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Use of Nanovesicles from Orange Juice to Reverse Diet-Induced Gut Modifications in Diet-Induced Obese Mice
Emmanuelle Berger1, Pascal Colosetti1, Audrey Jalabert1
1CarMeN Laboratory (INRAe U1397, INSERM U1060, Lyon 1 University, INSA Lyon), Bâtiment CENS ELI-2D, Pierre-Bénite, France.
Abstract:
We have determined whether orange juice-derived nanovesicles (ONVs) could be used for the treatment of obesity-associated intestinal complications. ONVs were characterized by lipidomic, metabolomic, electron microscopy. In vitro, intestinal barriers (IBs = Caco-2+HT-29-MTX) were treated with ONVs and co-cultured with adipocytes to monitor IB fat release. In vivo, obesity was induced with a high-fat, high-sucrose diet (HFHSD mice) for 12 weeks. Then, half of HFHSD mice were gavaged with ONVs. One-month ONV treatment did not modify HFHSD-induced insulin resistance but reversed diet-induced gut modifications. In the jejunum, ONVs increased villi size, reduced triglyceride content, and modulated mRNA levels of genes involved in immune response (tumor necrosis factor [TNF]-α and interleukin [IL]-1β), barrier permeability (CLDN1, OCLN, ZO1), fat absorption, and chylomicron release. ONVs targeted microsomal triglyceride transfer protein (MTP) and angiopoietin-like protein-4 (ANGPTL4), two therapeutic targets to reduce plasma lipids and inflammation in gastrointestinal diseases. Interestingly, ONV treatment did not aggravate liver steatosis, as MTP mRNA was increased in the liver. Therefore, ONVs protected both intestine and the liver from fat overload associated with the HFHSD. As ONVs concentrated amino acids and bioactive lipids versus orange juice, which are deficient in obese patients, the use of ONVs as a dietary supplement could bring physiological relevant compounds in the jejunum to accelerate the restoration of intestinal functions during weight loss in obese patients.
Insights
Orange juice-derived nanovesicles (ONVs) reversed gut damage in obese mice. ONVs improved intestinal function and protected the intestine and liver from fat overload, aiding recovery during weight loss.
Area of Science:
- Nutritional science and gastroenterology
- Nanomedicine and drug delivery
- Metabolic disease research
Background:
- Obesity is linked to intestinal complications and metabolic dysfunction.
- Dietary interventions are crucial for managing obesity-associated gut issues.
- Orange juice-derived nanovesicles (ONVs) show potential for therapeutic applications.
Purpose of the Study:
- To investigate the efficacy of ONVs in treating obesity-related intestinal complications.
- To evaluate the impact of ONVs on gut barrier function, fat absorption, and inflammation.
- To assess ONVs' effects on liver steatosis in a diet-induced obesity model.
Main Methods:
- Characterization of ONVs using lipidomics, metabolomics, and electron microscopy.
- In vitro studies with intestinal barrier models and adipocytes.
- In vivo studies using a high-fat, high-sucrose diet (HFHSD) induced obesity mouse model, followed by ONV gavage.
- Analysis of jejunal and liver tissues for histological changes, gene expression, and triglyceride content.
Main Results:
- ONV treatment reversed diet-induced gut modifications in HFHSD mice.
- ONVs increased jejunal villi size and reduced triglyceride content.
- ONVs modulated genes involved in immune response, barrier permeability, and fat absorption, targeting MTP and ANGPTL4.
- ONV treatment protected the intestine and liver from fat overload without aggravating liver steatosis.
Conclusions:
- ONVs demonstrate protective effects on the intestine and liver in obesity.
- ONVs may accelerate the restoration of intestinal functions during weight loss in obese individuals.
- ONVs, as a dietary supplement, can deliver beneficial compounds to the jejunum, addressing deficiencies in obese patients.
