Weight Loss Is Associated With Increased NAD+/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue

Tarragó

Molecular and Cellular Endocrinology

2017

163

188

Life as we know it cannot exist without the nucleotide nicotinamide adenine dinucleotide (NAD). From the simplest organism, such as bacteria, to the most complex multicellular organisms, NAD is a key cellular component. NAD is extremely abundant in most living cells and has traditionally been described to be a cofactor in electron transfer during oxidation-reduction reactions. In addition to participating in these reactions, NAD has also been shown to play a key role in cell signaling, regulating several pathways from intracellular calcium transients to the epigenetic status of chromatin. Thus, NAD is a molecule that provides an important link between signaling and metabolism, and serves as a key molecule in cellular metabolic sensoring pathways. Importantly, it has now been clearly demonstrated that cellular NAD levels decline during chronological aging. This decline appears to play a crucial role in the development of metabolic dysfunction and age-related diseases. In this review we will discuss the molecular mechanisms responsible for the decrease in NAD levels during aging. Since other reviews on this subject have been recently published, we will concentrate on presenting a critical appraisal of the current status of the literature and will highlight some controversial topics in the field. In particular, we will discuss the potential role of the NADase CD38 as a driver of age-related NAD decline.

Section: What Causes the Nad Decline Observed During The Aging Process?mentioning

confidence: 99%

NAD and the aging process: Role in life, death and everything in between

Tarragó

Molecular and Cellular Endocrinology

2017

163

188

“…For example, exercise, caloric restriction and weight-loss have been shown to increase expression of NAMPT in WAT (Fig. 2B) [69], [84], [85], [86]. In contrast, obesity, high-fat feeding and aging decrease NAMPT in WAT (Fig.…”

Section: The Maintenance Of Nad+ Homeostasis In Adipose Tissuementioning

confidence: 94%

“…Moreover, long-term calorie restriction was demonstrated to lower PARP activity in subcutaneous WAT in obese subjects (Fig. 2B) [69]. The observation that obesity is characterized with low adipose tissue NAD + levels [43], [66], [67], [68], [87] has raised an important question: what are the factors diminishing NAD + levels in adipose tissue in obesity?…”

Section: The Maintenance Of Nad+ Homeostasis In Adipose Tissuementioning

confidence: 96%

“…In spite of above mentioned pharmacological approaches, the most cost-effective therapy options to replenish the adipose tissue NAD + levels in obesity are diet-induced weight-loss and exercise, as they are known to activate NAMPT in WAT [69], [84] and attenuate PARP activation in subcutaneous WAT in obese subjects (Fig. 2B) [69].…”

Section: The Maintenance Of Nad+ Homeostasis In Adipose Tissuementioning

confidence: 99%

“…As many of the mitochondrial enzymatic pathways rely on the redox couple NAD +/ NADH, it is not surprising that obesity was recently noticed to associate with deteriorated NAD + metabolism in adipose tissue in mice [65], [66], [67] and humans [68], [69]. Thus, the preservation of adequate NAD + homeostasis is most likely essential for the function of adipose tissue mitochondrial metabolism and metabolic health.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adipose tissue NAD+-homeostasis, sirtuins and poly(ADP-ribose) polymerases -important players in mitochondrial metabolism and metabolic health

et al. 2017

Self Cite

Obesity, a chronic state of energy overload, is characterized by adipose tissue dysfunction that is considered to be the major driver for obesity associated metabolic complications. The reasons for adipose tissue dysfunction are incompletely understood, but one potential contributing factor is adipose tissue mitochondrial dysfunction. Derangements of adipose tissue mitochondrial biogenesis and pathways associate with obesity and metabolic diseases. Mitochondria are central organelles in energy metabolism through their role in energy derivation through catabolic oxidative reactions. The mitochondrial processes are dependent on the proper NAD+/NADH redox balance and NAD+ is essential for reactions catalyzed by the key regulators of mitochondrial metabolism, sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs). Notably, obesity is associated with disturbed adipose tissue NAD+ homeostasis and the balance of SIRT and PARP activities. In this review we aim to summarize existing literature on the maintenance of intracellular NAD+ pools and the function of SIRTs and PARPs in adipose tissue during normal and obese conditions, with the purpose of comprehending their potential role in mitochondrial derangements and obesity associated metabolic complications. Understanding the molecular mechanisms that are the root cause of the adipose tissue mitochondrial derangements is crucial for developing new effective strategies to reverse obesity associated metabolic complications.

Adipose tissue NAD⁺ biology in obesity and insulin resistance: From mechanism to therapy

Yamaguchi

Yoshino

2017

BioEssays

Summary Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD+ biosynthesis, together with its key downstream mediator, namely the NAD+-dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT-mediated NAD+ biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD+ biology.