The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38
Open accessAbstract
Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD+ metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD+ levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD+ase in mammals. Moreover, CD38 knockout mice have higher NAD+ levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD+ levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD+ levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD+ levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD+-dependent pathways.
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“For example, apigenin, a naturally occurring flavonoid, enhances NAD+ levels in human cells and mouse liver tissue, and improves glucose and lipid homeostasis in mouse models of obesity226.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [226]
In the citing paper
“For example, apigenin, a naturally occurring flavonoid, enhances NAD+ levels in human cells and mouse liver tissue, and improves glucose and lipid homeostasis in mouse models of obesity226.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [226]
In the citing paper
“have been implicated in the regulation of chromosomal integrity, DNA damage repair, metabolism, aging, health span, and longevity”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Escande et al., 2013
In the citing paper
“Sirtuins are enzymes that remove specific covalent modification in lysine residues, such as acetylation, malonylation, and succinylation, in several proteins”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Escande et al., 2013
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Global nutrition transition and the pandemic of obesity in developing countries
Popkin, B. M., Adair, L. S., & Ng, S. W. (2012) · Nutrition Reviews · doi:10.1111/j.1753-4887.2011.00456.x · Cited by 4,313
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Self-citationSmall molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796
Self-citationTranscriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
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Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750
hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S., Frye, R. A., Pandita, T. K., Guarente, L., & Weinberg, R. A. (2001) · Cell · doi:10.1016/s0092-8674(01)00527-x · Cited by 2,690
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Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
NAD+ and sirtuins in aging and disease
Imai, S.-I., & Guarente, L. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.002 · Cited by 1,481
Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.006 · Cited by 901
Self-citationTherapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.011 · Cited by 865
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Metadata
- Authors
- Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O’Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N.
- Affiliations
- Mayo Clinic (US)
- Department of Anesthesiology and Kogod Aging Center Mayo Clinic, Rochester, Minnesota
- Harvard University (US)
- Corresponding author
- Chini, Eduardo N.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-03-14
- Volume
- 62
- Issue
- 4
- Pages
- 1084-1093
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3609577
- OpenAlex
- W2112866277
- Cited by
- 332
- References
- 48
- Citations by year
- 2026: 27 · 2025: 20 · 2024: 30 · 2023: 17 · 2022: 37 · 2021: 38 · 2020: 33 · 2019: 23 · 2018: 31 · 2017: 25 · 2016: 17 · 2015: 18 · 2014: 11 · 2013: 5
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-04-01)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute on Aging (R37AG028730, T32AG000222)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK050456, R01DK084055)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- apigenin, CD38, NAD+ metabolism, sirtuins, protein acetylation, quercetin, metabolic syndrome, obesity, p53 acetylation, glucose homeostasis, lipid homeostasis, flavonoids, CD38 inhibitors
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Mice, Inbred C57BL, NAD, Obesity, Quercetin, Random Allocation, Molecular Structure, Mice, Knockout, Metabolic Syndrome, Cell Line, Tumor, Apigenin, Mice, ADP-ribosyl Cyclase 1, Sirtuin 1
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