Hypothyroidism on Lipid Metabolism

The thyroid gland is important in the human body because of its ability to produce the hormones triiodothyronine (T3) and tetraiodothyronine (T4), necessaries for appropriate energy levels and an active life. It has long been known that thyroid hormones are of vital importance in maintaining the initial level of phospholipids in cell membranes and fatty acids composition of the lipids (Prasad & Kumar, 2005). T3 plays a critical role in lipid metabolism by regulating genes involved in lipogenesis and lipolysis (Zhu & Chang, 2010). The underlying mechanisms, however, have only begun to be unraveled in recent years. Hypothyroidism, characterized by low serum thyroid hormone levels, is associated with reduced metabolism, reduced lipolysis, weight gain, reduced cholesterol clearance, and elevated serum cholesterol. It is known that thyroid hormone has genomic and nongenomic effects (Davis et al., 2008). Thyroid hormones exert their effects by stimulation of thyroid hormone receptors (TRs) that have different tissue distribution and metabolic targets. Thyroid hormone receptors possess two isoforms, TR┙ and TR┚ (Nr1a1 and Nr1a2) encoded by the TR┙ (NR1A1) and TR┚ (NR1A2) genes, and each isoform exists as two or three subtypes, respectively (┙1, ┙ 2, ┚1, ┚2, and ┚3). TR┙ plays a key role in postnatal development, adipose tissue and cardiac metabolism, whereas TR┚ regulates multiple steps in hepatic metabolism as well as thyroid hormone levels (Oetting & Yen, 2007). Nuclear mechanisms of thyroid hormone action have been extensively described but an increasing number of nongenomic effects of the hormone at the cellular level have been recognized in the past 10 years (Cheng et al. 2010). Nongenomic actions of thyroid hormone are by definition independent on nuclear receptors for the hormone and have been described at the plasma membrane, various organelles, the cytoskeleton, and in cytoplasm. The actions include alterations in the transport of solutes like Ca++, Na+ and glucose, changes in activities of several kinases, including protein kinase C, cAMP-dependent protein kinase and mitogen-activated protein kinase. Iodothyronines also can regulate nongenomically through a protein kinase C activation of neutral lipids, phospholipids and phosphatidylinositol 4, 5-bisphosphate [PtdIns (4, 5) P2] (Axelband et al., 2011).