Pesce, Marcella (2022) Next-generation probiotics in obesity and metabolic syndrome: The effects of a genetically-modified lactobacillus paracasei producing oleoyl-ethanolamide (OEA) in obese mice. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Next-generation probiotics in obesity and metabolic syndrome: The effects of a genetically-modified lactobacillus paracasei producing oleoyl-ethanolamide (OEA) in obese mice. |
| Autori: | Autore Email Pesce, Marcella mapesc@hotmail.com |
| Data: | 13 Dicembre 2022 |
| Numero di pagine: | 95 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Clinica e Chirurgia |
| Dottorato: | Terapie avanzate biomediche e chirurgiche |
| Ciclo di dottorato: | 35 |
| Coordinatore del Corso di dottorato: | nome email Pane, Fabrizio fabrizio.pane@unina.it |
| Tutor: | nome email Sarnelli, Giovanni [non definito] |
| Data: | 13 Dicembre 2022 |
| Numero di pagine: | 95 |
| Parole chiave: | Engineered probiotics, oleoyl-ethanolamide, obesity |
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/12 - Gastroenterologia |
| Depositato il: | 06 Mar 2023 07:51 |
| Ultima modifica: | 09 Apr 2025 14:16 |
| URI: | http://www.fedoa.unina.it/id/eprint/14652 |
Abstract
Oleoylethanolamine (OEA) is an N-acylethanolamide produced on-demand by the enzyme N-acylphosphatidylethanolamine- preferring phospholipase D (NAPE-PLD). Being a key member of the larger family of bioactive autacoid local injury antagonist amides (ALIAmides), OEA displays a number of actions that are protective against obesity and related disorders, including the control of satiety and the regulation of the fat acids beta-oxidation in the adipose tissue. Despite its safety profile, however, high OEA doses are required in vivo to exert its therapeutic activity. To overcome OEA pharmacokinetic limitations, we developed a NAPE-PLD expressing Lactobacillus paracasei F19 (pNAPE-LP) able to produce OEA under the boost of ultra-low (and non-toxic) oleate supply. We tested this formulation in obese mice treated with high-fat diet (HFD), investigating the effects of pNAPE-LP + oleate on weight, glycemic and lipid profile and on histological severity of liver steatosis. Moreover, we evaluated the effects of pNAPE-LP and oleate on gut microbiome composition. The coadministration of pNAPE-LP and oleate led to time-and palmitate-concentration dependent release of OEA, resulting in a significant weight loss in HFD treated mice, with a parallel improvement in blood glucose and lipid levels and significant improvement in liver steatosis. Furthermore, at the end of the treatment, microbiome analysis revealed a restore in the imbalance between Firmicutes and Bacteroidetes ratio with an increased abundance for the strains Lactobacillus and Prevotella species. These effects were strictly dependent on the ability of pNAPE-LP of integrating within the host microbiota and release the biotherapeutic in situ, since we did not observe any effects with the treatment with the native probiotic. pNAPE-LP combined with ultra-low oleate supply stands as a new method to increase the in situ intestinal delivery of OEA as a new therapeutic in weight control and metabolic syndrome.
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