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Exercise increases the release of NAMPT in extracellular vesicles and alters NAD⁺ activity in recipient cells.

ABSTRACT: Aging is associated with a loss of metabolic homeostasis, with cofactors such as nicotinamide adenine dinucleotide (NAD⁺ ) declining over time. The decrease in NAD⁺ production has been linked to the age-related loss of circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT), the rate-limiting enzyme in the NAD⁺ biosynthetic pathway. eNAMPT is found almost exclusively in extracellular vesicles (EVs), providing a mechanism for the distribution of the enzyme in different tissues. Currently, the physiological cause for the release of eNAMPT is unknown, and how it may be affected by age and physical exercise. Here, we show that release of small EVs into the bloodstream is stimulated following moderate intensity exercise in humans. Exercise also increased the eNAMPT content in EVs, most prominently in young individuals with higher aerobic fitness. Both mature fit and young unfit individuals exhibited a limited increase in EV-eNAMPT release following exercise, indicating that this mechanism is related to both the age and physical fitness of a person. Notably, unfit mature individuals were unable to increase the release of eNAMPT in EVs after exercise, suggesting that lower fitness levels and aging attenuate this important signalling mechanism in the body. EVs isolated from exercising humans containing eNAMPT were able to alter the abundance of NAD⁺ and SIRT1 activity in recipient cells compared to pre-exercise EVs, indicating a pathway for inter-tissue signalling promoted through exercise. Our results suggest a mechanism to limit age-related NAD⁺ decline, through the systemic delivery of eNAMPT via EVs released during exercise.

SUBMITTER: Chong MC

PROVIDER: S-EPMC9282849 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+) biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) supports adipose plasticity and the pathological progression to obesity.MethodsWe utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet.ResultsFat-specific Nampt knockout (FANKO) mice were completely resistant to high fat diet (HFD)-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted.ConclusionsThese findings indicate that adipose NAMPT plays an essential role in handling dietary lipid to modulate fat tissue plasticity, food intake, and systemic glucose homeostasis.

Project description:As the proportion of the elderly population grows rapidly, the senescence-delaying effects of Traditional Chinese Medicine is being investigated. The aim of the present study was to investigate the senescence-delaying effects of saffron in naturally aging mice. The active ingredients in an aqueous saffron extract were determined using high-performance liquid chromatography (HPLC). Mice were divided into saffron (8- and 16-months-old) and control groups (3-, 8-, and 16-months-old), and saffron extract was administered to the former groups for 8 weeks. The open field test and Barnes maze test were used to evaluate the locomotor activity, learning and memory function of the mice. The levels of inflammatory factors in the brain were determined by ELISA. In addition, the activities of acetylcholinesterase (AChE) and superoxide dismutase, and the contents of malondialdehyde and nicotinamide adenine dinucleotide (NAD+) were detected by enzyme immunoassay, and the content of NAMPT was detected by ELISA, western blotting and reverse transcription-quantitative PCR. The cellular distribution of NAMPT and synaptic density were evaluated by immunofluorescence, and the pathological morphologies of the liver, skin, kidneys were observed by hematoxylin and eosin staining. HPLC revealed that the crocin and picrocrocin contents of the saffron extract were 19.56±0.14 and 12.00±0.13%, respectively. Saffron exhibited the potential to improve the learning and memory function in aging mice as it increased synaptic density and decreased AChE activity. Also, saffron ameliorated the pathological changes associated with organ aging, manifested by increasing the number of hepatocytes and the thickness of the skin, and preventing the aging-induced ballooning and bleeding in the kidneys. Furthermore, saffron increased the contents of NAMPT and NAD+ in the brain and decreased the content of NAMPT in the serum. In addition, it changed the cellular distribution of NAMPT in aging mice, manifested as reduced NAMPT expression in microglia and astrocytes, and increased NAMPT expression in neurons. Saffron also decreased the contents of proinflammatory cytokines and oxidative stress factors in aging mice. Altogether, these findings indicate that saffron exerts senescence-delaying effects in naturally aging mice, which may be associated with the NAMPT-NAD+ pathway.

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Exercise increases the release of NAMPT in extracellular vesicles and alters NAD⁺ activity in recipient cells.

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Dataset Information

Exercise increases the release of NAMPT in extracellular vesicles and alters NAD+ activity in recipient cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Exercise increases the release of NAMPT in extracellular vesicles and alters NAD⁺ activity in recipient cells.