Bariatric surgery reverses ORG and exhibits a distinct transcriptomic profiel compared to weight loss through a low-fat diet

Weight loss is central to treating obesity-related kidney disease, yet the renal effects of 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 (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: 10384 ± 1168 ng/mL; p < 0.01) and correlated strongly with weight loss (R² = 0.78). 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 immunometabolism 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 evidence that BS fully reverses ORG, highlighting renal effects beyond weight loss alone. Overall design: Twenty-eight Wistar rats were first fed a high-fat diet for 10 weeks to induce obesity. They were then divided into three groups: an obese control (HFD group), a low-fat diet (LFD) group, and a bariatric surgery (BS) group, all evaluated for weight, albuminuria, kidney histology, and transcriptomics. Raw data for the the HFD samples are available under PRJNA1092068 (GSE262503).