RESUMEN
Environmental pollutants, including polychlorinated biphenyls (PCBs), act as endocrine disruptors and impair various physiological processes. PCB 126 is associated with steatohepatitis, fibrosis, cirrhosis, and other hepatic injuries. These disorders can be regulated by microRNAs (miRNAs). Therefore, this study aimed to investigate the role of miRNAs in non-alcoholic fatty liver disease associated with exposure to PCB 126. Adult male C57BL/6 mice were exposed to PCB 126 (5 µmol/kg of body weight) for 10 weeks. The PCB group showed lipid accumulation in the liver in the presence of macro- and microvesicular steatosis and fibrosis with increased inflammatory and profibrotic gene expression, consistent with non-alcoholic steatohepatitis (NASH). PCB exposure also upregulated miR-155 and miR-34a, which induce the expression of proinflammatory cytokines and inflammation in the liver and reduce the expression of peroxisome proliferator-activated receptor α, which, in turn, impairs lipid oxidation and hepatic steatosis. Therefore, the present study showed that PCB 126 induced NASH via potential mechanisms involving miR-155 and miR-34a, which may contribute to the development of new diagnostic markers and therapeutic strategies.
Asunto(s)
Cirrosis Hepática , Ratones Endogámicos C57BL , MicroARNs , Bifenilos Policlorados , Regulación hacia Arriba , Animales , MicroARNs/genética , MicroARNs/metabolismo , Bifenilos Policlorados/toxicidad , Masculino , Ratones , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Regulación hacia Arriba/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Contaminantes Ambientales/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genéticaRESUMEN
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as morphofunctional changes in the liver. Studies have shown that Westernized eating patterns and environmental pollutants can directly induce the development of MASLD. This study evaluates the effect of co-exposure to interesterified palm oil (IPO) and 3,3',4,4',5-pentachlorobiphenyl (PCB-126) on the progression of MASLD in an animal model. C57BL/6 mice were fed IPO and co-exposed to PCB-126 for ten weeks. The co-exposure led to an imbalance in carbohydrate metabolism, increased systemic inflammation markers, and morphofunctional changes in the liver. These liver changes included the presence of inflammatory cells, fibrosis, alterations in aspartate transaminase (AST) and alanine transaminase (ALT) enzymes, and imbalance in gene expression related to fatty acid ß-oxidation, de novo lipogenesis, mitochondrial dynamics, and endoplasmic reticulum stress. Separate exposures to IPO and PCB-126 affected metabolism and MASLD progression. Nutritional and lifestyle factors may potentiate the onset and severity of MASLD.
Asunto(s)
Hígado , Ratones Endogámicos C57BL , Aceite de Palma , Bifenilos Policlorados , Animales , Bifenilos Policlorados/toxicidad , Ratones , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Contaminantes Ambientales/toxicidadRESUMEN
Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles.
Asunto(s)
Tejido Adiposo Blanco , Dieta Alta en Grasa , Inflamación , Ratones Endogámicos C57BL , Aceite de Palma , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Inflamación/metabolismo , Inflamación/inducido químicamente , Inflamación/patología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Masculino , Lipogénesis/efectos de los fármacos , Obesidad/metabolismo , Obesidad/etiología , Obesidad/inducido químicamente , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Insulina/sangre , Insulina/metabolismo , Resistencia a la InsulinaRESUMEN
The discovery of metabolically active brown adipose tissue (BAT) in human adults and the worldwide increase in obesity and obesity-related chronic noncommunicable diseases (NCDs) has made BAT a therapeutic target in the last two decades. The potential of BAT to oxidize fatty acids rapidly and increase energy expenditure inversely correlates with adiposity, insulin and glucose resistance, and cardiovascular and metabolic diseases. Currently, BAT is recognized by a new molecular signature; several BAT-derived molecules that act positively on target tissues have been identified and collectively called batokines. Bioactive compounds present in foods are endowed with thermogenic properties that increase BAT activation signaling. Understanding the mechanisms that lead to BAT activation and the batokines secreted by it within the thermogenic state is fundamental for its recruitment and management of obesity and NCDs. This review contributes to recent updates on the morphophysiology of BAT, its endocrine role in obesity, and the main bioactive compounds present in foods involved in classical and nonclassical thermogenic pathways activation.