Characteristics of Cardiac Hypertrophy in the Juvenile Visceral Steatosis Mouse with Systemic Carnitine Deficiency

Kuwajima, Masamichi; Lu, Kang Mo; Sei, Masako; Ono, Akira; Hayashi, Miyuki; Ishiguro, Kirie; Ozaki, Kiyokazu; Hotta, Kikuko; Okita, Keisuke; Murakami, Takashi; Miyagawa, Jun Ichiro; Narama, Isao; Nikaido, Hiroko; Hayakawa, Jun-ichiro; Nakajima, Hitoshi; Namba, Mitsuyoshi; Hanafusa, Toshiaki; Matsuzawa, Yūji; Shima, Kenji

doi:10.1006/jmcc.1998.0641

Cited by 34 publications

(28 citation statements)

References 2 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…[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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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

Ozaki

Sano

Tsuji

et al. 2011

Laboratory Investigation

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The juvenile visceral steatosis (JVS) mouse is a mutant strain with an inherited systemic carnitine deficiency. Mice of this strain show clinical signs attributable to impaired heat production and disturbed energy production. Brown adipose tissue (BAT) is the primary site of non-shivering thermogenesis in the presence of uncoupling protein-1 (UCP-1) in rodents and humans, especially in infants. To investigate the possible cause of impaired heat production in BAT, we studied the morphological features, carnitine concentration, and UCP-1 production of BAT in JVS mice. The effect of carnitine administration on these parameters was also examined. JVS mice aged 5 or 10 days (60 each) and age-matched control mice were used in this study, along with 10-day-old JVS mice treated subcutaneously with L-carnitine once a day between postpartum days 5 and 10. JVS mice showed lower body temperatures and lower concentrations of carnitine in BAT. Morphologically, BAT cells in JVS mice contained large lipid vacuoles and small mitochondria, similar to those present in white adipose tissue cells. In addition, UCP-1 mRNA and protein expression levels were significantly reduced in JVS as compared with control mice. Carnitine treatment resulted in significant increases in body temperature and carnitine concentrations in BAT, together with the recovery of normal morphological features. UCP-1 mRNA and protein expression levels were also significantly increased. These findings strongly suggest that carnitine is essential for maintaining the function and morphology of BAT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

Ozaki

Sano

Tsuji

et al. 2011

Laboratory Investigation

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“…Consistent with this notion is a report indicating that administration of carnitine decreased free fatty acids in serum and tissues and prevented tissue injury in juvenile visceral steatosis (JVS) mice that lack a carnitine transporter. 47,48 It should also be noted that although carnitine lacks activity to scavenge free radicals, this amino acid shows properties similar to that of antioxidants. 26,27 The protective effects of carnitine and its acylesters might reflect their activities to improve energy metabolism and repair oxidized membrane/lipid bilayers, 49,50 thereby suppressing the release of free electrons from mitochondrial electron transport systems, a prerequisite reaction to generate free radicals.…”

Section: Discussionmentioning

confidence: 99%

L‐carnitine inhibits hepatocarcinogenesis via protection of mitochondria

Chang

Nishikawa

Nishiguchi

et al. 2004

Intl Journal of Cancer

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Hepatocellular carcinoma is usually preceded by chronic inflammation. However, the molecular mechanism in hepatocarcinogenesis is not well known. Recently, we reported that mitochondrial dysfunction plays an important role in hepatocarcinogenesis via the production of free radicals. Furthermore, we proved that L-carnitine effectively protects mitochondrial function in vivo. Therefore, we investigated whether long-term administration of L-carnitine could prevent hepatitis and subsequent hepatocellular carcinoma in Long-Evans Cinnamon rats that are often analyzed as a model of hepatocarcinogenesis. The results indicated that oxidative stress elicited from abnormally accumulated copper increased the amount of free fatty acids, thereby inducing mitochondrial dysfunction, resulting in cell death and enhanced secondary generation of reactive oxygen species, which were significantly inhibited by carnitine treatment. Finally, the occurrence of placental glutathione S-transferase-positive foci as a marker for preneoplastic lesions and hepatocarcinogenesis were significantly inhibited by L-carnitine. These facts suggest that mitochondrial injury plays an essential role in the development of hepatocarcinogenesis and that the clinical use of carnitine has excellent therapeutic potential in individuals with chronic hepatitis.

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“…[2][3][4] In JVS mice, the reabsorption system of carnitine in the kidney is defective; 5) and, as a result, carnitine levels are low in the plasma, liver, skeletal muscle, and heart. 4,6,7) Recently, it was proved that primary systemic carnitine deficiency in JVS mice is caused by a missense mutation in a gene encoding the sodium ion-dependent carnitine transporter. 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.…”

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

Suenaga

Arakaki

Morokami

et al. 2003

Biological & Pharmaceutical Bulletin

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Characteristics of Cardiac Hypertrophy in the Juvenile Visceral Steatosis Mouse with Systemic Carnitine Deficiency

Cited by 34 publications

References 2 publications

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

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

L‐carnitine inhibits hepatocarcinogenesis via protection of mitochondria

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

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