title: Bergamot polyphenol fraction prevents nonalcoholic fatty liver disease via stimulation of lipophagy in cafeteria diet-induced rat model of metabolic syndrome.
abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries. Defective autophagy of lipid droplets (LDs) in hepatocytes, also known as lipophagy, has recently been identified as a possible pathophysiological mechanism of NAFLD. Experimental and epidemiological evidence suggests that dietary polyphenols may prevent NAFLD. To address this hypothesis and analyze the underlying mechanisms, we supplemented bergamot polyphenol fraction (BPF) to cafeteria (CAF) diet-fed rats, a good model for pediatric metabolic syndrome and NAFLD. BPF treatment (50 mg/kg/day supplemented with drinking water, 3 months) potently counteracted the pathogenic increase of serum triglycerides and had moderate effects on blood glucose and obesity in this animal model. Importantly, BPF strongly reduced hepatic steatosis as documented by a significant decrease in total lipid content (-41.3% ± 12% S.E.M.), ultrasound examination and histological analysis of liver sections. The morphometric analysis of oil-red stained sections confirmed a dramatic reduction in LDs parameters such as total LD area (48.5% ± 15% S.E.M.) in hepatocytes from CAF+BPF rats. BPF-treated livers showed increased levels of LC3 and Beclin 1 and reduction of SQSTM1/p62, suggesting autophagy stimulation. Consistent with BPF stimulation of lipophagy, higher levels of LC3II were found in the LD subcellular fractions of BPF-expose livers. This study demonstrates that the liver and its lipid metabolism are the main targets of bergamot flavonoids, supporting the concept that supplementation of BPF is an effective strategy to prevent NAFLD.
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy; Interregional Research Center for Food Safety and Health, Catanzaro, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Parafati
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Lascala
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy.
authors.forename: Valeria Maria
authors.initials: VM
authors.lastname: Morittu
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Trimboli
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Graecia University, Campus Germaneto, Catanzaro, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Rizzuto
authors.affiliation: Department of Ecology, University of Calabria, Rende, Cosenza, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Brunelli
authors.affiliation: Department of Ecology, University of Calabria, Rende, Cosenza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Coscarelli
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Costa
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.affiliation: University of Colorado, Denver, CO, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ehrlich
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Isidoro
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy; Interregional Research Center for Food Safety and Health, Catanzaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.affiliation: Department of Health Sciences, Magna Graecia University, Campus Germaneto, Catanzaro, Italy; Interregional Research Center for Food Safety and Health, Catanzaro, Italy.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Janda
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D001343:Autophagy; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002957:Citrus / Q000737:chemistry*; D066273:Diet, Western / Q000009:adverse effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005638:Fruit / Q000737:chemistry; D006801:Humans; D007558:Italy; D066292:Lipid Droplets / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008082:Lipotropic Agents / Q000627:therapeutic use*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D024821:Metabolic Syndrome / Q000209:etiology / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000819:agonists / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D010936:Plant Extracts / Q000627:therapeutic use*; D059808:Polyphenols / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar; D014463:Ultrasonography
chemical_list: D019440:Anti-Obesity Agents; D015415:Biomarkers; D008082:Lipotropic Agents; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; D059808:Polyphenols; C526109:Anxa3 protein, rat
keywords: Dyslipidemia; Flavonoid; Hypercaloric diet; Lipid droplet fraction; Lipid macroautophagy; NAFLD