Cardiac hypertrophy in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency

Abstract

We have reported the clinical and biochemical findings in juvenile visceral steatosis (jvs) mice with systemic carnitine deficiency. This paper is the first report about cardiomyopathy injvs mice. Adult jvs mice (at the age of 2 3 months) show cardiac hypertrophy which is caused by enlargement of the cardiac muscle cell associated with increases of non-collagen protein and DNA content. Carnitine administration (2 mg/head, twice a day, from 1 month of age) significantly suppresses the cardiac hypertrophy, showing that carnitine deficiency plays an important role in the development of the cardiac hypertrophy. The discovery of cardiac hypertrophy in carnitine-deficient jvs mice will lead to clarification of the pathophysiology of cardiomyopathy in systemic carnitine deficiency in human beings.Cardiac hypertrophy; Systemic carnitine deficiency; Animal model; Juvenile visceral steatosis mice

Carnitine is necessary to maintain the phenotype and function of brown adipose tissue

“…Role of carnitine in brown adipocytes K Ozaki et al and display a severe carnitine deficiency and the accumulation of lipid droplets in various cells (hepatocytes, renal tubular epithelial cells, cardiac myocytes, and striated myocytes). [12][13][14]17 L-carnitine administration increases the carnitine concentration and eliminates the accumulation of lipids in the liver, heart, and skeletal muscle of JVS mice. 12,14,17,26 However, tissue carnitine levels in the heart, liver, and skeletal muscle are significantly lower than those in controls, even after L-carnitine administration.…”

“…[12][13][14]17 L-carnitine administration increases the carnitine concentration and eliminates the accumulation of lipids in the liver, heart, and skeletal muscle of JVS mice. 12,14,17,26 However, tissue carnitine levels in the heart, liver, and skeletal muscle are significantly lower than those in controls, even after L-carnitine administration. 26 According to these previous reports, the effects of L-carnitine administration seem to differ among various organs.…”

“…11 The JVS phenotype is inherited in an autosomal recessive manner and is characterized by growth retardation, fatty liver, hypoglycemia, hyperammonemia, and cardiac hypertrophy. [12][13][14][15][16][17][18][19] Carnitine administration improves the characteristic symptoms of JVS mice. 15,17,18,20 Moribund JVS mice display continuous shivering, which is attributable to a decrease in heat production and an enhanced sensitivity to cold.…”

“…[12][13][14][15][16][17][18][19] Carnitine administration improves the characteristic symptoms of JVS mice. 15,17,18,20 Moribund JVS mice display continuous shivering, which is attributable to a decrease in heat production and an enhanced sensitivity to cold. 12 In a previous study, we demonstrated that the morphology of BAT in JVS mice resembles that of white adipose tissue (WAT), in which the adipocytes contain large fat droplets.…”

Functional Disorders of the Oxidative Phosphorylation System in the Heart Mitochondria of Mice with Juvenile Visceral Steatosis.

“…8,9) Horiuchi et al reported that carnitine administration corrected growth retardation and abnormal gene expression of urea-cycle enzymes and was partly effective in ameliorating the fatty liver and in suppressing the cardiac hypertrophy. 10,11) These results indicate that carnitine deficiency plays an important role in the development of these pathological features. At present, JVS mice are recognized as a novel animal model for human systemic carnitine deficiency.…”