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Objective <p>Roux-en-Y gastric bypass (RYGB) is a highly effective therapy for obesity and type 2 diabetes mellitus (T2DM), but its underlying mechanisms, particularly regarding adipose tissue remodeling, remain incompletely understood. This study investigated the hypothesis that RYGB induces a phenotypic shift in white adipose tissue (WAT) towards a brown-like (beige) state, which contributes to its systemic metabolic benefits.</p> Methods <p>An obese T2DM model was established in C57BL/6J mice using a high-fat diet and low-dose streptozotocin. Mice were allocated to control (CON), sham-operated (SHAM), or RYGB groups. Metabolic parameters were monitored for 8 weeks post-surgery. Terminal analyses included body composition assessment via micro-CT, plasma lipid profiling, and histological evaluation of liver and multiple adipose depots (epididymal, inguinal, perirenal, and brown adipose tissue).</p> Results <p>RYGB induced sustained weight loss, normalized glycemia, improved insulin sensitivity, and corrected dyslipidemia. Body composition analysis revealed a preferential reduction in visceral and subcutaneous fat mass, with lean mass preserved. Histologically, RYGB markedly alleviated hepatic steatosis. Crucially, RYGB induced a profound remodeling of WAT, characterized by a significant reduction in adipocyte size in both epididymal and inguinal depots, indicating improved adipose tissue health. Concomitantly, brown adipose tissue exhibited a reversal of obesity-associated “whitening,” displaying a more active morphology with smaller lipid droplets.</p> Conclusion <p>Beyond its established effects on weight and metabolism, RYGB induces morphological changes in white adipose tissue consistent with improved metabolic health. This structural and phenotypic reprogramming of fat depots likely represents a key cellular mechanism underpinning the surgery’s potent anti-diabetic and hepatoprotective effects. Our findings highlight adipose tissue plasticity as a central therapeutic target of RYGB.</p> Clinical trial number <p>Not applicable.</p>

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Roux-en-Y gastric bypass promotes white adipose tissue browning and systemic metabolic recovery in obese type 2 diabetic mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Tengfei Qi,
  • Ru Ji,
  • Liangping Wu,
  • Jipei He,
  • Hongbin Zhang,
  • Zhengyong Xie

摘要

Objective

Roux-en-Y gastric bypass (RYGB) is a highly effective therapy for obesity and type 2 diabetes mellitus (T2DM), but its underlying mechanisms, particularly regarding adipose tissue remodeling, remain incompletely understood. This study investigated the hypothesis that RYGB induces a phenotypic shift in white adipose tissue (WAT) towards a brown-like (beige) state, which contributes to its systemic metabolic benefits.

Methods

An obese T2DM model was established in C57BL/6J mice using a high-fat diet and low-dose streptozotocin. Mice were allocated to control (CON), sham-operated (SHAM), or RYGB groups. Metabolic parameters were monitored for 8 weeks post-surgery. Terminal analyses included body composition assessment via micro-CT, plasma lipid profiling, and histological evaluation of liver and multiple adipose depots (epididymal, inguinal, perirenal, and brown adipose tissue).

Results

RYGB induced sustained weight loss, normalized glycemia, improved insulin sensitivity, and corrected dyslipidemia. Body composition analysis revealed a preferential reduction in visceral and subcutaneous fat mass, with lean mass preserved. Histologically, RYGB markedly alleviated hepatic steatosis. Crucially, RYGB induced a profound remodeling of WAT, characterized by a significant reduction in adipocyte size in both epididymal and inguinal depots, indicating improved adipose tissue health. Concomitantly, brown adipose tissue exhibited a reversal of obesity-associated “whitening,” displaying a more active morphology with smaller lipid droplets.

Conclusion

Beyond its established effects on weight and metabolism, RYGB induces morphological changes in white adipose tissue consistent with improved metabolic health. This structural and phenotypic reprogramming of fat depots likely represents a key cellular mechanism underpinning the surgery’s potent anti-diabetic and hepatoprotective effects. Our findings highlight adipose tissue plasticity as a central therapeutic target of RYGB.

Clinical trial number

Not applicable.