Effect of high-fat diet-induced obesity on thyroid gland structure in female rats and the possible ameliorating effect of metformin therapy.

Abstract

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. 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. 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. 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.