Effect of T₃-induced hyperthyroidism on mitochondrial and cytoplasmic protein synthesis rates in oxidative and glycolytic tissues in rats

Abstract

Short KR, Nygren J, Nair KS. Effect of T3-induced hyperthyroidism on mitochondrial and cytoplasmic protein synthesis rates in oxidative and glycolytic tissues in rats. Am J Physiol Endocrinol Metab 292: E642-E647, 2007. First published October 17, 2006 doi:10.1152/ajpendo.00397.2006.-Hyperthyroidism increases metabolic rate, mitochondrial ATP production, and protein synthesis, but it remains to be determined whether all tissues and synthesis of specific protein pools are equally affected by hyperthyroidism. Previous studies showed that mitochondrial function was less responsive to elevated triiodothyronine (T3) levels in the low-oxidative plantaris muscle compared with other tissues in rats. We tested the hypothesis that in T3-treated animals mitochondrial protein synthesis would increase in oxidative but not glycolytic tissues. Male rats received either T3 (200 g/day, n ϭ 10) or saline (controls, n ϭ 9) by subcutaneous pump for 14 days, and then in vivo protein synthesis rates were measured using [15 N]phenylalanine in liver, heart, plantaris, and red gastrocnemius (Red Gast). Mitochondrial protein synthesis rate in T3-treated rats was higher than in controls by 62% in Red Gast and plantaris and 89 and 115% in liver and heart, respectively (P Ͻ 0.01). Cytoplasmic protein synthesis rates in the T3 group were 107-176% higher than control values (P Ͻ 0.01). There was also indirect evidence that protein breakdown was increased in all tissues of the T3-treated rats. Phosphorylation of selected regulators of protein synthesis in plantaris and Red Gast (mTOR, p70 S6 kinase, 4E-BP1), however, were not significantly affected by T3. We conclude that T3 infusion stimulates a general increase in mitochondrial and cytoplasmic protein synthesis rate among tissues and that this does not appear to explain the tissue-specific responses in mitochondrial oxidative capacity. protein metabolism; triiodothyronine; fractional synthesis rate; skeletal muscle HYPERTHYROIDISM INCREASES whole body metabolic rate and the metabolism of many tissues (31). The increase in metabolic rate can be attributed to increases in physical activity (17) as well as energy demand for cellular processes such as mitochondrial respiration, ion and metabolite transport, and protein turnover (22,25,26,30).

Cardiolipin Remodeling by ALCAT1 Links Oxidative Stress and Mitochondrial Dysfunction to Obesity

“…Second, ALCAT1 causes proton leakage as evidenced by up-regulation of UCP3 expression and state 4 respiration in C2C12 cells. The mitochondrial defects are similar to those observed in rodent models of diabetes, obesity, and hyperthyroidism (Boudina et al, 2007; Short et al, 2007). Third, ALCAT1 overexpression significantly increases ROS production in C2C12 cells, which is exacerbated in response to H 2 O 2 treatment.…”

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

“…Previous studies showed that thyroid hormones can regulate cardiac metabolism via multiple cellular signaling pathways [1,35]. Here we purpose also to include the sphingomyelin pathway.…”

“…Furthermore, fatty acid synthesis and oxidation in the heart are also regulated by thyroid hormones, which is initiated by binding of T 3 to nuclear its receptor. Researchers have shown that experimental hyperthyroidism results in increased mitochondrial protein synthesis most frequently in heart, liver, and oxidative skeletal muscle, but skeletal muscle with lower oxidative capacity appear to be less responsive to hyperthyroidism [8,35]. The T 3 treated rats used in the present study had significantly higher level of mitochondrial cytochrome c oxidase (COX IV) as well as β-hydroxyacyl-CoA dehydrogenase (β-HAD), and trend to increase carnityne palmitoyltransferase I (CPT1).…”

The Effect of High Glucocorticoid Administration and Food Restriction on Rodent Skeletal Muscle Mitochondrial Function and Protein Metabolism

“…The number of animals per group was chosen based on data for mitochondrial protein synthesis rate and ATP production from a prior study [20], [33]. Power to detect differences in other outcomes may be lower.…”