Academic Journal
Metabolic surgery mitigates early kidney injury in obese youth with diabetes by suppressing mTORC1/JAK/STAT signaling
| Τίτλος: | Metabolic surgery mitigates early kidney injury in obese youth with diabetes by suppressing mTORC1/JAK/STAT signaling |
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| Συγγραφείς: | Naik, Abhijit S., Alakwaa, Fadhl M., Nair, Viji, McCown, Phillip J., Schaub, Jennifer A., Otto, Edgar A., Menon, Rajasree, Annese, Francesca, Choi, Ye Ji, Hampson, Hailey E., Inge, Thomas H., Hartman, John, Eddy, Sean, Smith, Cathy, Hodgin, Jeffrey B., Inoki, Ken, Srivastava, Swayam Prakash, Al-Fagih, Kareem, Yoshida, Shota, Goodrich, Jesse A., Cree, Melanie G., Narongkiatikhun, Phoom, Yuan, Long, Tommerdahl, Kalie L., Prasad, Pottumarthi, van Raalte, Daniël H., Kelsey, Megan M., Ryder, Justin R., Dobbs, Tyler J., Ladd, Patricia, Pennathur, Subramaniam, Nelson, Robert G., Okabayashi, Yusuke, Puelles, Victor G., Ferrence-Salo, Jenna, Beamish, Jeffrey A., Brosius, Frank C., Nadeau, Kristen J., Pyle, Laura, Kretzler, Matthias, Bjornstad, Petter |
| Πηγή: | Naik, A S, Alakwaa, F M, Nair, V, McCown, P J, Schaub, J A, Otto, E A, Menon, R, Annese, F, Choi, Y J, Hampson, H E, Inge, T H, Hartman, J, Eddy, S, Smith, C, Hodgin, J B, Inoki, K, Srivastava, S P, Al-Fagih, K, Yoshida, S, Goodrich, J A, Cree, M G, Narongkiatikhun, P, Yuan, L, Tommerdahl, K L, Prasad, P, van Raalte, D H, Kelsey, M M, Ryder, J R, Dobbs, T J, Ladd, P, Pennathur, S, Nelson, R G, Okabayashi, Y, Puelles, V G, Ferrence-Salo, J, Beamish, J A, Brosius, F C, Nadeau, K J, .... |
| Έτος έκδοσης: | 2026 |
| Συλλογή: | Aarhus University: Research |
| Θεματικοί όροι: | Chronic kidney disease, Diabetes, Metabolism, Nephrology, Obesity |
| Περιγραφή: | BACKGROUNDYouth with type 2 diabetes (T2D) and severe obesity face high risk of diabetic kidney disease, which metabolic bariatric surgery (MBS) can mitigate. This study explores structural and molecular changes in kidneys after vertical sleeve gastrectomy (VSG), a form of MBS.METHODSWe performed paired analyses, including metabolic profiling, kidney volume assessment, histological evaluation, and single-cell RNA sequencing (scRNA-seq), on kidney biopsies from 5 youth with T2D and obesity pre- and 12 months post-VSG in the IMPROVE-T2D (Impact of Metabolic surgery on Pancreatic, Renal and cardiOVascular hEalth in youth with T2D) cohort. Circulating proteomics with kidney transcriptomics were linked using data from an independent cohort of youth with obesity, with or without T2D, undergoing MBS in Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 64).RESULTSAfter VSG, participants lost weight and had improvements in insulin sensitivity and metabolic parameters. Kidney changes included reduced renal hyperfiltration, total kidney volume, mesangial matrix area, and microalbuminuria. scRNA-seq in proximal tubule (PT) and thick ascending limb cells indicated repression of glycolysis, gluconeogenesis, and tricarboxylic acid (TCA) cycle genes, with upregulation of AMP-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). Decreased metabolic signaling aligned with reduced ribosomal phosphorylated S6K (pS6K), suggesting attenuated mTORC1 activity. Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation in PT was diminished, correlating with lower circulating ligands from Teen-LABS proteomic data.CONCLUSIONMBS/VSG prompts kidney molecular adaptations, providing potential targets for nonsurgical interventions against obesity- and diabetes-associated kidney disease.FUNDINGUniversity of Washington with the American Diabetes Association, University of Michigan with Chan Zuckerberg Initiative, and Breakthrough T1D. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| ISSN: | 0021-9738 1558-8238 |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/41665972; info:eu-repo/semantics/altIdentifier/pissn/0021-9738; info:eu-repo/semantics/altIdentifier/eissn/1558-8238 |
| DOI: | 10.1172/JCI198545 |
| Διαθεσιμότητα: | https://pure.au.dk/portal/en/publications/1ccb809a-b6da-41c0-95a0-2ce64b486999 https://doi.org/10.1172/JCI198545 https://www.scopus.com/pages/publications/105034943591 |
| Rights: | info:eu-repo/semantics/openAccess |
| Αριθμός Καταχώρησης: | edsbas.774FEEB8 |
| Βάση Δεδομένων: | BASE |
| ISSN: | 00219738 15588238 |
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| DOI: | 10.1172/JCI198545 |