Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock.
Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines.
Winter
B K
BK
Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, DC 20037, USA.
Fiskum
G
G
Gallo
L L
LL
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002331:Carnitine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D015918:Infusion Pumps, Implantable; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008748:Methylcholanthrene; D009363:Neoplasm Proteins / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D014280:Triglycerides / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008748:Methylcholanthrene; D002331:Carnitine