Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: Role of carnitine and lipoic acid

Sundaram, Kumaran; Panneerselvam, Kavin; Samuel, Shila; Sivarajan, Kumarasamy; Panneerselvam, C.

doi:10.1007/s11010-005-8234-z

Cited by 45 publications

(32 citation statements)

References 29 publications

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“…In these articles, the coefficients of variation [CVs; CVϭ100ϫ(sd/ mean)], calculated from data presented in data tables, appeared to be similar regardless of the treatment group or variable being measured. Subsequently, we observed a similar effect in a published article from the same investigator (1).…”

supporting

confidence: 70%

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Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India

Hudes¹,

McCann²,

Ames³

2008

FASEB j.

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A simple statistical method is described to test whether data are consistent with minimum statistical variability expected in a biological experiment. The method is applied to data presented in data tables in a subset of 84 articles among more than 200 published by 3 investigators in a small medical biochemistry department at a major university in India and to 29 "control" articles selected by key word PubMed searches. Major conclusions include: 1) unusual clustering of coefficients of variation (CVs) was observed for data from the majority of articles analyzed that were published by the 3 investigators from 2000-2007; unusual clustering was not observed for data from any of their articles examined that were published between 1992 and 1999; and 2) among a group of 29 control articles retrieved by PubMed key word, title, or title/abstract searches, unusually clustered CVs were observed in 3 articles. Two of these articles were coauthored by 1 of the 3 investigators, and 1 was from the same university but a different department. We are unable to offer a statistical or biological explanation for the unusual clustering observed.

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supporting

confidence: 70%

“…Outcome measures are as listed below. A) Kumaran et al (1): results are for skeletal muscle mitochondria isolated from young and old rats treated with l-carnitine and dl-␣-lipoic acid. Substrates were succinate, ␤-hydroxybutryate, glutamate, glutamate ϩ malate, and pyruvate ϩ malate.…”

Section: Discussionmentioning

confidence: 99%

Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India

Hudes¹,

McCann²,

Ames³

2008

FASEB j.

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“…Results from a limited number of small scale studies suggest that carnitine supplementation might confer insulin sensitizing actions in glucose intolerant or diabetic humans [16,58,72]. The precise mechanisms underlying the benefits of supplemental l -carnitine remain unclear, although mitochondrial energy metabolism and redox state have been suggested as probable targets [2,5,67,97]. Thus, by buffering intramitochondrial imbalances between acyl-CoA load and TCA cycle activity, this nutrient might play a critical role in combating the damaging effects of nutrient surplus.…”

Section: Carnitine As An Antilipotoxic Therapymentioning

confidence: 99%

Intramuscular triacylglycerol and insulin resistance: Guilty as charged or wrongly accused?

Muoio¹

2010

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

124

101

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The term lipotoxicity elicits visions of steatotic liver, fat laden skeletal muscles and engorged lipid droplets that spawn a number of potentially harmful intermediates that can wreak havoc on signal transduction and organ function. Prominent among these so-called lipotoxic mediators are signaling molecules such as long chain acyl-CoAs, ceramides and diacyglycerols; each of which is thought to engage serine kinases that disrupt the insulin signaling cascade, thereby causing insulin resistance. Defects in skeletal muscle fat oxidation have been implicated as a driving factor contributing to systemic lipid imbalance, whereas exercise-induced enhancement of oxidative potential is considered protective. The past decade of diabetes research has focused heavily on the foregoing scenario, and indeed the model is grounded in strong experimental evidence, albeit largely correlative. This review centers on mechanisms that connect lipid surplus to insulin resistance in skeletal muscle, as well as those that underlie the antilipotoxic actions of exercise. Emphasis is placed on recent studies that challenge accepted paradigms.

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“…ALCA, together with alpha-lipoic acid, was shown to improve mitochondrial energy metabolism and decrease oxidative stress leading to improved memory in aged rats [144,145]. Several studies have reported that supplementing rats with both L -carnitine and alpha-lipoic acid halts age-related increases in reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and DNA strand breaks in heart, skeletal muscle and brain, concomitant with improvement in mitochondrial enzyme and respiratory chain activities [146-149]. In a clinical trial of Levocarnitine-treated elderly patients [150], there was significant improvement in total fat mass, total muscle mass, total cholesterol, LDL-C, HDL-C, triglycerides, apoA1, and apoB with concomitant decreases in physical and mental fatigue.…”

Section: Introductionmentioning

confidence: 99%

Role of carnitine in disease

et al. 2010

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Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.

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Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: Role of carnitine and lipoic acid

Cited by 45 publications

References 29 publications

Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India

Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India

Intramuscular triacylglycerol and insulin resistance: Guilty as charged or wrongly accused?

Role of carnitine in disease

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