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Updated: Jan 30, 2026

A Murine Model of Vertical Sleeve Gastrectomy
Published on: December 18, 2017
Oea Signaling Pathways and the Metabolic Benefits of Vertical Sleeve Gastrectomy
Chelsea R Hutch1, Danielle R Trakimas2, Karen Roelofs1
1University of Michigan, Ann Arbor, MI.
Objective:
The aim of this study was to determine whether downstream [peroxisome proliferator-activated-receptor alpha (PPARα) and the G-protein coupled receptor, GPR119] and upstream (a fatty acid translocase, CD36) signaling targets of N-oleoylethanolamide (OEA) were necessary for weight loss, metabolic improvements, and diet preference following vertical sleeve gastrectomy (VSG).
Summary Background Data:
OEA is an anorectic N-acylethanolamine produced from dietary fats within the intestinal lumen that can modulate lipid metabolism, insulin secretion, and energy expenditure by activating targets such as PPARα and GPR119.
Methods:
Diet-induced obese mice, including wild-type or whole body knockout (KO) of PPARα, GPR119, and CD36, were stratified to either VSG or sham surgery before body weight, body composition, diet preference, and glucose and lipid metabolic endpoints were assessed.
Results:
We found increased duodenal production of OEA and expression of both GPR119 and CD36 were upregulated in wild-type mice after VSG. However, weight loss and glucose tolerance were improved in response to VSG in PPARαKO, GPR119KO, and CD36KO mice. In fact, VSG corrected hepatic triglyceride dysregulation in CD36KO mice, and circulating triglyceride and cholesterol levels in PPARαKO mice. Lastly, we found PPARα-mediated signaling contributes to macronutrient preference independent of VSG, while removal of CD36 signaling blunts the VSG-induced shift toward carbohydrate preference.
Conclusions:
In the search for more effective and less invasive therapies to help reverse the global acceleration of obesity and obesity-related disease OEA is a promising candidate; however, our data indicate that it is not an underlying mechanism of the effectiveness of VSG.
Insights
Vertical sleeve gastrectomy (VSG) improves weight loss and metabolism independently of N-oleoylethanolamide (OEA) signaling targets like PPARα, GPR119, and CD36. VSG
Area of Science:
- Bariatric Surgery
- Metabolic Disease Research
- Obesity Pathophysiology
Background:
- N-oleoylethanolamide (OEA) is an anorectic compound influencing lipid metabolism and energy expenditure.
- OEA activates signaling targets including peroxisome proliferator-activated-receptor alpha (PPARα), GPR119, and CD36.
- Obesity and related diseases represent a significant global health challenge.
Purpose of the Study:
- To investigate if key signaling targets of N-oleoylethanolamide (OEA) are essential for weight loss and metabolic improvements after vertical sleeve gastrectomy (VSG).
- To determine the role of PPARα, GPR119, and CD36 in mediating the effects of VSG on body weight, composition, and diet preference.
Main Methods:
- Diet-induced obese mice with genetic knockouts (KO) for PPARα, GPR119, and CD36 underwent either VSG or sham surgery.
- Evaluated body weight, body composition, diet preference, and metabolic parameters (glucose tolerance, lipid profiles).
- Assessed duodenal OEA production and target gene expression post-surgery.
Main Results:
- VSG enhanced weight loss and glucose tolerance in wild-type and all knockout mouse models (PPARαKO, GPR119KO, CD36KO).
- VSG corrected hepatic triglyceride dysregulation in CD36KO mice and improved lipid profiles in PPARαKO mice.
- PPARα signaling influenced macronutrient preference independently of VSG, while CD36 absence blunted the VSG-induced shift towards carbohydrates.
Conclusions:
- The effectiveness of VSG in promoting weight loss and metabolic improvements does not rely on the N-oleoylethanolamide (OEA) signaling pathway.
- While OEA is a potential therapeutic candidate for obesity, it is not the mechanism driving VSG's success.
- Understanding these pathways can inform future obesity treatment strategies.
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