Opposing gastric and jejunal regulation of CELA2A in obesity and after Roux-en-Y gastric bypass suggests a role in gastrointestinal metabolic signaling.

AIMS: Roux-en-Y gastric bypass (RYGB) rapidly improves glycemic control in obesity and type 2 diabetes (T2D), but the underlying mechanisms remain incompletely understood. Chymotrypsin-like elastase family member 2A (CELA2A), a circulating pancreatic serine protease implicated in metabolic regulation, has been proposed to contribute to these effects, although its regulation in obesity and after metabolic surgery remains unclear. We investigated CELA2A expression in gastrointestinal tissues and circulation in relation to obesity and RYGB.

METHODS

Gastric biopsies were collected in a cross-cohort, non-paired comparison perioperatively from patients undergoing sleeve gastrectomy and postoperatively from patients after RYGB. Jejunal biopsies and serum samples were obtained in paired study setup before and after RYGB. Intestinal tissue and serum were also analyzed in mice fed a control or high-fat diet. CELA2A expression was assessed using Western blot, immunohistochemistry, and ELISA.

RESULTS

After RYGB, CELA2A expression increased in gastric mucosa but decreased in the jejunum, accompanied by reduced circulating CELA2A. Before surgery, jejunal CELA2A levels were positively associated with HbA1c, but not with fasting insulin. In high-fat diet-fed mice, jejunal CELA2A expression was increased, whereas gastric expression was reduced. Circulating CELA2A levels were not significantly altered in this model. In both species, CELA2A immunoreactivity was observed in mucosal glandular structures of the stomach and jejunum; however, detailed cellular localization in human tissue was not established, and circulating and tissue levels were not directly correlated.

CONCLUSION

CELA2A exhibits tissue-specific regulation in obesity and following bariatric surgery and may represent a candidate component of gastrointestinal metabolic signaling. Further studies are required to define its cellular origin and functional role in glucose homeostasis.