Abstract
(1) Background: Diet-induced obesity inhibits hepatic carnitine biosynthesis. Herein, the effects of high-fat (HF) and high-sugar (HFHS) feeding and exercise training (ET) on renal carnitine biosynthesis and uptake were determined. (2) Methods: Male C57BL/6J mice were assigned to the following groups: lean control (standard chow), HFHS diet, and HFHS diet with ET. ET consisted of 150 min of treadmill running per week for 12 weeks. Protein levels of γ-butyrobetaine hydroxylase (γ-BBH) and organic cation transporter-2 (OCTN2) were measured as markers of biosynthesis and uptake, respectively. (3) Results: HFHS feeding induced an obese diabetic state with accompanying hypocarnitinemia, reflected by decreased free carnitine levels in plasma and kidney. This hypocarnitinemia was associated with decreased γ-BBH (~30%) and increased OCTN2 levels (~50%). ET failed to improve the obesity and hyperglycemia, but improved insulin levels and prevented the hypocarnitinemia. ET increased protein levels of γ-BBH, whereas levels of OCTN2 were decreased. Peroxisome proliferator-activated receptor-alpha content was not changed by the HFHS diet or ET. (4) Conclusions: Our results indicate that ET prevents the hypocarnitinemia induced by HFHS feeding by increasing carnitine biosynthesis in kidney. Increased expression of OCTN2 with HFHS feeding suggests that renal uptake was stimulated to prevent carnitine loss.
Highlights
Carnitine is a cofactor that exerts a fundamental role in the oxidation of long-chain fatty acids (FAs).Carnitine and the carnitine shuttle system translocate FAs from the cytosol into the mitochondria where these substrates undergo β-oxidation for the production of energy [1]
Biosynthesis originates from protein degradation of methionine and lysine, and the reactions that follow exist in most tissues, the final step in this pathway, which involves the hydroxylation of γ-butyrobetaine (BB)
We have shown that expression of γ- butyrobetaine hydroxylase (γ-BBH) and organic cation transporter-2 (OCTN2) is increased in rat and mouse tissue in response to acute and chronic exercise training (ET), with both conditions stimulating carnitine biosynthesis and increasing the levels of plasma carnitine [14,15,16]
Summary
Carnitine and the carnitine shuttle system translocate FAs from the cytosol into the mitochondria where these substrates undergo β-oxidation for the production of energy [1]. Both dietary sources of carnitine and endogenous biosynthesis are critical in regulating carnitine homeostasis. Following the release of carnitine into the plasma, the sodium-dependent organic cation transporter-2 (OCTN2). Facilitates the uptake of carnitine into peripheral tissues [4]. Expressed in kidney, this transporter has a high affinity for carnitine, and it is important in renal reabsorption of this cofactor from the urine [4]. BB released from tissues enters hepatic and renal cells by the OCTN2 transporter, Molecules 2020, 25, 2100; doi:10.3390/molecules25092100 www.mdpi.com/journal/molecules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
