Metabolic analysis as a driver for discovery, diagnosis, and therapy

DeBerardinis, Ralph J.; Keshari, Kayvan R.

doi:10.1016/j.cell.2022.06.029

Cited by 80 publications

(38 citation statements)

References 89 publications

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“…Metabolism is the general term for a series of ordered chemical reactions that take place in the body to sustain life. 104,105 These processes allow organisms to grow and reproduce, maintain their structure and respond to the external environment. [106][107][108] Metabolism mainly includes glucose metabolism and lipid metabolism.…”

Section: The Regulatory Role Of Sirts In Cellular Biologymentioning

confidence: 99%

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The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

296

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Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

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Section: The Regulatory Role Of Sirts In Cellular Biologymentioning

confidence: 99%

“…[106][107][108] Metabolism mainly includes glucose metabolism and lipid metabolism. 104,109 Many metabolic processes occur in the mitochondria where SIRT3-5 proteins are located. In addition, SIRT proteins located in the nucleus may participate in regulating several metabolism-related genes.…”

Section: The Regulatory Role Of Sirts In Cellular Biologymentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

296

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“…Thus, by inhibiting the metabolic pathways of tumor cells, the occurrence and development of tumors could be prevented. Therefore, targeting tumor metabolism is a promising therapeutic approach ( Wang et al, 2022b ; DeBerardinis and Keshari, 2022 ; Reyes-Castellanos and Carrier, 2022 ). Metabonomic results indicated that STA treatment decreased the production of D-glucose, lactate, L-alanine, L-proline, and serine.…”

Section: Discussionmentioning

confidence: 99%

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Feng

Pan

et al. 2022

Front. Pharmacol.

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Schisantherin A (STA) is a traditional Chinese medicine extracted from the plant Schisandra chinensis, which has a wide range of anti-inflammatory, antioxidant, and other pharmacological effects. This study investigates the anti-hepatocellular carcinoma effects of STA and the underlying mechanisms. STA significantly inhibits the proliferation and migration of Hep3B and HCCLM3 cells in vitro in a concentration-dependent manner. RNA-sequencing showed that 77 genes are upregulated and 136 genes are downregulated in STA-treated cells compared with untreated cells. KEGG pathway analysis showed significant enrichment in galactose metabolism as well as in fructose and mannose metabolism. Further gas chromatography-mass spectrometric analysis (GC-MS) confirmed this, indicating that STA significantly inhibits the glucose metabolism pathway of Hep3B cells. Tumor xenograft in nude mice showed that STA has a significant inhibitory effect on tumor growth in vivo. In conclusion, our results indicate that STA can inhibit cell proliferation by regulating glucose metabolism, with subsequent anti-tumor effects, and has the potential to be a candidate drug for the treatment of liver cancer.

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“…Accordingly, intracellular metabolite concentrations are key quantities that affect the rates of metabolic reactions (fluxes) and regulate various layers of cellular organization 2,3 . Consequently, metabolite dysregulation underlies various human diseases, from metabolic disorders to cancer 4 . Given the tight associations between metabolite concentrations and cellular physiology, it is often supposed that evolutionary changes in the metabolome contribute to phenotypic differences between species 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Principles of metabolome conservation in animals

Liska

Boross

Rocabert³

et al. 2022

Preprint

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Metabolite concentrations shape cellular physiology and disease susceptibility, yet the general principles governing metabolome evolution are largely unknown. Here we introduce a measure of conservation of individual metabolite concentrations among related species. By analysing multispecies metabolome datasets in mammals and fruit flies, we show that conservation varies extensively across metabolites. Three major functional properties, metabolite abundance, essentiality and association with human diseases predict conservation, highlighting a striking parallel between the evolutionary forces driving metabolome and protein sequence conservation. Metabolic network simulations recapitulated these general patterns, and revealed that abundant metabolites are highly conserved due to their strong coupling to key metabolic fluxes in the network. This study uncovers simple rules governing metabolic evolution in animals and implies that most metabolome differences between species are permitted, rather than favored by selection. More broadly, our work paves the way towards using evolutionary information to discover biomarkers, as well as to detect pathogenic metabolome alterations in individual patients.

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Metabolic analysis as a driver for discovery, diagnosis, and therapy

Cited by 80 publications

References 89 publications

The sirtuin family in health and disease

The sirtuin family in health and disease

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Principles of metabolome conservation in animals

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