open access
Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy
, 1
Affiliations- Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
open access
Abstract
Background: Obesity is known to induce a state of lipotoxicity that affects the different organs of the body. Metformin is an antidiabetic drug commonly used in obesity treatment. It was known to improve thyroid function and its regulating hormones. Structural changes in the thyroid gland associated with obesity have not been well investigated. So, the aim of the present study is to detect structural changes in thyroid gland induced by obesity and to investigate the possible protective role of metformin therapy.
Materials and methods: Thirty adult female albino rats were divided into three groups (10 rats each). Group I (control group), group II (rats fed with a high-fat diet), and group III (rats fed with a high-fat diet and treated with metformin therapy). After 12 weeks, rats from all groups were sacrificed. Blood samples were taken for measurement of lipid profile, thyroid stimulating hormone (TSH), free T3 and free T4. Thyroid glands were extracted and processed for histological and ultrastructural study. Morphometric measurements for the colloid area of thyroid follicles and height of the follicular cells were done.
Results: Group I displayed normal biochemical parameters and architecture of the thyroid gland. Group II revealed disordered lipid profile, high TSH, free T3 and T4. Microscopically, large thyroid follicles with excessive colloid accumulation and decreased follicular cells height were seen. Some follicular cells showed pyknotic nuclei, vacuolated cytoplasm and disrupted basement membrane with mast cell infiltration of the thyroid tissue. Ultrastructurally, group II follicular cells showed loss of apical microvilli, dense shrunken nuclei, dilated endoplasmic reticulum, swollen damaged mitochondria with large intracellular vacuoles and colloid droplets. In group III, the biochemical parameters and structure of thyroid follicles were improved, and they had a near-normal appearance.
Conclusions: Obesity induced by high-fat diet in female rats structurally and functionally changed the thyroid gland in a way that may explain hypothyroidism associated with obesity. These changes were improved by metformin therapy.
Abstract
Background: Obesity is known to induce a state of lipotoxicity that affects the different organs of the body. Metformin is an antidiabetic drug commonly used in obesity treatment. It was known to improve thyroid function and its regulating hormones. Structural changes in the thyroid gland associated with obesity have not been well investigated. So, the aim of the present study is to detect structural changes in thyroid gland induced by obesity and to investigate the possible protective role of metformin therapy.
Materials and methods: Thirty adult female albino rats were divided into three groups (10 rats each). Group I (control group), group II (rats fed with a high-fat diet), and group III (rats fed with a high-fat diet and treated with metformin therapy). After 12 weeks, rats from all groups were sacrificed. Blood samples were taken for measurement of lipid profile, thyroid stimulating hormone (TSH), free T3 and free T4. Thyroid glands were extracted and processed for histological and ultrastructural study. Morphometric measurements for the colloid area of thyroid follicles and height of the follicular cells were done.
Results: Group I displayed normal biochemical parameters and architecture of the thyroid gland. Group II revealed disordered lipid profile, high TSH, free T3 and T4. Microscopically, large thyroid follicles with excessive colloid accumulation and decreased follicular cells height were seen. Some follicular cells showed pyknotic nuclei, vacuolated cytoplasm and disrupted basement membrane with mast cell infiltration of the thyroid tissue. Ultrastructurally, group II follicular cells showed loss of apical microvilli, dense shrunken nuclei, dilated endoplasmic reticulum, swollen damaged mitochondria with large intracellular vacuoles and colloid droplets. In group III, the biochemical parameters and structure of thyroid follicles were improved, and they had a near-normal appearance.
Conclusions: Obesity induced by high-fat diet in female rats structurally and functionally changed the thyroid gland in a way that may explain hypothyroidism associated with obesity. These changes were improved by metformin therapy.
Keywords
thyroid gland structure; obesity; high-fat diet; metformin
About this articleTitle
Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy
Journal
Issue
Article type
Original article
Pages
476-488
Published online
2019-09-03
Page views
2586
Article views/downloads
1356
DOI
Pubmed
Bibliographic record
Folia Morphol 2020;79(3):476-488.
Keywords
thyroid gland structure
obesity
high-fat diet
metformin
Authors
S. M. El-Sayed
H. M. Ibrahim
References (49)- Acikel Elmas M, Enes Cakıcı S, Rahmi Dur I, et al. Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell. 2019; 57: 57–65.
- Ajjan RA, Watson PF, Findlay C, et al. The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity. J Endocrinol. 1998; 158(3): 351–358.
- Alarcón-Vila C, Fabriàs G, Martínez L, et al. Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis. Oncotarget. 2015; 6(39): 41479–41496.
- Anil C, Kut A, Atesagaoglu B, et al. Metformin decreases thyroid volume and nodule size in subjects with insulin resistance: a preliminary study. Med Princ Pract. 2016; 25(3): 233–236.
- Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100(2): 342–362.
- Biondi B. Thyroid and obesity: an intriguing relationship. J Clin Endocrinol Metab. 2010; 95(8): 3614–3617.
- Buettner R, Schölmerich J, Bollheimer LC. High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring). 2007; 15(4): 798–808.
- Camastra S, Manco M, Frascerra S, et al. Daylong pituitary hormones in morbid obesity: effects of bariatric surgery. Int J Obes (Lond). 2009; 33(1): 166–172.
- Cao J, Dai DL, Yao L, et al. Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. Mol Cell Biochem. 2012; 364(1-2): 115–129.
- Chamberlain JJ, Herman WH, Leal S, et al. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association standards of medical care in diabetes. Ann Intern Med. 2017; 166(8): 572–578.
- Chow SE, Kao CH, Liu YT, et al. Resveratrol induced ER expansion and ER caspase-mediated apoptosis in human nasopharyngeal carcinoma cells. Apoptosis. 2014; 19(3): 527–541.
- Dadan J, Zbucki R RŁ, Sawicki B, et al. Activity of the thyroid parafollicular (C) cells in simple and hyperactive nodular goitre treated surgically - preliminary investigations. Folia Morphol. 2003; 62(4): 443–445.
- Divoux A, Moutel S, Poitou C, et al. Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes. J Clin Endocrinol Metab. 2012; 97(9): E1677–E1685.
- Dowling R, Goodwin PJ, Stambolic V. Understanding the benefit of metformin use in cancer treatment. BMC Med. 2011; 6(9): 33.
- Engin AB. What is lipotoxicity? Adv Exp Med Biol. 2017; 960: 197–220.
- Fournier JP, Yin H, Yu OH, et al. Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus. CMAJ. 2014; 186(15): 1138–1145.
- Gething MJ, Sambrook J. Protein folding in the cell. Nature. 1992; 355(6355): 33–45.
- Goldshmidt H, Matas D, Kabi A, et al. Persistent ER Stress Induces the Spliced Leader RNA Silencing Pathway (SLS), Leading to Programmed Cell Death in Trypanosoma brucei. PLoS Pathogens. 2010; 6(1): e1000731.
- Graziano MP, Sybertz EJ, Strader CD, et al. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest. 1997; 99(3): 385–390.
- Han H, Xin P, Zhao L, et al. Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice. Biol Trace Elem Res. 2012; 147(1-3): 233–239.
- Hong YH, Jung EY, Park Y, et al. Enzymatic improvement in the polyphenol extractability and antioxidant activity of green tea extracts. Biosci Biotechnol Biochem. 2013; 77(1): 22–29.
- Hu X, Liu Y, Wang C, et al. Metformin affects thyroid function in male rats. Oncotarget. 2017; 8(64): 107589–107595.
- Ittermann T, Markus MRP, Schipf S, et al. Metformin inhibits goitrogenous effects of type 2 diabetes. Eur J Endocrinol. 2013; 169(1): 9–15.
- Jorde U, Chokshi A, Drosatos K, et al. Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure. Circulation. 2012; 125(23): 2844–2853.
- Karawya F, Zahran N, Azzam E. Is water fluoridation a hidden cause of obesity? Histological study on thyroid follicular cells of albino rats. Egypt J Histol. 2015; 38(3): 547–557.
- Karimifar M, Aminorroaya A, Amini M, et al. ffect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial. J Res Med Sci. 2014; 19(11): 1019–1026.
- Kawasaki N, Asada R, Saito A, et al. Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep. 2012; 2: 799.
- Kronenberg H, Melmed S, Kenneth SP. Williams Textbook of Endocrinology. Acta Endocrinologica (Bucharest) Sauners, Elsevier Inc. 2007.
- Krysiak R, Okopien B. Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone. Clin Endocrinol (Oxf). 2011; 75(3): 404–406.
- Pejic RN, Lee DT. Hypertriglyceridemia. J Am Board Fam Med. 2006; 19(3): 310–316.
- Liu G, Liang L, Bray GA, et al. Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial. Int J Obes (Lond). 2017; 41(6): 878–886.
- Martín-Lacave I, Borrero MJ, Utrilla JC, et al. C cells evolve at the same rhythm as follicular cells when thyroidal status changes in rats. J Anat. 2009; 214(3): 301–309.
- Moorhead JL, Chen Y, Ma KZ, et al. Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology. 2008; 48(3): 770–781.
- Nauck M, Warnick G, Rifai N. Methods for measurement of ldl-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clin Chem. 2002; 48(2): 236–254.
- Neves JS, Oliveira SC, Pedro J, et al. Effect of metformin on TSH levels in patients with morbid obesity and diabetes mellitus. Revista Portuguesa de Diabetes. 2017; 12(4): 143–148.
- Oberley CC, Gourronc F, Hakimi S, et al. Murine epidermal side population possesses unique angiogenic properties. Exp Cell Res. 2008; 314(4): 720–728.
- Pekary AE, Hershman JM. Tumor necrosis factor, ceramide, transforming growth factor-beta1, and aging reduce Na+/I- symporter messenger ribonucleic acid levels in FRTL-5 cells. Endocrinology. 1998; 139(2): 703–712.
- Shaker SM, Magdy Y, Abd-Elaziz L, et al. Histological study on the effect of metformin on high-fat-diet-induced liver injury in adult male albino rats. Egypt J Histol. 2014; 37(3): 592–602.
- Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003; 14(3): 281–287.
- Schröder M, Kaufman RJ. ER stress and the unfolded protein response. Mutat Res. 2005; 569(1-2): 29–63.
- Shao Ss, Zhao Yf, Song Yf, et al. Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats. Acta Pharmacol Sin. 2014; 35(11): 1411–1420.
- Stienstra R, van Diepen JA, Tack CJ, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011; 108(37): 15324–15329.
- Wang H, Yang Z, Zhou B, et al. Fluoride-induced thyroid dysfunction in rats: roles of dietary protein and calcium level. Toxicol Ind Health. 2009; 25(1): 49–57.
- Weinberg JM. Lipotoxicity. Kidney Int. 2006; 70(9): 1560–1566.
- Winter WE, Signorion MR. Review: molecular thyroidology. Ann Clin Lab Sci. 2001; 31(3): 221–244.
- Xu YY, You YW, Ren XH, et al. Endoplasmic reticulum stress-mediated signaling pathway of gastric cancer apoptosis. Hepatogastroenterology. 2012; 59(120): 2377–2384.
- Yan Wj, Mu Y, Yu N, et al. Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet. J Assist Reprod Genet. 2015; 32(7): 1097–1104.
- Żelechowska P, Agier J, Kozłowska E, et al. Mast cells participate in chronic low-grade inflammation within adipose tissue. Obes Rev. 2018; 19(5): 686–697.
- Zienab AG, Ismail M, Askar E, et al. The collateral damage of sodium nitrates and alleviating properties of vitamin c on thyroid gland of adult male albino rats: toxicological, histological and ultrastructural study. Ain Shams J Forensic Med Clin Toxicol. 2013; 21(2): 98–110.
