{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:56:34Z","timestamp":1785412594209,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Local Special Project for Great Health","award":["2022BCE033"],"award-info":[{"award-number":["2022BCE033"]}]},{"DOI":"10.13039\/501100014361","name":"Hubei University of Medicine","doi-asserted-by":"publisher","award":["YC202532"],"award-info":[{"award-number":["YC202532"]}],"id":[{"id":"10.13039\/501100014361","id-type":"DOI","asserted-by":"publisher"}]},{"award":["YC202532"],"award-info":[{"award-number":["YC202532"]}],"id":[{"id":"https:\/\/ror.org\/01dr2b756","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL\/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg\/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic \u03b2-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p &lt; 0.05) and CRP levels (p &lt; 0.01), and alleviated dyslipidemia (p &lt; 0.05 or p &lt; 0.01), as well as \u03b2-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism.<\/jats:p>","DOI":"10.3390\/metabo16050335","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:36:40Z","timestamp":1779107800000},"page":"335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Angiotensin (1-7) on Serum Metabolomics in Obese Type 2 Diabetic Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Qiyuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Suizhou Hospital, Hubei University of Medicine, Suizhou 441300, China"},{"name":"Center for Translational Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou 441300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Suizhou Hospital, Hubei University of Medicine, Suizhou 441300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou 441300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Suizhou Hospital, Hubei University of Medicine, Suizhou 441300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Galicia, G.U., and Benito, V.A. (2020). Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176275"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ahluwalia, T.S., and Kilpel\u00e4inen, T.O. (2019). Novel biomarkers for type 2 diabetes. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00649"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170627","DOI":"10.1016\/j.peptides.2021.170627","article-title":"Alamandine, a derivative of angiotensin-(1-7), alleviates sepsis-associated renal inflammation and apoptosis by inhibiting the PI3K\/Akt and MAPK pathways","volume":"146","author":"Hu","year":"2021","journal-title":"Peptides"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1007\/s00467-020-04759-1","article-title":"2020 update on the renin-angiotensin-aldosterone system in pediatric kidney disease and its interactions with coronavirus","volume":"36","author":"Silva","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_5","first-page":"459","article-title":"A crucial role of angiotensin-converting enzyme 2 (ACE2) in SARS-CoV-2 infection","volume":"581","author":"Kuba","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"391476","DOI":"10.1155\/2014\/391476","article-title":"Ang-(1-7) protects islet endothelial cells from palmitate-induced apoptosis by AKT, eNOS, p38 MAPK and JNK pathways","volume":"2014","author":"Yuan","year":"2014","journal-title":"J. Diabetes Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.3892\/ijmm.2014.1917","article-title":"The angiotensin-converting enzyme 2\/angiotensin-(1-7)\/Mas axis protects the function of pancreatic \u03b2 cells by improving the function of islet microvascular endothelial cells","volume":"34","author":"Lu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_8","first-page":"931","article-title":"Ang-(1-7) treatment attenuates \u03b2-cell dysfunction by improving pancreatic microcirculation in a rat model of type 2 diabetes","volume":"36","author":"Yuan","year":"2013","journal-title":"J. Endocrinol. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jare.2025.01.033","article-title":"Integrated multi-omics reveals the Bacillus amyloliquefaciens BA40 against Clostridium perfringens infection in weaned piglets","volume":"77","author":"Jiang","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/s41467-025-56988-3","article-title":"Rhizobacteria protective hydrogel to promote plant growth and adaption to acidic soil","volume":"16","author":"Feng","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jare.2025.01.003","article-title":"Ginseng-derived GABAFG ameliorates type 2 diabetes mellitus by modulating autophagy-lysosome pathway and gut microbiota","volume":"77","author":"Qi","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4093\/dmj.2021.0280","article-title":"Insulin resistance: From mechanisms to therapeutic strategies","volume":"46","author":"Lee","year":"2022","journal-title":"Diabetes Metab. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"648","DOI":"10.2337\/dc12-0895","article-title":"Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults","volume":"36","author":"Soininen","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1345","DOI":"10.1210\/clinem\/dgad708","article-title":"Sex differences in branched-chain amino acid and tryptophan metabolism and pathogenesis of youth-onset type 2 diabetes","volume":"109","author":"Hernandez","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tanase, D.M., and Gosav, E.M. (2022). Oxidative stress and NRF2\/KEAP1\/ARE pathway in diabetic kidney disease (DKD): New perspectives. Biomolecules, 12.","DOI":"10.3390\/biom12091227"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40203-020-00058-7","article-title":"Are losartan and imatinib effective against SARS-CoV-2 pathogenesis? A pathophysiologic-based in silico study","volume":"9","author":"Nejat","year":"2020","journal-title":"In Silico Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13856","DOI":"10.1111\/obr.13856","article-title":"Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases","volume":"26","author":"Mansoori","year":"2025","journal-title":"Obes. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e72593","DOI":"10.7554\/eLife.72593","article-title":"Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism","volume":"10","author":"Ryan","year":"2021","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00210-022-02252-0","article-title":"GDH promotes isoprenaline-induced cardiac hypertrophy by activating mTOR signaling via elevation of alpha-ketoglutarate level","volume":"395","author":"Lin","year":"2022","journal-title":"Naunyn-Schmiedeberg\u2032s Arch. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nchembio.1961","article-title":"Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis","volume":"12","author":"Green","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102838","DOI":"10.1016\/j.jbc.2022.102838","article-title":"Regulation and function of the mammalian tricarboxylic acid cycle","volume":"299","author":"Arnold","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5577577","DOI":"10.1155\/2021\/5577577","article-title":"The regulatory role of \u03b1-ketoglutarate metabolism in macrophages","volume":"2021","author":"Liu","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100200","DOI":"10.1016\/j.advnut.2024.100200","article-title":"\u03b1-Ketoglutarate for preventing and managing intestinal epithelial dysfunction","volume":"15","author":"Du","year":"2024","journal-title":"Adv. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"801","DOI":"10.18632\/oncotarget.27486","article-title":"SLC25A32 sustains cancer cell proliferation by regulating flavin adenine nucleotide (FAD) metabolism","volume":"11","author":"Santoro","year":"2020","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3803\/EnM.2019.34.3.234","article-title":"Recent progress on branched-chain amino acids in obesity, diabetes, and beyond","volume":"34","author":"Siddik","year":"2019","journal-title":"Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Aguillard, A.M., and Tzeng, J. (2023). A cell-autonomous mechanism regulates BCAA catabolism in white adipocytes and systemic metabolic balance. bioRxiv.","DOI":"10.1101\/2023.07.31.551146"},{"key":"ref_27","first-page":"1090","article-title":"A systematic review of the role of renin-angiotensin-aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy","volume":"19","author":"Rahimi","year":"2014","journal-title":"Res. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.bbadis.2016.07.019","article-title":"The renin-angiotensin system, oxidative stress and mitochondrial function in obesity and insulin resistance","volume":"1863","author":"Ramalingam","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s10020-018-0044-3","article-title":"Reversal of angiotensin II-induced \u03b2-cell dedifferentiation via inhibition of NF-\u03baB signaling","volume":"24","author":"Chen","year":"2018","journal-title":"Mol. Med."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/5\/335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:27:13Z","timestamp":1779182833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/5\/335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["metabo16050335"],"URL":"https:\/\/doi.org\/10.3390\/metabo16050335","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}