Gastrectomy promoted diabetes remission involves the molecular clock and epigenetic mechanisms in a rat model of lean type 2 diabetes

Sep 29, 2026

Uploaded by Asher

Gastrectomy promoted diabetes remission is investigated in a lean type 2 diabetes rat model to uncover molecular and regulatory mechanisms. After vertical sleeve gastrectomy, hyperglycemia decreased persistently along with shifts in nycthemeral feeding patterns and activity. Liver transcriptome and lipidome analyses indicate remodeling of inflammatory, PPAR signalling, and fatty-acid metabolism pathways, including phosphatidylcholine and lysophosphatidylethanolamine regulation. Deeper analysis links changes in histone methylation and coordinated transcription of core circadian clock regulators. Results support chronobiology and epigenetic contributions to long-term therapeutic outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Background

Role of bariatric surgery in type 2 diabetes remission

Need to clarify mechanisms beyond weight loss

Methods and model

Goto-Kakizaki rat model and surgical interventions

Multilevel molecular profiling

Key findings

Metabolic and behavioral effects after VSG

Liver transcriptome and lipidome pathway changes

Molecular clock gene regulation and epigenetic signatures

Interpretation and implications

Chronobiology and epigenetic mechanisms in remission

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Gastrectomy promoted diabetes remission involves the molecular clock and epigenetic mechanisms ina rat model of lean type 2 diabetes Aurélie Le Lay1,10, François Brial2,10, Claude Rouch1, Xiaojian Shao3,4, Mathieu Bourgey3, Kazuhiro Sonomura5,6, Huiting Ou6, Sara Ghezzal1, Mylène Vincent1, Marylène Rugard7, KarineAudouze7, Jiannis Ragoussis3, Fumihiko Matsuda6, Guillaume Bourque3, Elin Grundberg3,8,9, Mark Lathrop3, Christophe Magnan1 & Dominique Gauguier1,3,6􀀍 Bariatric surgery results in type 2 diabetes (T2D) improvement. To identify mechanisms associated with gastrectomy-promoted T2D remission in lean individuals, we performed pathophysiological, behavioural and molecular (liver transcriptome, metabolome and lipidome) investigations in the Goto-Kakizaki (GK) model of spontaneously-occurring non-obeseT2D following vertical sleeve gastrectomy (VSG) or sham operation. VSG resulted in sustained reduction in hyperglycemia and changes in nycthemeral feeding patterns and activity. Liver transcriptome and lipidome profiling pointed to changes in the expression of genes involved in inflammation, PPAR signalling and fatty acid metabolism, and in the regulation of phosphatidylcholine and lysophosphatidylethanolamine classes. Deeper analysis revealed altered expression of genes involved in histone methylation and coordinately differential transcription of key regulators ofthe molecular clock (Clock, Arntl/Bmal1, Per1, Per2, Per3). In addition to previously reported changes in bile acid metabolism and gut microbiome in this model ofVSG, our findings underline the multiple biological mechanisms associated with diabetes remission following VSG and suggest a contribution of chronobiology and epigenetic processes in the long-term therapeutic consequences of VSG in the context of polygenic non-obeseT2D. Keywords Epigenome, Goto-Kakizaki rat, Bariatric surgery, Circadian clock, Lipidome, Metabolome, Transcriptome Type 2 diabetes (T2D) and obesity are characterised by an etiology combining both environmental influencesand genetic risk factors1. Bariatric surgery, which is routinely used in obese patients, results in sustained weight loss2,3 but also in improved glucose homeostasis, through mechanisms that are at least in part independent of weight loss and reduced caloric intake4. Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG) and stomach sparing protocols (e.g. duodenal-jejunal and jejuno-ileal bypass, jejunectomy) have consistently demonstrated their beneficial role in T2D patients5, but the biological processes involved remain poorly understood. Changes in the microbiome architecture and bile acids, improved insulin sensitivity and restored β-cell mass and function mediated by incretins, including the glucagon like peptide (GLP1), collectively account for instances ofT2D remission after bariatric surgery6. However, the combination of obesity and T2D in patients 1Functional and Adaptive Biology Unit, CNRS UMR 8251, University Paris Cité, 4 Rue Marie Andrée Lagroua WeillHalle, 75013 Paris, France. 2INSERM U1132 Biologie de L’os Et du Cartilage (BIOSCAR), University Paris Cité, 75010 Paris, France. 3Victor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, 740 Doctor Penfield Avenue, Montreal, QC H3A 0G1, Canada. 4Digital Technologies Research Centre, National Research Council Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada. 5Life Science Research Center, Technology Research Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan. 6Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. 7University Paris Cité, INSERM UMR 1124, 45 Rue Des Saint-Pères, 75006 Paris, France. 8Department of Pediatrics, University of Missouri-Kansas City School of Medicine, 2411 Holmes Street, Kansas City, MO 64108, USA. 9Genomic Medicine Center, Children’s Mercy Kansas City, 2401 Gillham Ro

FAQs

What is the study trying to explain about gastrectomy and diabetes remission?

The study aims to identify biological mechanisms associated with gastrectomy-promoted type 2 diabetes remission in lean individuals, focusing on molecular and regulatory pathways.

What changes were observed in the rat model after vertical sleeve gastrectomy?

Vertical sleeve gastrectomy led to sustained reduction in hyperglycemia and altered nycthemeral feeding patterns and activity.

Which molecular systems were implicated by liver transcriptome and lipidome profiling?

The analyses pointed to changes in genes involved in inflammation, PPAR signalling, and fatty-acid metabolism, as well as regulation of phosphatidylcholine and lysophosphatidylethanolamine classes, alongside altered histone methylation and coordinated transcription of circadian clock regulators.

Sep 29, 2026

Uploaded by Asher