Abstract
We determined whether one single bout of exercise stimulates carnitine biosynthesis and carnitine uptake in liver and heart. Free carnitine (FC) in plasma was assayed using acetyltransferase and [14C]acetyl-CoA in Swiss Webster mice after 1 hour of moderate-intensity treadmill running or 4 hours and 8 hours into recovery. Liver and heart were removed under the same conditions for measurement of carnitine biosynthesis enzymes (liver butyrobetaine hydroxylase, γ-BBH; heart trimethyllysine dioxygenase, TMLD), organic cation transporter-2 (OCTN2, carnitine transporter), and liver peroxisome proliferator-activated receptor-alpha (PPARα, transcription factor for γ-BBH and OCTN2 synthesis). In exercised mice, FC levels in plasma decreased while heart and liver OCTN2 protein expressed increased, reflecting active uptake of FC. During recovery, the rise in FC to control levels was associated with increased liver γ-BBH expression. Protein expression of PPARα was stimulated in liver after exercise and during recovery. Interestingly, heart TMLD protein was also detected after exercise. Acute exercise stimulates carnitine uptake in liver and heart. The rapid return of FC levels in plasma after exercise indicates carnitine biosynthesis by liver is stimulated to establish carnitine homeostasis. Our results suggest that exercise may benefit patients with carnitine deficiency syndromes.
Highlights
Carnitine is an obligate cofactor that transfers long-chain fatty acids (FAs) into the mitochondria for the production of energy
Carnitine is derived from both dietary sources and endogenous biosynthesis [1]. e first reaction in carnitine biosynthesis involves the hydroxylation of trimethyllysine to 3-hydroxy-trimethyllysine by trimethyllysine dioxygenase (TMLD)
Liver is the main site for synthesis and contains all the enzymes to produce carnitine, whereas heart and skeletal muscle lack c-butyrobetaine hydroxylase (c-BBH). erefore, c-butyrobetaine is released from extrahepatic tissues into the plasma and accumulates in liver where it is hydroxylated to carnitine [3]. e uptake of carnitine from plasma by hepatic and extrahepatic tissues is facilitated by the sodium-dependent organic cation (OCTN2) transporter [4]
Summary
We determined whether one single bout of exercise stimulates carnitine biosynthesis and carnitine uptake in liver and heart. Free carnitine (FC) in plasma was assayed using acetyltransferase and [14C]acetyl-CoA in Swiss Webster mice after 1 hour of moderateintensity treadmill running or 4 hours and 8 hours into recovery. FC levels in plasma decreased while heart and liver OCTN2 protein expressed increased, reflecting active uptake of FC. The rise in FC to control levels was associated with increased liver c-BBH expression. Protein expression of PPARα was stimulated in liver after exercise and during recovery. Acute exercise stimulates carnitine uptake in liver and heart. E rapid return of FC levels in plasma after exercise indicates carnitine biosynthesis by liver is stimulated to establish carnitine homeostasis. Our results suggest that exercise may benefit patients with carnitine deficiency syndromes
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