Metabolomic Diagnostic Technology as a Basis for the Establishing the Principles of Metabolic Health
https://doi.org/10.22416/1382-4376-2025-1894-5323
Abstract
Aim: to examine current evidence on the key metabolic alterations that reflect the major pathogenetic axes of metabolic syndrome (MS) and to assess their potential for the diagnosis and stratification of MS.
Key points. The review highlights five major metabolomic pathogenetic axes of MS: anabolic resistance, mitochondrial dysfunction, systemic inflammation, insulin resistance, and lysosomal insufficiency. Each represents an essential pathogenic link influencing the development of MS complications. Characteristic alterations of low-molecular-weight metabolites (such as amino acids and organic acids) and lipids identified through modern metabolomic analytical methods are described for each axis, and their clinical significance is discussed. Special attention is given to the role of combined metabolite panels, which improve early diagnosis of MS and prediabetes, allow risk stratification for complications (type 2 diabetes, atherosclerosis, nonalcoholic fatty liver disease, etc.), and enable monitoring of treatment effectiveness. It is noted that metabolomic biomarkers possess high diagnostic and prognostic value, complementing standard clinical indicators. Evidence is presented showing that integrating metabolomic data with clinical parameters increases diagnostic accuracy (for example, combining metabolomic markers with the glucose tolerance test improves its predictive value). The development of integrated metabolomic indices (such as MetSCORE) provides high accuracy in identifying MS (AUROC ~0.9). Metabolomic studies confirm the heterogeneity of MS and allow subclassification according to predominant pathophysiological disturbances, opening prospects for precision medicine.
Conclusion. Thus, the metabolomic approach substantially expands the possibilities for diagnosis and personalized therapy in patients with MS. It enables the detection of latent metabolic disturbances at the preclinical stage of disease, complementing routine diagnostic methods. Implementation into clinical practice requires standardization of metabolomic analytical protocols, validation of metabolomic biomarkers, and integration of multi-omics approaches, which will ensure the reproducibility of results and their broad application in medicine.
About the Authors
V. T. IvashkinRussian Federation
Vladimir T. Ivashkin — Dr. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, Head of the Department of Internal Diseases Propedeutics, Gastroenterology and Hepatology, Director of V.Kh. Vasilenko Clinic of Internal Diseases Propedeutics, Gastroenterology and Hepatology
119435, Moscow, Pogodinskaya str., 1, build. 1
O. Yu. Zolnikova
Russian Federation
Oxana Yu. Zolnikova — Dr. Sci. (Med.), Professor at the Department of Internal Disease Propaedeutics, Gastroenterology and Hepatology
119435, Moscow, Pogodinskaya str., 1, build. 1
V. V. Tarasov
Russian Federation
Vadim V. Tarasov — Dr. Sci. (Pharm.), Professor, Director of the Institute of Translational Medicine and Biotechnology, Vice-Rector for Scientific and Technological Development
119048, Moscow, Trubetskaya str, 8
S. A. Appolonova
Russian Federation
Svetlana A. Appolonova — Cand. Sci. (Chem.), Head of the Centre of Biopharmaceutical Analysis and Metabolomics at the Institute of Translational Medicine and Biotechnology
117418, Moscow, Nakhimovsky avenue, 45
References
1. Monnerie S., Comte B., Ziegler D., Morais J.A., Pujos-Guillot E., Gaudreau P. Metabolomic and lipidomic signatures of metabolic syndrome and its physiological components in adults: A systematic review. Sci Rep. 2020;10(1):669. DOI: 10.1038/s41598-019-56909-7
2. Prasun P. Mitochondrial dysfunction in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165838. DOI: 10.1016/j.bbadis.2020.165838
3. Kytikova O.Yu., Antonyuk M.V., Kantur T.A., Novgorodtseva T.P., Denisenko Yu.K. Prevalence and biomarkers in metabolic syndrome. Obesity and metabolism. 2021;18(3):302–12. (In Russ.). DOI: 10.14341/omet12704
4. Grundy S.M., Cleeman J.I., Daniels S.R., Donato K.A., Eckel R.H., Franklin B.A., et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–52. DOI: 10.1161/CIRCULATIONAHA.105.169404
5. Menikdiwela K.R., Ramalingam L., Rasha F., Wang S., Dufour J.M., Kalupahana N.S., et al. Autophagy in metabolic syndrome: Breaking the wheel by targeting the renin-angiotensin system. Cell Death Dis. 2020;11(2):87. DOI: 10.1038/s41419-020-2275-9
6. Lent-Schochet D., McLaughlin M., Ramakrishnan N., Jialal I. Exploratory metabolomics of metabolic syndrome: A status report. World J Diabetes. 2019;10(1):23–36. DOI: 10.4239/wjd.v10.i1.23
7. Ramakrishanan N., Denna T., Devaraj S., Adams-Huet B., Jialal I. Exploratory lipidomics in patients with nascent metabolic syndrome. J Diabetes Complications. 2018;32(8):791–4. DOI: 10.1016/j.jdiacomp.2018.05.014
8. Reddy P., Leong J., Jialal I. Amino acid levels in nascent metabolic syndrome: A contributor to the pro-inflammatory burden. J Diabetes Complications. 2018;32(5):465–9. DOI: 10.1016/j.jdiacomp.2018.02.005
9. Lent-Schochet D., Silva R., McLaughlin M., Huet B., Jialal I. Changes to trimethylamine-N-oxide and its precursors in nascent metabolic syndrome. Horm Mol Biol Clin Investig. 2018;35(2):/j/hmbci.2018.35.issue-2/hmbci-2018-0015/hmbci-2018-0015.xml. DOI: 10.1515/hmbci-2018-0015
10. Qiu G., Zheng Y., Wang H., Sun J., Ma H., Xiao Y., et al. Plasma metabolomics identified novel metabolites associated with risk of type 2 diabetes in two prospective cohorts of Chinese adults. Int J Epidemiol. 2016;45(5):1507–16. DOI: 10.1093/ije/dyw221
11. Nilsson M.I., Xhuti D., de Maat N.M., Hettinga B.P., Tarnopolsky M.A. Obesity and metabolic disease impair the anabolic response to protein supplementation and resistance exercise: A retrospective analysis of a randomized clinical trial with implications for aging, sarcopenic obesity, and weight management. Nutrients. 2024;16(24):4407. DOI: 10.3390/nu16244407
12. Nilsson M.I., Dobson J.P., Greene N.P., Wiggs M.P., Shimkus K.L., Wudeck E.V., et al. Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. 2013;27(10):3905–16. DOI: 10.1096/fj.12-224006
13. Whytock K.L., Goodpaster B.H. Unraveling skeletal muscle insulin resistance: Molecular mechanisms and the restorative role of exercise circulation research. Circ Res. 2025;137(2):184–204. DOI: 10.1161/CIRCRESAHA.125.325532
14. Palmer N.D., Stevens R.D., Antinozzi P.A., Anderson A., Bergman R.N., Wagenknecht L.E., et al. Metabolomic profile associated with insulin resistance and conversion to diabetes in the Insulin Resistance Atherosclerosis Study. J Clin Endocrinol Metab. 2015;100(3):E463–8. DOI: 10.1210/jc.2014-2357
15. Bustos-Arriagada E., Arazo-Rusindo M.C., Rivera-Andrades G., Pérez-Bravo F., Castillo-Valenzuela O., BarrosVelázquez J., et al. Leucine intake and sarcopenia indicators of an elderly group from the metropolitan region, Santiago de Chile, who participated in the Program for Complementary Food in Older People (PACAM). Nutrients. 2024;16(20):3540. DOI: 10.3390/nu16203540
16. Nakajima H., Okada H., Kobayashi A., Takahashi F., Okamura T., Hashimoto Y., et al. Leucine and glutamic acid as a biomarker of sarcopenic risk in Japanese people with type 2 diabetes. Nutrients. 2023;15(10):2400. DOI: 10.3390/nu15102400
17. Conde-Pipó J., Mora-Fernandez A., Martinez-Bebia M., Gimenez-Blasi N., Lopez-Moro A., Latorre J.A., et al. Intermittent fasting: Does it affect sports performance? A systematic review. Nutrients. 2024;16(1):168. DOI: 10.3390/nu16010168
18. Tornero-Aguilera J.F., Jimenez-Morcillo J., Rubio-Zarapuz A., Clemente-Suárez V.J. Central and peripheral fatigue in physical exercise explained: A narrative review. Int J Environ Res Public Health. 2022;19(7):3909. DOI: 10.3390/ijerph19073909
19. Sheffield-Moore M., Dillon E.L., Randolph K.M., Casperson S.L., White G.R., Jennings K., et al. Isotopic decay of urinary or plasma 3-methylhistidine as a potential biomarker of pathologic skeletal muscle loss. J Cachexia Sarcopenia Muscle. 2014;5(1):19–25. DOI: 10.1007/s13539-013-0117-7
20. Curcio F., Ferro G., Basile C., Liguori I., Parrella P., Pirozzi F., et al. Biomarkers in sarcopenia: A multifactorial approach. Exp Gerontol. 2016;85:1–8. DOI: 10.1016/j.exger.2016.09.007
21. Toyoshima K., Nakamura M., Adachi Y., Imaizumi A., Hakamada T., Abe Y., et al. Increased plasma proline concentrations are associated with sarcopenia in the elderly. PLoS One. 2017;12(9):e0185206. DOI: 10.1371/journal.pone.0185206
22. Bloomgarden Z. Diabetes and branched-chain amino acids: What is the link? J Diabetes. 2018;10(5):350–2. DOI: 10.1111/1753-0407.12645
23. Wang T.J., Larson M.G., Vasan R.S., Cheng S., Rhee E.P., McCabe E., et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448–53. DOI: 10.1038/nm.2307
24. Zhao X., Gang X., Liu Y., Sun C., Han Q., Wang G. Using metabolomic profiles as biomarkers for insulin resistance in childhood obesity: A systematic review. J Diabetes Res. 2016;2016:8160545. DOI: 10.1155/2016/8160545
25. Gall W.E., Beebe K., Lawton K.A., Adam K.P., Mitchell M.W., Nakhle P.J., et al.; RISC Study Group. Alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One. 2010;5(5):e10883. DOI: 10.1371/journal.pone.0010883
26. Sonkar S.K., Verma J., Sonkar G.K., Gupta A., Singh A., Vishwakarma P., et al. Assessing the role of asymmetric dimethylarginine in endothelial dysfunction: Insights into cardiovascular risk factors. Cureus. 2025;17(1):e77565. DOI: 10.7759/cureus.77565
27. Muoio D.M. Metabolic inflexibility: When mitochondrial indecision leads to metabolic gridlock. Cell. 2014;159(6):1253–62. DOI: 10.1016/j.cell.2014.11.034
28. Goodpaster B.H., Sparks L.M. Metabolic flexibility in health and disease. Cell Metab. 2017;25(5):1027–36. DOI: 10.1016/j.cmet.2017.04.015
29. Koves T.R., Ussher J.R., Noland R.C., Slentz D., Mosedale M., Ilkayeva O., et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008;7(1):45–56. DOI: 10.1016/j.cmet.2007.10.013
30. Schooneman M.G., Vaz F.M., Houten S.M., Soeters M.R. Acylcarnitines: Reflecting or inflicting insulin resistance? Diabetes. 2013;62(1):1–8. DOI: 10.2337/db12-0466
31. White H.M. The role of TCA cycle anaplerosis in ketosis and fatty liver in periparturient dairy cows. Animals (Basel). 2015;5(3):793–802. DOI: 10.3390/ani5030384
32. Berthiaume J.M., Kurdys J.G., Muntean D.M., Rosca M.G. Mitochondrial NAD+/NADH redox state and diabetic cardiomyopathy. Antioxid Redox Signal. 2019;30(3):375–98. DOI: 10.1089/ars.2017.7415
33. Li X., Yang Y., Zhang B., Lin X., Fu X., An Y., et al. Lactate metabolism in human health and disease. Signal Transduct Target Ther. 2022;7(1):305. DOI: 10.1038/s41392-022-01151-3
34. Yamakado M., Tanaka T., Nagao K., Imaizumi A., Komatsu M., Daimon T., et al. Plasma amino acid profile associated with fatty liver disease and co-occurrence of metabolic risk factors. Sci Rep. 2017;7(1):14485. DOI: 10.1038/s41598-017-14974-w
35. Nowak C., Hetty S., Salihovic S., Castillejo-Lopez C., Ganna A., Cook N.L., et al. Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance. Sci Rep. 2018;8(1):8691. DOI: 10.1038/s41598-018-26701-0
36. Jones T.E., Pories W.J., Houmard J.A., Tanner C.J., Zheng D., Zou K., et al. Plasma lactate as a marker of metabolic health: Implications of elevated lactate for impairment of aerobic metabolism in the metabolic syndrome. Surgery. 2019;166(5):861–6. DOI: 10.1016/j.surg.2019.04.017
37. Xu Z., Zhou Y., Xie R., Ning Z. Metabolomics uncovers the diabetes metabolic network: From pathophysiological mechanisms to clinical applications. Front Endocrinol (Lausanne). 2025;16:1624878. DOI: 10.3389/fendo.2025.1624878
38. Serena C., Ceperuelo-Mallafré V., Keiran N., Queipo-Ortuño M.I., Bernal R., Gomez-Huelgas R., et al. Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. ISME J. 2018;12(7):1642–57. DOI: 10.1038/s41396-018-0068-2
39. Xie J., Zhong F., Guo Z., Li X., Wang J., Gao Z., et al. Hyperinsulinemia impairs the metabolic switch to ketone body utilization in proximal renal tubular epithelial cells under energy crisis via the inhibition of the SIRT3/SMCT1 pathway. Front Endocrinol (Lausanne). 2022;13:960835. DOI: 10.3389/fendo.2022.960835
40. Fan L., Cacicedo J.M., Ido Y. Impaired nicotinamide adenine dinucleotide (NAD+) metabolism in diabetes and diabetic tissues: Implications for nicotinamide-related compound treatment. J Diabetes Investig. 2020;11(6):1403–19. DOI: 10.1111/jdi.13303
41. Semba R.D., Gonzalez-Freire M., Moaddel R., Sun K., Fabbri E., Zhang P., et al. Altered plasma amino acids and lipids associated with abnormal glucose metabolism and insulin resistance in older adults. J Clin Endocrinol Metab. 2018;103(9):3331–9. DOI: 10.1210/jc.2018-00480
42. Raza S., Rajak S, Yen P.M., Sinha R.A. Autophagy and hepatic lipid metabolism: Mechanistic insight and therapeutic potential for MASLD. NPJ Metab Health Dis. 2024;2(1):19. DOI: 10.1038/s44324-024-00022-5
43. Gunther S.H., Khoo C.M., Tai E.S., Sim X., Kovalik J.P., Ching J., et al. Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population. BMJ Open Diabetes Res Care. 2020;8(1):e001315. DOI: 10.1136/bmjdrc-2020-001315
44. Owei I., Umekwe N., Stentz F., Wan J., Dagogo-Jack S. Association of plasma acylcarnitines with insulin sensitivity, insulin secretion, and prediabetes in a biracial cohort. Exp Biol Med (Maywood). 2021;246(15):1698–705. DOI: 10.1177/15353702211009493
45. Mohammadi M., Gozashti M.H., Aghadavood M., Mehdizadeh M.R., Hayatbakhsh M.M. Clinical Significance of serum IL-6 and TNF-α levels in patients with metabolic syndrome. Rep Biochem Mol Biol. 2017;6(1):74–9.
46. Rizo-Roca D., Henderson J.D., Zierath J.R. Metabolomics in cardiometabolic diseases: Key biomarkers and therapeutic implications for insulin resistance and diabetes. J Intern Med. 2025;297(6):584–607. DOI: 10.1111/joim.20090
47. Jornayvaz F.R., Shulman G.I. Diacylglycerol activation of protein kinase Cε and hepatic insulin resistance. Cell Metab. 2012;15(5):574–84. DOI: 10.1016/j.cmet.2012.03.005
48. Xu H., Chen R., Hou X., Li N., Han Y., Ji S. The clinical potential of 1,5-anhydroglucitol as biomarker in diabetes mellitus. Front Endocrinol (Lausanne). 2024;15:1471577. DOI: 10.3389/fendo.2024.1471577
49. Guasch-Ferré M., Hruby A., Toledo E., Clish C.B., Martínez-González M.A., Salas-Salvadó J., et al. Metabolomics in prediabetes and diabetes: A systematic review and meta-analysis. Diabetes Care. 2016;39(5):833–46. DOI: 10.2337/dc15-2251
50. White P.J., McGarrah R.W., Herman M.A., Bain J.R., Shah S.H., Newgard C.B. Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street. Mol Metab. 2021;52:101261. DOI: 10.1016/j.molmet.2021.101261
51. de Mello V.D., Sehgal R., Männistö V., Klåvus A., Nilsson E., Perfilyev A., et al. Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids. Liver Int. 2021;41(4):754–63. DOI: 10.1111/liv.14743
52. Hu C., Wang T., Zhuang X., Sun Q., Wang X., Lin H., et al. Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry. J Transl Med. 2021;19(1):152. DOI: 10.1186/s12967-021-02820-7
53. Mihalik S.J., Goodpaster B.H., Kelley D.E., Chace D.H., Vockley J., Toledo F.G., et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring). 2010;18(9):1695–700. DOI: 10.1038/oby.2009.510
54. Zhao X., Han Q., Liu Y., Sun C., Gang X., Wang G. The relationship between branched-chain amino acid related metabolomic signature and insulin resistance: A systematic review. J Diabetes Res. 2016;2016:2794591. DOI: 10.1155/2016/2794591
55. Gaggini M., Carli F., Rosso C., Buzzigoli E., Marietti M., Della Latta V., et al. Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance. Hepatology. 2018;67(1):145–58. DOI: 10.1002/hep.29465
56. Shao M., Ye Z., Qin Y., Wu T. Abnormal metabolic processes involved in the pathogenesis of non-alcoholic fatty liver disease (Review). Exp Ther Med. 2020;20(5):26. DOI: 10.3892/etm.2020.9154
57. Devaraj S., Singh U., Jialal I. Human C-reactive protein and the metabolic syndrome. Curr Opin Lipidol. 2009;20(3):182–9. DOI: 10.1097/MOL.0b013e32832ac03e
58. Jayakumar S., Loomba R. Review article: Emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications. Aliment Pharmacol Ther. 2019;50(2):144–58. DOI: 10.1111/apt.15314
59. Li Z., Wang L., Ren Y., Huang Y., Liu W., Lv Z., et al. Arginase: Shedding light on the mechanisms and opportunities in cardiovascular diseases. Cell Death Discov. 2022;8(1):413. DOI: 10.1038/s41420-022-01200-4
60. Perticone F., Sciacqua A., Maio R., Perticone M., Galiano Leone G., Bruni R., et al. Endothelial dysfunction, ADMA and insulin resistance in essential hypertension. Int J Cardiol. 2010;142(3):236–41. DOI: 10.1016/j.ijcard.2008.12.131
61. Seo S.K., Kwon B. Immune regulation through tryptophan metabolism. Exp Mol Med. 2023;55(7):1371–9. DOI: 10.1038/s12276-023-01028-7
62. Tsuji A., Ikeda Y., Yoshikawa S., Taniguchi K., Sawamura H., Morikawa S., et al. The tryptophan and kynurenine pathway involved in the development of immune-related diseases. Int J Mol Sci. 2023;24(6):5742. DOI: 10.3390/ijms24065742
63. Christensen M.H.E., Fadnes D.J., Røst T.H., Pedersen E.R., Andersen J.R., Våge V., et al. Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery. PLoS One. 2018;13(2):e0192169. DOI: 10.1371/journal.pone.0192169
64. Tan K.M., Tint M.T., Kothandaraman N., Yap F., Godfrey K.M., Lee Y.S., et al. Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in prepubertal Asian children. Int J Obes (Lond). 2022;46(6):1128–37. DOI: 10.1038/s41366-022-01085-4
65. Monfort-Ferré D., Caro A., Menacho M., Martí M., Espina B., Boronat-Toscano A., et al. The gut microbiota metabolite succinate promotes adipose tissue browning in Crohn’s disease. J Crohns Colitis. 2022;16(10):1571– 83. DOI: 10.1093/ecco-jcc/jjac069
66. Rakhmat I.I., Nugraha G.I., Ariyanto E.F., Pratiwi Y.S., Linasari D., Fatimah S.N., et al. Strong association of metabolic parameters with ADMA and VCAM-1 in normo-weight subjects with metabolic syndrome. Diabetes Metab Syndr Obes. 2024;17:833–9. DOI: 10.2147/DMSO.S448650
67. Nishiyama Y., Otsuka T., Ueda M., Inagaki H., Muraga K., Abe A., et al. Asymmetric dimethylarginine is related to the predicted stroke risk in middle-aged Japanese men. J Neurol Sci. 2014;338(1–2):87–91. DOI: 10.1016/j.jns.2013.12.021
68. Tan Y., Liu X., Yang Y., Li B., Yu F., Zhao W., et al. Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia. Front Endocrinol (Lausanne). 2023;14:1119782. DOI: 10.3389/fendo.2023.1119782
69. Timmerman K.L., Volpi E. Endothelial function and the regulation of muscle protein anabolism in older adults. Nutr Metab Cardiovasc Dis. 2013;23 Suppl 1(0 1):S44–50. DOI: 10.1016/j.numecd.2012.03.013
70. Barrea L., Annunziata G., Muscogiuri G., Di Somma C., Laudisio D., Maisto M., et al. Trimethylamine-N-oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome. Nutrients. 2018;10(12):1971. DOI: 10.3390/nu10121971
71. Oktaviono Y.H., Dyah Lamara A., Saputra P.B.T., Arnindita J.N., Pasahari D., Saputra M.E., et al. The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review. Biomol Biomed. 2023;23(6):936–48. DOI: 10.17305/bb.2023.8893
72. Vanholder R., Schepers E., Pletinck A., Nagler E.V., Glorieux G. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review. J Am Soc Nephrol. 2014;25(9):1897–907. DOI: 10.1681/ASN.2013101062
73. Pallister T., Jackson M.A., Martin T.C., Zierer J., Jennings A., Mohney R.P., et al. Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome. Sci Rep. 2017;7(1):13670. DOI: 10.1038/s41598-017-13722-4
74. Saban Güler M., Arslan S., Ağagündüz D., Cerqua I., Pagano E., Berni Canani R., et al. Butyrate: A potential mediator of obesity and microbiome via different mechanisms of actions. Food Res Int. 2025;199:115420. DOI: 10.1016/j.foodres.2024.115420
75. Kasumov T., Edmison J.M., Dasarathy S., Bennett C., Lopez R., Kalhan S.C. Plasma levels of asymmetric dimethylarginine in patients with biopsy-proven nonalcoholic fatty liver disease. Metabolism. 2011;60(6):776–81. DOI: 10.1016/j.metabol.2010.07.027
76. Udovin L., Bordet S., Barbar H., Otero-Losada M., Pérez-Lloret S., Capani F. Metabolic syndrome and Parkinson’s disease: Two villains join forces. Brain Sci. 2025;15(7):706. DOI: 10.3390/brainsci15070706
77. Moon J., Kim O.Y., Jo G., Shin M.J. Alterations in circulating amino acid metabolite ratio associated with arginase activity are potential indicators of metabolic syndrome: The Korean Genome and Epidemiology Study. Nutrients. 2017;9(7):740. DOI: 10.3390/nu9070740
78. Ren Q., Sun Q., Fu J. Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease. Autophagy. 2024;20(2):221–41. DOI: 10.1080/15548627.2023.2254191
79. Zhang S., Peng X., Yang S., Li X., Huang M., Wei S., et al. The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders. Cell Death Dis. 2022;13(2):132. DOI: 10.1038/s41419-022-04593-3
80. Araujo T.F., Cordeiro A.V., Vasconcelos D.A.A., Vitzel K.F., Silva V.R.R. The role of cathepsin B in autophagy during obesity: A systematic review. Life Sci. 2018;209:274–81. DOI: 10.1016/j.lfs.2018.08.024
81. Xu Q., Mariman E.C.M., Goossens G.H., Blaak E.E., Jocken J.W.E. Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans. Adipocyte. 2020;9(1):246–52. DOI: 10.1080/21623945.2020.1775035
82. Tanaka S., Hikita H., Tatsumi T., Sakamori R., Nozaki Y., Sakane S., et al. Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice. Hepatology. 2016;64(6):1994–2014. DOI: 10.1002/hep.28820
83. Seo J.H., Koh J.M., Cho H.J., Kim H., Lee Y.S., Kim S.J., et al. Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men. J Cachexia Sarcopenia Muscle. 2024;15(6):2476–86. DOI: 10.1002/jcsm.13582
84. Field B.C., Gordillo R., Scherer P.E. The role of ceramides in diabetes and cardiovascular disease regulation of ceramides by adipokines. Front Endocrinol (Lausanne). 2020;11:569250. DOI: 10.3389/fendo.2020.569250
85. Ding L., Goossens G.H., Oligschlaeger Y., Houben T., Blaak E.E., Shiri-Sverdlov R. Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans. Diabetologia. 2020;63(2):374–84. DOI: 10.1007/s00125-019-05025-2
86. Sen P., Govaere O., Sinioja T., McGlinchey A., Geng D., Ratziu V., et al. Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease. iScience. 2022;25(9):104949. DOI: 10.1016/j.isci.2022.104949
87. Gęgotek A., Skrzydlewska E. Lipid peroxidation products’ role in autophagy regulation. Free Radic Biol Med. 2024;212:375–83. DOI: 10.1016/j.freeradbiomed.2024.01.001
88. Bhore N., Bogacki E.C., O’Callaghan B., Plun-Favreau H., Lewis P.A., Herbst S. Common genetic risk for Parkinson’s disease and dysfunction of the endolysosomal system. Philos Trans R Soc Lond B Biol Sci. 2024;379(1899):20220517. DOI: 10.1098/rstb.2022.0517
89. Ma D., Molusky M.M., Song J., Hu C.R., Fang F., Rui C., et al. Autophagy deficiency by hepatic FIP200 deletion uncouples steatosis from liver injury in NAFLD. Mol Endocrinol. 2013;27(10):1643–54. DOI: 10.1210/me.2013-1153
90. Li Q.R., Xu H.Y., Ma R.T., Ma Y.Y., Chen M.J. Targeting autophagy: A promising therapeutic strategy for diabetes mellitus and diabetic nephropathy. Diabetes Ther. 2024;15(10):2153–82. DOI: 10.1007/s13300-024-01641-3
91. Drzewoski J., Hanefeld M. The current and potential therapeutic use of metformin — the good old drug. Pharmaceuticals (Basel). 2021;14(2):122. DOI: 10.3390/ph14020122
Review
For citations:
Ivashkin V.T., Zolnikova O.Yu., Tarasov V.V., Appolonova S.A. Metabolomic Diagnostic Technology as a Basis for the Establishing the Principles of Metabolic Health. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2025;35(6):7-26. https://doi.org/10.22416/1382-4376-2025-1894-5323
JATS XML




























