-feng SONG1, Chao XU1, Jian-mei YANG1, 2, Shi-meng XUAN2, Hui-li YAN2, Chun-xiao YU2, Meng ZHAO1, 2, Jin XU1, 2, *, Jia-jun ZHAO1, 2, *
1Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Ji-nan 250021, China; 2Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Ji-nan 250021, China; 3Shandong Provincial Hospital affiliated to Shandong University, Ji-nan 250021, China
Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats.
Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses.
Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes.
Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.
Keywords: high-fat lard diet; thyroid gland; hypertriglyceridemia; hypothyroidism; ER stress; TSH; TTF-1; NIS; lipotoxicity
This research was supported in part by grants from the National Basic Research Program (2012CB524900) and the National Natural Science Foundation of China (81230018, 81300644, and 81430020). We thank Prof Bing-bing JIANG (Boston University, USA) for the use of Image J software.
* To whom correspondence should be addressed.
E-mail jjzhao@medmail.com.cn (Jia-jun ZHAO); xujin@medmail.com.cn (Jin XU)
Received 2014-02-20 Accepted 2014-07-05
Keywords:
1Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Ji-nan 250021, China; 2Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Ji-nan 250021, China; 3Shandong Provincial Hospital affiliated to Shandong University, Ji-nan 250021, China
Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats.
Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses.
Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes.
Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.
Keywords: high-fat lard diet; thyroid gland; hypertriglyceridemia; hypothyroidism; ER stress; TSH; TTF-1; NIS; lipotoxicity
This research was supported in part by grants from the National Basic Research Program (2012CB524900) and the National Natural Science Foundation of China (81230018, 81300644, and 81430020). We thank Prof Bing-bing JIANG (Boston University, USA) for the use of Image J software.
* To whom correspondence should be addressed.
E-mail jjzhao@medmail.com.cn (Jia-jun ZHAO); xujin@medmail.com.cn (Jin XU)
Received 2014-02-20 Accepted 2014-07-05