Use of Nanovesicles from Orange Juice to Reverse Diet-Induced Gut Modifications in Diet-Induced Obese Mice

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]-a and interleukin [IL]-1b), 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.

Plant Extracellular Vesicles and Nanovesicles: Focus on Secondary Metabolites, Proteins and Lipids with Perspectives on Their Potential and Sources

“…Current research regarding plant nanovesicles deals with general properties [ 3 , 12 , 13 , 14 ], host-versus-pathogen-interactions [ 8 , 11 , 15 , 16 , 17 ] and health-beneficial effects [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Another approach to use the advantageous properties of plant nanovesicles can be to foster the use of these small non-coding RNA (sRNA)-containing vehicles as bio-compatible and sustainable plant protection agents [ 25 ].…”

“…Although we have already learned a lot about properties and effects of vesicle subtypes isolated from distinct plant materials, we still neither know for sure how EVs pass through the apoplastic space or cell walls, nor what their function truly is. Considering the inhibitory effects of plant nanovesicles against pathogenic microorganisms and increased vesicle amounts after fungal infections in plants [ 8 , 10 , 11 , 17 , 25 ] together with the diversity of plant nanovesicle lipids [ 17 , 18 , 24 , 26 ], one can assume that plant cells produce EVs in order to control the growth of pathogenic microorganisms in case those try to invade the plant and also to address distant host cells, e.g., to improve their immune response. Taking into account that some pests mainly infect particular plants or plant families, it is plausible to imagine that not only the vesicle’s cargo is tuned by the host but also the envelope, to fight such pests as effectively as possible.…”

“…Lipid profiles have been shown to vary between different species and we therefore assume, so far, that lipid compositions are species-specific [ 17 ], although the extent of variations within the membrane composition in one and the same species remains unknown. Recent results by Berger et al, 2020 indicate that there might also be a family specificity [ 24 ]. Anyways, qualitative and quantitative differences of vesicle lipids can hypothetically be utilized to target particular cell types or organs.…”

“…Unfortunately, the few available data on this issue are ambiguous—on the one hand naringin, naringenin [ 30 ] and shogaol [ 22 ] were found in nanovesicles from grapefruit and ginger. On the other hand are the results of Berger et al, 2020, showing the absence of vitamin C and naringenin in orange nanovesicles [ 24 ]. To study the scope of nanovesicle-associated secondary metabolites, we investigated the presence of distinct characteristic alkaline and acidic constituents in nanovesicle-isolates from several pharmaceutically and toxicologically relevant herbal drugs.…”

Adipocyte-Derived Extracellular Vesicles: State of the Art

“…Alternatively, supplementation with EV from external sources might also contribute to restoring obesity-related WAT function and thereby modulate AdEV biological functions. For instance, we demonstrated that nanovesicles from orange juice could reverse high-fat-diet-induced gut modifications (e.g., length of villi and immune response) in diet-induced obese mice [ 96 ]. Additional investigations will be required to envisage diet and/or supplements as a strategy to modulate AdEV content in order to counteract their deleterious biological effects.…”