Sirtuin activation as a therapeutic approach against inborn errors of metabolism

Bleeker, Jeannette C.; Houtkooper, Riekelt H.

doi:10.1007/s10545-016-9939-8

Cited by 11 publications

(6 citation statements)

References 108 publications

(140 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SIRT3, which is localized in the mitochondrial matrix, targets many proteins involved in metabolic homeostasis, including OXPHOS subunits ( 42 ). Acetylation of mitochondrial proteins propagates metabolic inflexibility and deacetylation promotes metabolic flexibility ( 178 , 259 ).…”

Section: Interventions To Improve Metabolic Flexibilitymentioning

confidence: 99%

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

et al. 2018

View full text Add to dashboard Cite

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage, and utilization, dependent on availability and requirement, is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue, and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage, and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways, which are regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors such as dietary composition and feeding frequency, exercise training, and use of pharmacological compounds, influence metabolic flexibility and will be discussed here. Last, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

show abstract

Section: Interventions To Improve Metabolic Flexibilitymentioning

confidence: 99%

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Resveratrol increases mitochondrial biogenesis through the activation of sirtuin 1 (SIRT1) and the downstream effector peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). It is likely that through this mechanism the enzyme activity can be increased if the mutated enzyme has some residual enzyme activity [ 166 ]. Bezafibrate acts as an agonist of peroxisome proliferator activator receptors (PPAR).…”

Section: Management Of Lcfaodsmentioning

confidence: 99%

Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle

Knottnerus

Bleeker

Wüst

et al. 2018

Rev Endocr Metab Disord

Self Cite

233

209

View full text Add to dashboard Cite

Mitochondrial fatty acid oxidation is an essential pathway for energy production, especially during prolonged fasting and sub-maximal exercise. Long-chain fatty acids are the most abundant fatty acids in the human diet and in body stores, and more than 15 enzymes are involved in long-chain fatty acid oxidation. Pathogenic mutations in genes encoding these enzymes result in a long-chain fatty acid oxidation disorder in which the energy homeostasis is compromised and long-chain acylcarnitines accumulate. Symptoms arise or exacerbate during catabolic situations, such as fasting, illness and (endurance) exercise. The clinical spectrum is very heterogeneous, ranging from hypoketotic hypoglycemia, liver dysfunction, rhabdomyolysis, cardiomyopathy and early demise. With the introduction of several of the long-chain fatty acid oxidation disorders (lcFAOD) in newborn screening panels, also asymptomatic individuals with a lcFAOD are identified. However, despite early diagnosis and dietary therapy, a significant number of patients still develop symptoms emphasizing the need for individualized treatment strategies. This review aims to function as a comprehensive reference for clinical and laboratory findings for clinicians who are confronted with pediatric and adult patients with a possible diagnosis of a lcFAOD.

show abstract

“…However, there are examples of increased needs under some mutational circumstances, such as those causing muscular dystrophy or optic atrophy. [250][251][252] The same may be true of DNA-repair or metabolic defects such as those causing ataxia-telangiectasia, Friedreich ataxia, defects in glutamine synthetase, and some cancers. [253][254][255][256] Other diseases such as Huntington's are known to have a disturbed 'de novo' pathway and an intervention with nicotinamide could work.…”

Section: Question 2: Is There a Strict Recommended Dose Of Nicotinamimentioning

confidence: 99%

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Hill

Williams

2017

Int J�Tryptophan�Res

View full text Add to dashboard Cite

Meat and vitamin B3 – nicotinamide – intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by ‘welcoming’ gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives) may be driven by positive ‘meat transitions’. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress.

show abstract

Sirtuin activation as a therapeutic approach against inborn errors of metabolism

Cited by 11 publications

References 108 publications

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Contact Info

Product

Resources

About

Sirtuin activation as a therapeutic approach against inborn errors of metabolism

Cited by 11 publications

References 108 publications

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease

Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle

Meat Intake and the Dose of Vitamin B3– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Contact Info

Product

Resources

About

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?