Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats

Abstract

The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.

Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

“…However, CPT-1 inhibition has been linked to reduced FAO, but upregulated glucose oxidation and improved whole-body glucose tolerance and insulin sensitivity in a mouse model [ 18 , 23 ]. Further supporting the potential clinical relevance of our findings, studies of carnitine supplementation have reported improved FAO, reduced oxidative stress, as well as improved lipid metabolism [ 24 – 26 ]. Overall, our study contributes to the growing body of evidence in support of pursing therapeutics centered on the CPT enzymes and/or their biochemical pathways.…”

Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxorubicin‐treated rats

“…As carnitine acts as a transporter of long‐chain fatty acid from cytoplasmic compartment into mitochondria, where enzymatic beta‐oxidation and energy production occur, it may have participated in the reduction in any derangement of the testicular lipid metabolism that occurred in doxorubicin‐treated rats, contributing to the reduction of the damage in germ cells. Reinforcing this idea, in non‐obese hereditary hypertriglyceridemic rats carnitine improves the lipid metabolism and has potential protective action against oxidative stress produced in some metabolic syndrome‐related disorders (Cahova et al ., ).…”

Deterioration of mitochondrial bioenergetics and ultrastructure impairment in skeletal muscle of a transgenic minipig model in the early stages of Huntington's disease

“…The pyruvate dehydrogenase activity was determined by measuring the 14 CO 2 produced by the decarboxylation of [1-14C]pyruvate in an assay containing 20-50 µg mitochondrial protein, as previously described (Cahova et al, 2015).…”