Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice

Abstract. The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.

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“…This reduction may also be one of the factors responsible for anorexia, and also appears to be associated with reduced orexin level [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Reduced Carnitine Level Causes Death from Hypoglycemia: Possible Involvement of Suppression of Hypothalamic Orexin Expression During Weaning Period

et al. 2007

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“…Both genes are linked to lipid metabolism and are candidates for REM sleep regulation. These associations have been supported by animal studies in mice with systemic carnitine deficiency (Tafti et al, 2003), those deficient in short-chain acetyl coenzyme A dehydrogenase (Yoshida et al, 2006), and heterozygous CPT1b knockout (CPT1b ( + /-) mice (He et al, 2012).…”

Section: Discussionmentioning

confidence: 91%

“…This enzyme has been shown to be a regulator of REM sleep and wakefulness in animal models (Platt and Riedel, 2011). Thus, both genes are candidates for REM sleep regulation (Yoshida et al, 2006;Longo et al, 2006). Miyagawa et al suggested that reduced hypocretin activity may be related to decreased b-oxidation, and secondary to lower expression of CPT1B in individuals with the C allele of rs5770917, predisposing them to narcolepsy (Miyagawa et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Identification of the Variations in the CPT1B and CHKB Genes Along with the HLA-DQB1*06:02 Allele in Turkish Narcolepsy Patients and Healthy Persons

Cingoz

Agilkaya

Öztura

et al. 2014

Genetic Testing and Molecular Biomarkers

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This study identified a novel haplotype consisting of the indel variation, which had not been detected in previous studies in Japanese and Korean populations, and observed four single-nucleotide polymorphisms in CHKB/CPT1B. The study confirmed the association of the HLA-DQB1*06:02 allele with narcolepsy and cataplexy susceptibility. The findings suggest that the presence of HLA-DQB1*06:02 may be a predictor of cataplexy in narcoleptic patients and could therefore be used as an additional diagnostic marker alongside hypocretin.

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“…The glutamate released from SLD neucleus is critical for regulating REM sleep phenomena 6) . Under the mechanism of ALC, the high level of serum carnitine is able to induce the glutamate releasing in SLD 7) . As a result, it is able to enhance "REM-on" cell.…”

Section: Discussionmentioning

confidence: 99%

“…The deficiency of carnitine causes the fatty acid oxidation disturbances under fasting when fatty acids need to become a major energy source 7) . The orexin neuronal activity, which is an important role in the maintenance of wakefulness, is able to proportionally reduce with the level of serum carnitine 7) . Moreover, prolonged reduced orexin activity resultantly showed fragmentation of sleep and significant decreased amounts of REM sleep.…”

Section: Discussionmentioning

confidence: 99%

Vivid Dreaming after Acetyl-L-Carnitine Administration: A Report of Two Cases

Kim

Yoon

Park

et al. 2014

J Korean Geriatr Soc

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Acetyl-L-carnitine (ALC), an acetylated form of L-carnitine, is able to influence the activity of cholinergic neurons, cell membrane stabilization and enhancing mitochondrial function. A 52-year-old woman was referred to neurology clinic for memory impairment within 1 year. She was administered ALC as dose of 1,500 mg per day for improving memory decline. After 14 days from administrating ALC, she complained vivid dreams at every night. Vivid dream was disappeared after ceasing ALC. Another patient, a 72-year-old man, visited neurology clinic for cognitive decline for 2 years. After 20 days from administering ALC with dose of 1,500 mg per day, he also suffered from vivid dreams at every night. His previous stable sleep was also restored after ceasing ALC. ALC supplementation may present vivid dreams as a side effect. Possibility of vivid dream as a side effect should be considered during the management with oral ALC.

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Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice

Cited by 28 publications

References 44 publications

Reduced Carnitine Level Causes Death from Hypoglycemia: Possible Involvement of Suppression of Hypothalamic Orexin Expression During Weaning Period

Reduced Carnitine Level Causes Death from Hypoglycemia: Possible Involvement of Suppression of Hypothalamic Orexin Expression During Weaning Period

Identification of the Variations in the CPT1B and CHKB Genes Along with the HLA-DQB1*06:02 Allele in Turkish Narcolepsy Patients and Healthy Persons

Vivid Dreaming after Acetyl-L-Carnitine Administration: A Report of Two Cases

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