Thyroid hormone controls carnitine status through modifications of γ-butyrobetaine hydroxylase activity and gene expression

Abstract

The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability.

Feed restriction, but not l-carnitine infusion, alters the liver transcriptome by inhibiting sterol synthesis and mitochondrial oxidative phosphorylation and increasing gluconeogenesis in mid-lactation dairy cows

“…Consistent with the stimulatory effect of thyroid hormone on lipid metabolism and CPT-1 activity (Louet et al, 2001), thyroxine administration increased hepatic BBOX1 expression, BBOX1 activity, and carnitine accumulation (Galland et al, 2002). In contrast to early postpartal cows (Schlegel et al, 2012), we observed a decrease in the expression of BBOX1 (Figure 2) with feed restriction, suggesting a decrease in endogenous synthesis of carnitine.…”

Hormonal and nutritional control of L‐carnitine uptake in myoblastic C2C12 cells

“…Thyroid hormones are known to influence fatty acid metabolism in muscle as they have been shown to increase fatty acid oxidation 9 through increases in l-carnitine biosynthesis 7 and carnitine palmitoyl transferase I (CPT I) activity. 10 The data presented herein show enhanced l-carnitine uptake in the C2C12 cells that correlated with an increase in level of OCTN2 mRNA.…”

L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial

“…In another study, there was a significantly decreased total carnitine level in skeletal muscle in hyperthyroid patients versus euthyroid individuals, and the carnitine level tended to be lower in hypothyroid patients [15]. Carnitine depletion in hyperthyroidism may be explained by increased fatty acid oxidation due to increased transcription of CPT-1, and carnitine-acylcarnitine translocase in the liver, and decreased carnitine levels in hypothyroidism may be explained by decreased biosynthesis of carnitine [10,12,13,16]. Other studies showed that carnitine inhibited the entry of thyroid hormone into the nucleus in some tissues and suggested that it is a peripheral antagonist of thyroid hormone action [17][18][19].…”

“…Because the outer mitochondrial membrane is impermeable to acyl-CoA, an acylcarnitine transportation system is essential and plays a vital role in the production of energy [7,8]. Thyroid hormone stimulates carnitine-dependent fatty acid import and oxidation [9][10][11][12] and increases carnitine bioavailability [13]. postoperative hypothyroidism after total thyroidectomy for treatment of thyroid cancer) but still experienced fatigue or fatigue-related symptoms were screened for this study.…”