Dietary Lysine and Carnitine: Relation to Growth and Fatty Livers in Rats

Abstract

Male weanling rats were fed a 72% rice diet containing no detectable carnitine and limiting in threonine and lysine. Such dietary conditions may simulate protein malnutrition in man. Under these conditions growth impairment, anemia, hypoproteinemia, and fatty liver developed. The study focused principally on the fatty liver syndrome which was corrected to varying extents depending on degrees of supplementation with carnitine, lysine, threonine, and appropriate combinations of these nutrients. Such reduction in fatty liver accumulation was accounted for principally by the lowering of triglycerides, but also in part of total cholesterol levels. All the data, which also included monitoring carnitine uptake by the tissues and measurement of plasma triglycerides, were consistent with the view that fatty liver accumulation occurs in amino acid deficient diets because (a) of an impairment in the synthesis of the lipoprotein complex mandatory for triglyceride secretion from the liver and (b) from a deficiency of carnitine needed for the intramitochondrial transport of fatty acids prerequisite for their oxidation.

Deficiency of Carnitine in Cachectic Cirrhotic Patients

“…In the cirrhotics, serum concentration declined from the 6th-day value of 28/18 (total/free) to 20/10 ,uM on day 12; the reduction however was not significant (P > 0.05). Urine total carnitine remained in the range [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] ,umol/day during days [6][7][8][9][10][11][12] Table II1. body weight 105-140% of ideal, and history negative for recent anorexia or weight loss) wlho died after an acute illness of a 1-3-day duration. In the cirrhotic patients' pectoral muscle, heart, liver, kidney, and brain, concentrations of both total and free carnitine wTere only 16-40% as great as in the nonhepatic, normiially nourished cases (P < 0.05).…”

“…(a) Because of anorexia, their average spontaneouis daily intake of ex nogenos carnitine was only 29 ,smol (days 1-6 of plhase B, Table LII), (b) Anorexia also cauised inadequate intake of dietary protein, including the carnitine precuirsors lysine and methionine (days 1-6, Table III). In the normal rat, these conditions, a carnitine-free diet deficient in either lysine or methionine, vill rapidly cause depletion of carnitine in muscle, liver, kidney, and brain (10)(11)(12). (c) Btut in cirrhotic man a third factor operates as well: endogenous biosynthesis of carnitine from lysine and methionine is defective.…”

Carnitine depletion as a probable cause of hyperlipidemia in uremic patients on maintenance hemodialysis.

“…In addition, the intake of protein and other nutrients are reduced in hemodialysis patients mainly because of prevention of harmful effect of nitrogen compounds. This undernutritional state of the patients is suggestive of reduced synthesis of carnitine and subsequent depletion of carnitine, because carnitine synthesis has to be ensued through adequate supply of the precursor amino acids, lysine and methionine (Tanphaichitr et al 1976; Bamji 1977, 1979). In fact, carnitine depletion could not be found in hemodialysis patients who had been supplemented with amino acids solution.…”

“…Carnitine deficiency induces triglyceride (TG) accumulation in blood and tissues (Maebashi et al 1976(Maebashi et al , 1977a(Maebashi et al , b, 1978Tanphaichitr et al 1976;Kahn and Bamji 1979), since carnitine deficiency has been characterized by the inability to oxidize free fatty acids (FFA) and by the increased synthesis of TG. Carnitine deficiency has been also observed in man and rat in undernutritional states (Tanphaichitr et al 1976(Tanphaichitr et al , 1980Mikhail and Mansour 1976;Borum and Broquist 1977;Bamji 1977, 1979;KahnSiddigui and Bamji 1980). Undernutrition in uremic patients on maintenance hemodialysis is mainly due to poor intake of protein and to loss of amino acids during hemodialysis treatment.…”

“…Undernutrition in uremic patients on maintenance hemodialysis is mainly due to poor intake of protein and to loss of amino acids during hemodialysis treatment. These changes in the nutritional status may also lead to carnitine depletion, because carnitine is synthesized from lysine and methionine (Tanphaichitr and Broquist 1973) and diminished supply for the precursor amino acids disposes to reduced synthesis of carnitine (Tanphaichitr et al 1976;Borum and Broquist 1977;Kahn and Bamji 1979). Adequate management of nutrition, such as amino acids supplementation, would improve carnitine metabolism.…”