Identification of D-Limonene Metabolites by LC-HRMS: An Exploratory Metabolic Switching Approach in a Mouse Model of Diet-Induced Obesity
José Fernando Rinaldi de Alvarenga,
Caroline Lei Preti,
Lara Santos Martins,
Guilherme Noronha Hernandez,
Brunna Genaro,
Bruna Lamesa Costa,
Caroline Gieseler Dias,
Eduardo Purgatto,
Jarlei Fiamoncini
Affiliations
José Fernando Rinaldi de Alvarenga
Human Nutrition Unit, Department of Food and Drug, University of Parma, 43125 Parma, Italy
Caroline Lei Preti
Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 580, São Paulo 05508-000, Brazil
Lara Santos Martins
Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 580, São Paulo 05508-000, Brazil
Guilherme Noronha Hernandez
Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 580, São Paulo 05508-000, Brazil
Brunna Genaro
Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 580, São Paulo 05508-000, Brazil
Bruna Lamesa Costa
Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 580, São Paulo 05508-000, Brazil
Caroline Gieseler Dias
Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Prof. Lineu Prestes 580, São Paulo 05508-000, Brazil
Eduardo Purgatto
Food Research Center (FoRC), University of São Paulo, Rua do Lago 250, São Paulo 05508-080, Brazil
Jarlei Fiamoncini
Food Research Center (FoRC), University of São Paulo, Rua do Lago 250, São Paulo 05508-080, Brazil
Metabolic switching has been raised as an important phenomenon to be studied in relation to xenobiotic metabolites, since the dose of the exposure determines the formation of metabolites and their bioactivity. Limonene is a monoterpene mostly found in citrus fruits with health activity, and its phase II metabolites and activity are still not clear. The aim of this work was to evaluate the effects of D-limonene in the development of diet-induced obesity in mice and to investigate metabolites that could be generated in a study assessing different doses of supplementation. Animals were induced to obesity and supplemented with 0.1% or 0.8% D-limonene added to the feed. Limonene phase I and II metabolites were identified in liver and urine by LC-ESI-qToF-MS/MS. To the best of our knowledge, in this study three new phase I metabolites and ten different phase II metabolites were first attributed to D-limonene. Supplementation with 0.1% D-limonene was associated with lower weight gain and a trend to lower accumulation of adipose tissue deposits. The metabolites limonene-8,9-diol, perillic acid and perillic acid-8,9-diol should be explored in future research as anti-obesogenic agents as they were the metabolites most abundant in the urine of mice that received 0.1% D-limonene in their feed.
