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Updated: Mar 14, 2026
Roux-en-Y Gastric Bypass Operation in Rats
Published on: June 11, 2012
Roux-en-Y gastric bypass surgery is effective in fibroblast growth factor-21 deficient mice
Christopher D Morrison1, Zheng Hao1, Michael B Mumphrey1
1Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Objective:
The mechanisms by which bariatric surgeries so effectively and lastingly reduce body weight and normalize metabolic dysfunction are not well understood. Fibroblast growth fator-21 (FGF21) is a key regulator of metabolism and is currently considered for treatment of obesity. Although elevated by acute food deprivation, it is downregulated after weight loss induced by chronic calorie restriction but not after Roux-en-Y gastric bypass surgery. Therefore, the goal of the present study was to assess the role of FGF21-signaling in the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB).
Methods:
High-fat diet-induced obese FGF21-deficient (FGF21(-/-)) and wildtype (WT) mice were subjected to RYGB, sham surgery, or caloric restriction to match body weight of RYGB mice. Body weight, body composition, food intake, energy expenditure, glucose tolerance, and insulin sensitivity, as well as plasma levels and hepatic mRNA expression of FGF21 were measured.
Results:
Hepatic expression and plasma levels of FGF21 are higher after RYGB compared with similar weight loss induced by caloric restriction, suggesting that elevated FGF21 might play a role in preventing increased hunger and weight regain after RYGB. However, although the body weight differential between RYGB and sham surgery was significantly reduced in FGF21(-/-) mice, RYGB induced similarly sustained body weight and fat mass loss, initial reduction of food intake, increased energy expenditure, and improvements in glycemic control in FGF21(-/-) and WT mice.
Conclusions:
FGF21 signaling is not a critical single factor for the beneficial metabolic effects of RYGB. This may open up the possibility to use FGF21 as adjuvant therapy in patients with ineffective bariatric surgeries.
Insights
Fibroblast growth factor-21 (FGF21) is not essential for Roux-en-Y gastric bypass (RYGB) surgery
Area of Science:
- Metabolic surgery
- Obesity research
- Endocrinology
Background:
- Bariatric surgeries effectively reduce body weight and metabolic dysfunction, but mechanisms remain unclear.
- Fibroblast growth factor-21 (FGF21) is a key metabolic regulator, with potential therapeutic applications for obesity.
- FGF21 levels differ after weight loss induced by calorie restriction versus Roux-en-Y gastric bypass (RYGB) surgery.
Purpose of the Study:
- To investigate the role of FGF21 signaling in the metabolic benefits of RYGB.
- To compare the effects of RYGB with caloric restriction in FGF21-deficient mice.
Main Methods:
- Obese mice lacking FGF21 (FGF21(-/-)) and wildtype (WT) mice underwent RYGB, sham surgery, or caloric restriction.
- Evaluated body weight, composition, food intake, energy expenditure, glucose tolerance, and insulin sensitivity.
- Measured plasma FGF21 levels and hepatic FGF21 mRNA expression.
Main Results:
- RYGB led to higher hepatic FGF21 expression and plasma levels compared to caloric restriction.
- Despite a reduced weight differential in FGF21(-/-) mice, RYGB produced similar sustained weight loss, fat mass reduction, and metabolic improvements in both FGF21(-/-) and WT mice.
- RYGB also resulted in initial food intake reduction and increased energy expenditure in both groups.
Conclusions:
- FGF21 signaling is not a critical determinant for the beneficial metabolic effects of RYGB.
- These findings suggest FGF21 could be explored as an adjuvant therapy for patients with suboptimal responses to bariatric surgery.
