Sofía Sanhueza1,2, Nicolás Tobar3, Mariana Cifuentes2, Daniela Quenti3, Rosaria Varì4, Beatrice Scazzocchio4, Roberta Masella4, Karin Herrera1,2, Adrián Paredes5, Glauco Morales5, Paulina Ormazabal6,7. 1. Institute of Health Sciences, Universidad de O'Higgins, Av. Libertador Bernardo O'Higgins 611, 2820000, Rancagua, Chile. 2. Laboratory of Obesity and Metabolism in Geriatrics and Adults (OMEGA), Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Av. El Líbano 5524, 7830490, Macul, Santiago, Chile. 3. Cellular and Molecular Biology Laboratory, Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Av. El Líbano 5524, 7830490, Macul, Santiago, Chile. 4. Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy. 5. Laboratorio de Química Biológica, Instituto Antofagasta (IA) and Departamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Av. Angamos 601, 1240000, Antofagasta, Chile. 6. Institute of Health Sciences, Universidad de O'Higgins, Av. Libertador Bernardo O'Higgins 611, 2820000, Rancagua, Chile. p.ormazabal@inta.uchile.cl. 7. Laboratory of Obesity and Metabolism in Geriatrics and Adults (OMEGA), Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Av. El Líbano 5524, 7830490, Macul, Santiago, Chile. p.ormazabal@inta.uchile.cl.
Abstract
BACKGROUND: Excess hepatic triglyceride (TG) accumulation (steatosis) commonly observed in obesity, may lead to non-alcoholic fatty liver disease (NAFLD). Altered regulation of intracellular lipid droplets (LD) and TG metabolism, as well as activation of JNK-mediated proinflammatory pathways may trigger liver steatosis-related disorders. Drosophila melanogaster is an animal model used for studying obesity and its associated disorders. In Drosophila, lipids and glycogen are stored in the fat body (FB), which resembles mammalian adipose tissue and liver. Dietary oversupply leads to obesity-related disorders, which are characterized by FB dysfunction. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Chile to counteract inflammatory diseases. Hydroethanolic extract of lampaya (HEL) contains considerable amounts of flavonoids that may explain its anti-inflammatory effect. METHODS: We studied whether HEL affects palmitic acid (PA, C16:0) and oleic acid (OA; C18:1)-induced TG accumulation and proinflammatory marker content in HepG2 hepatocytes as well as impaired lipid storage and proinflammatory molecule expression in Drosophila melanogaster fed a high-fat diet (HFD). RESULTS: In HepG2 hepatocytes, exposure to OA/PA elevated TG content, FABP4, ATGL and DGAT2 expression, and the JNK proinflammatory pathway, as well as TNF-α and IL-6 production, while diminished FAS expression. These effects were prevented by HEL co-treatment. In Drosophila larvae fed a HFD, HEL prevented TG accumulation and downregulated proinflammatory JNK pathway activation. CONCLUSION: HEL effect counteracting OA/PA- and HFD-induced lipid accumulation and proinflammatory marker expression in HepG2 hepatocytes and Drosophila larvae may represent a preventive approach against hepatic steatosis and inflammation, associated to obesity and NAFLD.
BACKGROUND: Excess hepatic triglyceride (TG) accumulation (steatosis) commonly observed in obesity, may lead to non-alcoholic fatty liver disease (NAFLD). Altered regulation of intracellular lipid droplets (LD) and TG metabolism, as well as activation of JNK-mediated proinflammatory pathways may trigger liver steatosis-related disorders. Drosophila melanogaster is an animal model used for studying obesity and its associated disorders. In Drosophila, lipids and glycogen are stored in the fat body (FB), which resembles mammalian adipose tissue and liver. Dietary oversupply leads to obesity-related disorders, which are characterized by FB dysfunction. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Chile to counteract inflammatory diseases. Hydroethanolic extract of lampaya (HEL) contains considerable amounts of flavonoids that may explain its anti-inflammatory effect. METHODS: We studied whether HEL affects palmitic acid (PA, C16:0) and oleic acid (OA; C18:1)-induced TG accumulation and proinflammatory marker content in HepG2 hepatocytes as well as impaired lipid storage and proinflammatory molecule expression in Drosophila melanogaster fed a high-fat diet (HFD). RESULTS: In HepG2 hepatocytes, exposure to OA/PA elevated TG content, FABP4, ATGL and DGAT2 expression, and the JNK proinflammatory pathway, as well as TNF-α and IL-6 production, while diminished FAS expression. These effects were prevented by HEL co-treatment. In Drosophila larvae fed a HFD, HEL prevented TG accumulation and downregulated proinflammatory JNK pathway activation. CONCLUSION: HEL effect counteracting OA/PA- and HFD-induced lipid accumulation and proinflammatory marker expression in HepG2 hepatocytes and Drosophila larvae may represent a preventive approach against hepatic steatosis and inflammation, associated to obesity and NAFLD.
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