71ccbbe3c3a04f4ce495bdba6798a8c9 ijms-27-00839.pdf 0b9a57bc6cf4b27f51fab141d19725e93330380d ijms-27-00839.pdf 16229e826fdac7139018f9ec66bf87cc10abf51d28962ecc9617c5adfd621d11 ijms-27-00839.pdf Title: Bariatric Surgery Reverses ORG and Exhibits a Distinct Transcriptomic Profile Compared to Weight Loss Through a Low-Fat Diet Subject: Weight loss is central to treating obesity-related kidney disease, yet the renal effects of a low-fat diet (LFD) versus bariatric surgery (BS) remain incompletely understood. This study compared their impact on obesity-related glomerulopathy (ORG). Twenty-eight male Wistar rats were fed a high-fat diet (HFD) for 10 weeks to induce obesity. Eight rats were sacrificed (the HFD group), eight switched to LFD for 10 weeks, and twelve underwent sleeve gastrectomy. Body weight, albuminuria, renal histology, and transcriptomic profiles were analyzed. Weight loss was modest in the LFD group (-1.6%) but substantial after BS (-13.2%), occurring 2.1 times faster. Albuminuria decreased in both interventions compared to HFD (LFD: 7228 514 ng/mL; BS: 6242 418 ng/mL; HFD: 10,384 1168 ng/mL; p < 0.01) and correlated strongly with weight loss (R2 = 0.78). The glomerular area was reduced in both groups, but only BS achieved complete histological resolution of ORG. Tubular cells in BS-treated rats showed megamitochondria and cristae disruption, while LFD induced milder alterations. Transcriptomics revealed suppression of mitochondrial maintenance genes and upregulation of oxidative stress and immunometabolic pathways. Immune-related genes upregulated in BS clustered into pro-inflammatory/chemotactic and regulatory modules. To the best of our knowledge, this is the first piece of evidence that BS fully reverses ORG, highlighting renal effects beyond weight loss alone. Keywords: obesity-related glomerulopathy; bariatric surgery; low-fat diet; obesity glomerulopathy reversion; transcriptomic changes; Wistar rats Author: Marina López-Martínez, Paula Rodríguez-Martínez, Lidia Blay, Pilar Armengol, Irina Pey, Mireia Ferrer, Esteban Porrini, Sergio Luis-Lima, Laura Díaz-Martín, Ana Elena Rodríguez-Rodríguez, Coriolano Cruz-Perera and Maruja Navarro-Díaz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Thu Jan 22 11:44:33 2026 CET ModDate: Thu Jan 22 11:50:07 2026 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 22080831 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ESGUOJ+URWPalladioL-Ital Type 1 Custom yes yes yes 123 0 FURYBE+URWPalladioL-Bold Type 1 Custom yes yes yes 124 0 COGLGI+CMSY10 Type 1 Builtin yes yes yes 125 0 AIRHKL+VnURWPalladioL Type 1 Custom yes yes yes 126 0 YMFXGE+URWPalladioL-Roma Type 1 Custom yes yes yes 127 0 HAPOHP+PalatinoLinotype TrueType WinAnsi yes yes no 214 0 HAPOHN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 215 0 HAPOHP+PalatinoLinotype TrueType WinAnsi yes yes no 221 0 HAPOHN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 222 0 OVNEXW+EURM10 Type 1 Builtin yes yes yes 303 0 HAPOHP+PalatinoLinotype TrueType WinAnsi yes yes no 240 0 HAPOHN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 241 0 HNZHFE+ArialMT TrueType WinAnsi yes yes no 447 0 MXMLXU+Arial-BoldMT TrueType WinAnsi yes yes no 446 0 HAPOHP+PalatinoLinotype TrueType WinAnsi yes yes no 298 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-03-13 04:27:15 CET RepresentationInformation: ijms-27-00839.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-03-12 18:41:18 CET Size: 22080831 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 679 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: Effects of Low-Fat Diet and Bariatric Surgery on Body Weight and Albuminuria in Wistar Rats Item: Title: Study of Renal Morphological Changes in LFD and BS Rats Item: Title: Treatment-Induced Transcriptomic Changes in Rat Kidneys Children: Item: Title: Kidney Transcriptomic Changes in the Comparison of LFD vs. HFD Groups Item: Title: Kidney Transcriptomic Changes in the Comparison of BS vs. HFD Groups Item: Title: Kidney Transcriptomic Changes in the Comparison of BS vs. LFD Groups Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Establishment of the Obesity-Induced Animal Model Item: Title: Bariatric Surgery Item: Title: Tissue and Sample Collection and Assessment of Albuminuria Item: Title: Morphometry, Histology, and Transmission Electron Microscopy (TEM) Item: Title: Total RNA Isolation Item: Title: Library Preparation, RNA Sequencing, and Data Analysis Item: Title: Gene Ontology and Pathway Analyses Item: Title: Statistical Analysis Item: Title: References Info: Title: Bariatric Surgery Reverses ORG and Exhibits a Distinct Transcriptomic Profile Compared to Weight Loss Through a Low-Fat Diet Author: Marina López-Martínez, Paula Rodríguez-Martínez, Lidia Blay, Pilar Armengol, Irina Pey, Mireia Ferrer, Esteban Porrini, Sergio Luis-Lima, Laura Díaz-Martín, Ana Elena Rodríguez-Rodríguez, Coriolano Cruz-Perera and Maruja Navarro-Díaz Subject: Weight loss is central to treating obesity-related kidney disease, yet the renal effects of a low-fat diet (LFD) versus bariatric surgery (BS) remain incompletely understood. This study compared their impact on obesity-related glomerulopathy (ORG). Twenty-eight male Wistar rats were fed a high-fat diet (HFD) for 10 weeks to induce obesity. Eight rats were sacrificed (the HFD group), eight switched to LFD for 10 weeks, and twelve underwent sleeve gastrectomy. Body weight, albuminuria, renal histology, and transcriptomic profiles were analyzed. Weight loss was modest in the LFD group (-1.6%) but substantial after BS (-13.2%), occurring 2.1 times faster. Albuminuria decreased in both interventions compared to HFD (LFD: 7228 514 ng/mL; BS: 6242 418 ng/mL; HFD: 10,384 1168 ng/mL; p < 0.01) and correlated strongly with weight loss (R2 = 0.78). The glomerular area was reduced in both groups, but only BS achieved complete histological resolution of ORG. Tubular cells in BS-treated rats showed megamitochondria and cristae disruption, while LFD induced milder alterations. Transcriptomics revealed suppression of mitochondrial maintenance genes and upregulation of oxidative stress and immunometabolic pathways. Immune-related genes upregulated in BS clustered into pro-inflammatory/chemotactic and regulatory modules. To the best of our knowledge, this is the first piece of evidence that BS fully reverses ORG, highlighting renal effects beyond weight loss alone. 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