N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system

Nejabati, Hamid Reza; Mihanfar, Aynaz; Pezeshkian, Masoud; Fattahi, Amir; Latifi, Zeinab; Safaie, Naser; Valiloo, Mohammad; Jodati, Ahmadreza; Nouri, Mohammad

doi:10.1002/jcp.26636

Cited by 31 publications

(15 citation statements)

References 116 publications

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“…If not recycled, nicotinamide is methylated, by the cytosolic nicotinamide N -methyltransferase (NNMT) that uses S -adenosyl-methionine (SAM) as a methyl donor, and eliminated as oxidized metabolites (Figure 3). Altered enzyme activity has been linked to several pathological conditions, including neurodegenerative diseases, obesity, type 2 diabetes and cancer [57,58,59,60,61,62,63,64]. It should be recalled that, beside nicotinamide by-products, also those deriving from conjugation of nicotinic acid to glycine (nicotinuric acid) or from its methylation (1-methylnicotinic acid) can be found in urine [65,66,67].…”

Section: Vitamin Catabolismmentioning

confidence: 99%

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

Gasperi

Sibilano

Savini

et al. 2019

IJMS

144

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Niacin (also known as “vitamin B3” or “vitamin PP”) includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death. In the central nervous system, vitamin B3 has long been recognized as a key mediator of neuronal development and survival. Here, we will overview available literature data on the neuroprotective role of niacin and its derivatives, especially focusing especially on its involvement in neurodegenerative diseases (Alzheimer’s, Parkinson’s, and Huntington’s diseases), as well as in other neuropathological conditions (ischemic and traumatic injuries, headache and psychiatric disorders).

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Section: Vitamin Catabolismmentioning

confidence: 99%

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

Gasperi

Sibilano

Savini

et al. 2019

IJMS

144

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“…MNAM is a product of methylation of nicotinamide through nicotinamide N-methyltransferase (NNMT) [6]. MNAM has been reported to decrease the concentration of blood glucose and glycosylated hemoglobin and increase C-peptide levels which are slightly elevated in diabetic rats [7].…”

Section: Introductionmentioning

confidence: 99%

N¹-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

Zhang

Chen

Liu

et al. 2020

Journal of Diabetes Research

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Objective. To explore the effects of N1-methylnicotinamide (MNAM) on insulin resistance and glucose metabolism in obese type 2 diabetes mellitus (T2DM) mice and regulatory mechanisms of the NAD-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box protein O1 (FOXO1) pathway. Methods. Blood glucose and insulin levels were examined in mice. HE and oil red O staining were used to observe the effects of MNAM on liver lipid deposition in ob/ob mice. Real-time PCR and Western blotting were used to detect expression of gluconeogenesis, insulin signaling-related proteins, and SIRT1/FOXO1 pathway-related proteins. L-O2 cells were cultured as a model of insulin resistance, and MNAM and SIRT1 inhibitors were administered in vivo. Residual glucose and insulin signaling-related proteins were detected and the mechanisms associated with the SIRT1/FOXO1 signaling pathway in insulin resistance explored. Results. MNAM can effectively reduce levels of fasting blood glucose and insulin, improve liver morphology, and reduce lipid accumulation in obese type 2 diabetes mellitus mice. MNAM also downregulates the key proteins in the gluconeogenesis pathway in the liver, upregulates Sirt1 expression, and reduces acetylation of the FOXO1 protein. In vitro, MNAM could promote the glucose uptake capacity of L-O2 cells induced by palmitic acid (PA), a saturated fatty acid that induces IR in various scenarios, including hepatocytes, improving insulin resistance. As Sirt1 expression was inhibited, the reduction of hepatocyte gluconeogenesis and the regulation of the insulin signaling pathway by MNAM were reversed. Conclusion. MNAM activates SIRT1 and inhibits acetylation of FOXO1, which in turn regulates insulin sensitivity in type 2 diabetic mice, leading to a reduction of hepatic glucose output and improvement of insulin resistance.

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“…337 Diseases that are NAD sensitive cover a variety of phenotypes and proposed mechanisms of neurotoxicity whether mitochondrial, proteotoxic, oxidative stress, or excitotoxic and whether cell body or axonal degeneration. 338–356…”

Section: A Refresh and Call To Actionmentioning

confidence: 99%

Nicotinamide and Demographic and Disease transitions: Moderation is Best

Williams

Hill

2019

Int J�Tryptophan�Res

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Good health and rapid progress depend on an optimal dose of nicotinamide. Too little meat triggers the neurodegenerative condition pellagra and tolerance of symbionts such as tuberculosis (TB), risking dysbioses and impaired resistance to acute infections. Nicotinamide deficiency is an overlooked diagnosis in poor cereal-dependant economies masquerading as ‘environmental enteropathy’ or physical and cognitive stunting. Too much meat (and supplements) may precipitate immune intolerance and autoimmune and allergic disease, with relative infertility and longevity, via the tryptophan-nicotinamide pathway. This switch favours a dearth of regulatory T (Treg) and an excess of T helper cells. High nicotinamide intake is implicated in cancer and Parkinson’s disease. Pro-fertility genes, evolved to counteract high-nicotinamide-induced infertility, may now be risk factors for degenerative disease. Moderation of the dose of nicotinamide could prevent some common diseases and personalised doses at times of stress or, depending on genetic background or age, may treat some other conditions.

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N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system

Cited by 31 publications

References 116 publications

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

N¹-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

Nicotinamide and Demographic and Disease transitions: Moderation is Best

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N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system

Cited by 31 publications

References 116 publications

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

N1-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

Nicotinamide and Demographic and Disease transitions: Moderation is Best

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N¹-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation