Abstract
Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that participates in various energy metabolism pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Besides, it is a required cofactor for post-translational modifications such as ADP-ribosylation and deacetylation by poly (ADP-ribose) polymerases (PARPs) and sirtuins, respectively. Thus, NAD regulates energy metabolism, DNA damage repair, gene expression, and stress response through these enzymes. Numerous studies have shown that NAD levels decrease with aging and under disturbed nutrient conditions, such as obesity. Additionally, a decline in NAD levels is closely related to the development of various metabolic disorders, including diabetes and fatty liver disease. In addition, many studies have revealed that administration of NAD precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), efficiently increase NAD levels in various tissues and prevent such metabolic diseases. These NAD precursors are contained in natural foods, such as cow milk, vegetables, and meats. Therefore, altered NAD metabolism can be a practical target for nutritional intervention. Recently, several human clinical trials using NAD precursors have been conducted to investigate the safety, pharmacokinetics, and efficacy against metabolic disorders such as glucose intolerance. In this review, we summarize current knowledge on the implications of NAD metabolism in metabolic diseases and discuss the outcomes of recent human clinical trials.
Highlights
Metabolic syndrome is increasing worldwide and is becoming a global health concern because it is a critical risk for various life threatening diseases, including cardiovascular diseases, stroke, and cancer [1]
FANKO mice exhibit reduced food intake [68]. These results suggest that nicotinamide phophoribosyltransferase (Nampt) in adipocytes is necessary for healthy expansion during diet-induced obesity and it is important for the maintenance of insulin sensitivity in normal nutrient status
Nicotinamide adenine dinucleotide (NAD) metabolism is spotlighted as a therapeutic target for metabolic disorders, such as obesity, diabetes, dyslipidemia, and fatty liver
Summary
Metabolic syndrome is increasing worldwide and is becoming a global health concern because it is a critical risk for various life threatening diseases, including cardiovascular diseases, stroke, and cancer [1]. Deficiency of quinolinate phosphoribosyltransferase (Qprt), a key enzyme in the de novo pathway, has no effect in the NAD levels in murine tissues, including the liver [41] These results indicate that NAD synthesis in mammalian cells largely depends on the salvage pathway. Several studies have revealed that intracellular NAD levels decreased with obesity in multiple murine tissues, including the adipose tissue, skeletal muscles, liver, and hypothalamus [8, 10, 12, 15]. Islet cells in FRD-fed mice exhibited increased expression of inflammatory cytokines, including TNFα and IL-1β, whereas NMN administration reduced IL-1β expression and restored the decreased insulin secretion in FRD-fed mice, suggesting that eNampt regulates β-cell function through a mechanism of NAD synthesis [63].
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