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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.
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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
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.
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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
AIM: To evaluate the effects of PPARα and PPARγ activation (alone or in combination) on the gut-liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. METHODS: Male C57BL/6J were fed a control diet (C) or a high-fat diet (HF) for ten weeks. Then, a four-week treatment started: HF-α (WY14643), HF-γ (low-dose pioglitazone), and HF-αγ (combination). RESULTS: The HF caused overweight, insulin resistance, impaired gut-liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta-oxidation genes, reducing macrophage infiltration and steatosis in the liver. CONCLUSION: Treatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolic-associated fatty liver disease treatment.
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Dieta Alta en Grasa , Enfermedad del Hígado Graso no Alcohólico , Masculino , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , PPAR alfa/genética , PPAR alfa/metabolismo , Obesidad/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismoRESUMEN
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.
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Tejido Adiposo Pardo , Obesidad , Humanos , Tejido Adiposo Pardo/metabolismo , Obesidad/metabolismo , Metabolismo Energético , Glucosa/metabolismo , Transducción de Señal , Termogénesis , Adipocitos Marrones/metabolismoRESUMEN
Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.
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Bertholletia , Microbioma Gastrointestinal , Insuficiencia Renal Crónica , Ratas , Animales , Dieta , Neuroglía/metabolismo , Insuficiencia Renal Crónica/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to investigate the role of peroxisome proliferator-activated receptor (PPAR) activation (single PPARα or PPARγ, and dual PPARα/γ) on UCP1-dependent and -independent thermogenic pathways and mitochondrial metabolism in the subcutaneous white adipose tissue of mice fed a high-fat diet. METHODS: Male C57BL/6 mice received either a control diet (10% lipids) or a high-fat diet (HF; 50% lipids) for 12 wk. The HF group was divided to receive the treatments for 4 wk: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg). RESULTS: The HF group was overweight, insulin resistant, and had subcutaneous white adipocyte dysfunction. Treatment with PPARα and PPARα/γ reduced body mass, mitigated insulin resistance, and induced browning with increased UCP1-dependent and -independent thermogenesis activation and improved mitochondrial metabolism to support the beige adipocyte phenotype. CONCLUSION: PPARα and dual PPARα/γ activation recruited UCP1+ beige adipocytes and favored UCP1-independent thermogenesis, yielding body mass and insulin sensitivity normalization. Preserved mitochondrial metabolism emerges as a potential target for obesity treatment using PPAR agonists, with possible clinical applications.
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Adipocitos Beige , Resistencia a la Insulina , Animales , Masculino , Ratones , Adipocitos Beige/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Dieta Alta en Grasa/efectos adversos , Lípidos , Ratones Endogámicos C57BL , Dinámicas Mitocondriales , PPAR alfa/metabolismo , Termogénesis , Proteína Desacopladora 1/metabolismoRESUMEN
This study aimed to evaluate the preventive and therapeutic effects of coffee consumption on molecular changes and adipose tissue remodeling in a murine model of high-fat diet-induced obesity. Three-month-old C57BL/6 mice were initially divided into three groups, namely, control (C), high-fat (HF), and coffee prevention (HF-CP) groups, and the HF group was subdivided at the end of the 10th week into two subgroups, an HF group and a coffee treatment (HF-CT) group; thus, a total of four groups were investigated at the 14th week of the experiment. The HF-CP group had lower body mass than the HF group (-7%, P < .05) and a better distribution of adipose tissue. Both groups that received coffee (HF-CP and HF-CT) showed improved glucose metabolism compared with the HF group. Coffee consumption also attenuated adipose tissue inflammation and showed decreased macrophage infiltration and lower IL-6 levels compared with the HF group (HF-CP: -337% %, P < .05; HF-CT: -275%, P < .05). Hepatic steatosis and inflammation were attenuated in the HF-CP and HF-CT groups. The HF-CP group showed more pronounced expression of genes involved in adaptive thermogenesis and mitochondrial biogenesis (PPARγ, Prdm16, Pcg1α, ß3-adrenergic receptor, Ucp-1, and Opa-1) than the other experimental groups. Preventive coffee consumption associated with a high-fat diet ameliorates the metabolic profile related to the development of obesity and its comorbidities.
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Tejido Adiposo Pardo , Dieta Alta en Grasa , Ratones , Animales , Tejido Adiposo Pardo/metabolismo , Dieta Alta en Grasa/efectos adversos , Café , Ratones Endogámicos C57BL , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Inflamación/metabolismoRESUMEN
AIM: To evaluate the effects of single PPARα or PPARγ activation, and their synergism (combined PPARα/γ activation) upon the gut-adipose tissue axis, focusing on the endotoxemia and upstream interscapular brown adipose tissue (iBAT) function in high-saturated fat-fed mice. METHODS: Male C57BL/6 mice received a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for 12 weeks. Then, the HF group was divided to receive the treatments for four weeks: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg). RESULTS: The HF group exhibited overweight, oral glucose intolerance, gut dysbiosis, altered gut permeability, and endotoxemia, culminating in iBAT whitening. The downregulation of LPS-Tlr4 signaling underpinned reduced inflammation and improved lipid metabolism in iBAT in the HFα/γ group, the unique to show normalized body mass and increased energy expenditure. CONCLUSION: PPARα/γ synergism treated obesity by ameliorating the gut-adipose tissue axis, where restored gut microbiota and permeability controlled endotoxemia and rescued iBAT whitening through favored thermogenesis.
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Endotoxemia , PPAR alfa , Animales , Masculino , Ratones , Tejido Adiposo Pardo/metabolismo , Dieta Alta en Grasa , Lípidos , Ratones Endogámicos C57BL , Obesidad/metabolismo , PPAR alfa/metabolismo , PPAR gamma/metabolismoRESUMEN
Despite advances in diagnosis and therapy, breast cancer remains the leading cause of death in many countries. Green tea (GT) has been proposed to play a crucial role in cancer chemoprevention. Although extensive research has been conducted on GT phytochemicals, most experimental studies concentrate mainly on commercial formulations or isolated catechins. This study presents a comparative investigation into the anticancer properties of green tea extract (GTE) and epigallocatechin-3-gallate (EGCG) in a three-dimensional (3D) MCF-7 breast cancer cell culture. MCF-7 spheroids were exposed to GTE or EGCG, and effects on 3D culture formation, growth, cell viability, and migration were examined. GTE inhibits cell migration and the formation of breast cancer spheroids more effectively than EGCG, while inducing more pronounced morphological changes in the spheroids' structure. These findings suggest that the food matrix improves GTE effects on breast cancer spheroids, supporting the hypothesis that a mixture of phytochemicals might enhance its anticancer potential.
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The main goal of this study was to evaluate the reno-protective effects of a phenolic-rich Açaí seed extract (ASE) in mice with kidney failure. Kidney failure was induced chemically with an adenine-rich diet (0.25% w/w for 4 weeks) in male CD1 Swiss mice. Mice were then provided daily with ASE (at a dose of ~ 350 mg/kg/day) in drinking water for 4 weeks. Adenine mice exhibited renal dysfunction evidenced by increased proteinuria, increased uremia, extensive tubular atrophy and kidney fibrosis associated with overexpression of pro-fibrotic genes (collagen 1a1, transforming growth factor ß1, TGF-ß1) and markers of tubular injury (such as Kidney injury molecule-1, KIM-1). ASE was able to beneficially counteract all these effects. ASE improved oxidative damage and fibrosis by decreasing carbonylated protein and MDA concentrations, as well as collagen deposition in renal tissue. ASE decreased the expression of TGF-ß1 gene and the abundance of protein TGF-ß1 in kidneys. It further decreased both expression and urinary excretion of tubular injury biomarkers, e.g., KIM-1 and Neutrophil gelatinase-associated lipocalin. CKD ASE-treated mice exhibited higher polyphenol content and total antioxidant capacity compared to control mice. ASE further prevented the expression of profibrotic genes in HK2 human tubular cells exposed to uremic toxins. Taken together, these findings suggest that ASE exerted potent reno-protective and anti-fibrotic effects through its antioxidant activity and the modulation of the TGF-ß1 pathway.
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Polifenoles , Insuficiencia Renal , Humanos , Masculino , Ratones , Animales , Polifenoles/farmacología , Factor de Crecimiento Transformador beta1/genética , Riñón , Antioxidantes/farmacología , Adenina , Fibrosis , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: Obesity and comorbidities onset encompass gut dysbiosis, altered intestinal permeability, and endotoxemia. Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease (NAFLD) management. Peroxisome proliferator-activated receptor (PPAR)-alpha activation and dipeptidyl-peptidase-4 (DPP-4) inhibition alleviate NAFLD, but the mechanism may involve gut microbiota modulation and merits further investigation. AIM: To address the effects of PPAR-alpha activation and DPP-4 inhibition (isolated or combined) upon the gut-liver axis, emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice. METHODS: Male C57BL/6J mice were fed a control diet (C, 10% of energy as lipids) or a high-fat diet (HFD, 50% of energy as lipids) for 12 wk, when treatments started, forming the groups: C, HF, HFA (HFD + PPAR-alpha agonist WY14643, 2.5 mg/kg body mass), HFL (HFD + DPP-4 inhibitor linagliptin, 15 mg/kg body mass), and HFC (HFD + the combination of WY14643 and linagliptin). RESULTS: The HFD was obesogenic compared to the C diet. All treatments elicited significant body mass loss, and the HFC group showed similar body mass to the C group. All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations. These metabolic benefits restored Bacteroidetes/Firmicutes ratio, resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups. At the gene level, treated groups showed higher intestinal Mucin 2, Occludin, and Zo-1 expression than the HFD group. The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals. These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol, reassuring the role of the proposed treatments on NAFLD mitigation. CONCLUSION: PPAR alpha activation and DPP-4 inhibition (isolated or combined) tackled NAFLD in diet-induced obese mice by restoration of gut-liver axis. The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through anti-inflammatory signals. These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease.
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Inhibidores de la Dipeptidil-Peptidasa IV , Endotoxemia , Enfermedad del Hígado Graso no Alcohólico , Obesidad , PPAR alfa , Animales , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Disbiosis/tratamiento farmacológico , Disbiosis/metabolismo , Endotoxemia/complicaciones , Endotoxemia/tratamiento farmacológico , Linagliptina/farmacología , Linagliptina/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , PPAR alfa/agonistas , PPAR alfa/metabolismo , FilogeniaRESUMEN
Obesity is recognized as an independent risk factor for cardiovascular diseases and is an important contributor to cardiac mortality. Açaí seed extract (ASE), rich in proanthocyanidins, has been shown to have potential anti-obesity effects. This study aimed to investigate the therapeutic effect of ASE in cardiovascular remodeling associated with obesity and compare it with that of rosuvastatin. Male C57BL/6 mice were fed a high-fat diet or a standard diet for 12 weeks. The ASE (300 mg/kg/day) and rosuvastatin (20 mg/kg/day) treatments started in the 8th week until the 12th week, totaling 4 weeks of treatment. Our data showed that treatment with ASE and rosuvastatin reduced body weight, ameliorated lipid profile, and improved cardiovascular remodeling. Treatment with ASE but not rosuvastatin reduced hyperglycemia and oxidative stress by reducing immunostaining of 8-isoprostane and increasing SOD-1 and GPx expression in HFD mice. ASE and rosuvastatin reduced NOX4 expression, increased SIRT-1 and Nrf2 expression and catalase and GPx activities, and improved vascular and cardiac remodeling in HFD mice. The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and cardiovascular remodeling but was superior in reducing oxidative damage and hyperglycemia, suggesting that ASE was a promising natural product for the treatment of cardiovascular alterations associated with obesity.
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Antioxidantes/uso terapéutico , Cardiomegalia/tratamiento farmacológico , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Remodelación Ventricular/efectos de los fármacos , Animales , Cardiomegalia/etiología , Dieta Alta en Grasa , Euterpe/química , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/complicaciones , Proantocianidinas/uso terapéutico , Semillas/químicaRESUMEN
Accumulating evidence indicates that dietary phenolic compounds can prevent obesity-related disorders. We investigated whether the consumption of polyphenol-rich jabuticaba peel and seed powder (JPSP) could ameliorate the progression of diet-induced obesity in mice. Male mice were fed a control diet or a high-fat (HF) diet for 9 weeks. After this period, mice were fed control, HF or HF diets supplemented with 5 % (HF-J5), 10 % (HF-J10) or 15 % (HF-J15) of JPSP, for 4 additional weeks. Supplementation with JPSP not only attenuated HF-induced weight gain and fat accumulation but also ameliorated the pro-inflammatory response associated with obesity, as evidenced by the absence of mast cells in the visceral depot accompanied by lower IL-6 and TNF-α at the tissue and circulating levels. JPSP-supplemented mice also exhibited smaller-sized adipocytes, reduced levels of leptin and higher levels of adiponectin, concomitant with improved glucose metabolism and insulin sensitivity. The magnitude of the observed effects was dependent on JPSP concentration with HF-J10- and HF-J15-fed mice showing metabolic profiles similar to control. This study reveals that the consumption of JPSP protects against the dysfunction of the adipose tissue and metabolic disturbances in obese mice. Thus, these findings indicate the therapeutic potential of the phenolic-rich JPSP in preventing obesity-related disorders.
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Dieta Alta en Grasa , Obesidad , Tejido Adiposo/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Ratones Obesos , Obesidad/metabolismo , Fenoles/farmacología , Fenoles/uso terapéutico , Polvos/metabolismo , Polvos/uso terapéuticoRESUMEN
This study evaluated the effect of green banana flour (GBF) consumption on obesity-related conditions in mice fed high-fat diets. GBF was prepared using stage 1 green banana pulp, which was dehydrated and milled. Mice were fed a control diet (n = 20; 10% of energy from lipids) or a high-fat diet (n = 20; 50% of energy from lipids). After 10 weeks, mice were divided into 4 groups based on feed: standard chow (SC; n = 10), standard with 15% GBF (SB; n = 10), high-fat diet (HF; n = 10) and high-fat diet with 15% GBF (HFB; n = 10) for 4 weeks. HFB exhibited lower gains in body weight (-21%; p < 0.01) and in all fat pads (p < 0.01) compared with the HF group. SC, SB, and HFB showed smaller retroperitoneal white adipose tissue diameters (p < 0.001). SB and HFB-treated mice showed lower levels of leptin, IL-6, and TNF-α compared with the SC and HF groups (p < 0.01). In the GBF-fed groups, there was a reduction in the abundance of Firmicutes (SB: -22%; HFB: -23%) and an increase in Bacteroidetes (SB: +25%; HFB: +29%) compared with their counterparts. We demonstrated that GBF consumption attenuated inflammation and improved metabolic status, adipose tissue remodeling, and the gut microbiota profile of obese mice. Novelty: Green banana flour (GBF) consumption, rich in resistant starch, regulates body weight in mice fed high-fat diets. GBF consumption improves fat pad distribution in mice fed high-fat diets. GBF improves obesity-associated systemic inflammation and regulates gut microbiota profile in mice fed high-fat diets.
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Alimentos Fortificados , Microbioma Gastrointestinal , Inflamación/fisiopatología , Musa , Obesidad/microbiología , Obesidad/fisiopatología , Adiposidad , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Interleucina-6/sangre , Leptina/sangre , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/prevención & control , Factor de Necrosis Tumoral alfa/sangre , Aumento de PesoRESUMEN
Current evidence suggests that high fructose intake results in gut dysbiosis, leading to endotoxemia and NAFLD onset. Thus, the hypothesis of the study was that an enhanced Proteobacteria proportion in the cecal microbiota could be the most prominent trigger of NAFLD through enhanced endotoxin (LPS) in adult high-fructose-fed C57BL/6 mice. Male C57BL/6 mice received a control diet (n = 10, C: 76% of energy as carbohydrates, 0% as fructose) or high-fructose diet (n = 10, HFRU: 76% of energy as carbohydrate, 50% as fructose) for 12 weeks. Outcomes included biochemical analyses, 16S rDNA PCR amplification, hepatic stereology, and RT-qPCR. The groups showed similar body masses during the whole experiment. However, the HFRU group showed greater water intake and blood pressure than the C group. The HFRU group showed a significantly lower amount of Bacteroidetes and a predominant rise in Proteobacteria, implying increased LPS. The HFRU group also showed enhanced de novo lipogenesis (Chrebp expression), while beta-oxidation was decreased (Ppar-alpha expression). These results agree with the deposition of fat droplets within hepatocytes and the enhanced hepatic triacylglycerol concentrations, as observed in the photomicrographs, where the HFRU group had a higher volume density of steatosis than the C group. Thus, we confirmed that a rise in the Proteobacteria phylum proportion was the most prominent alteration in gut-liver axis-induced hepatic steatosis in HFRU-fed C57BL/6 mice. Gut dysbiosis and fatty liver were observed even in the absence of overweight in this dietary adult mouse model.
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Dieta/efectos adversos , Disbiosis/microbiología , Fructosa/efectos adversos , Microbioma Gastrointestinal , Hígado , Enfermedad del Hígado Graso no Alcohólico/microbiología , Proteobacteria/crecimiento & desarrollo , Animales , Peso Corporal , Ciego/microbiología , Azúcares de la Dieta/efectos adversos , Modelos Animales de Enfermedad , Disbiosis/etiología , Endotoxemia/etiología , Endotoxemia/microbiología , Conducta Alimentaria , Metabolismo de los Lípidos , Lipopolisacáridos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Triglicéridos/metabolismoRESUMEN
Consumption of foods rich in phenolic compounds can be beneficial for health. This study aimed to examine whether the consumption of a phenolic-rich smoothie, based on juçara, strawberry and banana, ameliorates metabolic status and liver damage of diet-induced obese mice. Forty male C57BL/6J mice were assigned into four groups (n = 10) and fed control diet with free access to water (C) or phenolic-rich smoothie (C-S), or fed high-fat diet with free access to water (HF) or phenolic-rich smoothie (HF-S) for five weeks. HF and HF-S groups had higher body weight gains than the C group, however the HF had a greater adipose index, higher plasma levels of glucose, insulin and leptin, as well as higher plasma and hepatic steatosis than C, C-S and HF-S groups. The liver oxidative stress markers were reduced in C-S and HF-S groups and the activity of catalase and glutathione peroxidase were higher compared with their counterparts. The present study suggests that regular consumption of a phenolic-rich smoothie improves the liver antioxidant status, prevents metabolic disorders and ameliorates non-alcoholic fatty liver disease caused by high-fat diet consumption.
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Antioxidantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Fenoles/uso terapéutico , Animales , Antioxidantes/química , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/inducido químicamente , Fenoles/químicaRESUMEN
OBJECTIVES: Obesity is considered a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). The hydroalcoholic extract obtained from the açai seed (ASE), rich in proanthocyanidins, has been shown a potential body weight regulator with antioxidant properties. This study aimed to investigate the therapeutic effect of ASE in obesity-associated NAFLD and compare it with Rosuvastatin. METHODS: Male C57BL/6 mice received a high-fat diet or standard diet for 12 weeks. The treatments with ASE (300 mg/kg per day) or rosuvastatin (20 mg/kg per day) began in the eighth week until the 12th week. KEY FINDINGS: Our data show that the treatments with ASE and rosuvastatin reduced body weight and hyperglycaemia, improved lipid profile and attenuated hepatic steatosis in HFD mice. ASE and Rosuvastatin reduced HMGCoA-Reductase and SREBP-1C and increased ABGC8 and pAMPK expressions in the liver. Additionally, ASE, but not Rosuvastatin, reduced NPC1L1 and increased ABCG5 and PPAR-α expressions. ASE and rosuvastatin increased SIRT-1 expression and antioxidant defence, although only ASE was able to decrease the oxidative damage in hepatic tissue. CONCLUSIONS: The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and hepatic steatosis but was better in reducing oxidative damage and hyperglycaemia.
Asunto(s)
Euterpe , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipolipemiantes/farmacología , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Rosuvastatina Cálcica/farmacología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Dislipidemias/metabolismo , Dislipidemias/prevención & control , Euterpe/química , Hiperglucemia/metabolismo , Hiperglucemia/prevención & control , Hipolipemiantes/aislamiento & purificación , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/etiología , Obesidad/metabolismo , Obesidad/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , SemillasRESUMEN
Fructose dietary intake affects the composition of the intestinal microbiota and influences the development of hepatic steatosis. Endotoxins produced by gram-negative bacteria alter intestinal permeability and cause bacterial translocation. This study evaluated the effects of gut microbiota modulation by a purified PPAR-alpha agonist (WY14643), a DPP-4 inhibitor (linagliptin), or their association on intestinal barrier integrity, endotoxemia, and hepatic energy metabolism in high-fructose-fed C57BL/6 mice. Fifty mice were divided to receive the control diet (C group) or the high-fructose diet (HFRU) for 12 weeks. Subsequently, the HFRU group was divided to initiate the treatment with PPAR-alpha agonist (3.5 mg/kg/BM) and DPP-4 inhibitor (15 mg/kg/BM). The HFRU group had glucose intolerance, endotoxemia, and dysbiosis (with increased Proteobacteria) without changes in body mass in comparison with the C group. HFRU group showed damaged intestinal ultrastructure, which led to liver inflammation and marked hepatic steatosis in the HFRU group when compared to the C group. PPAR-alpha activation and DPP-4 inhibition countered glucose intolerance, endotoxemia, and dysbiosis, ameliorating the ultrastructure of the intestinal barrier and reducing Tlr4 expression in the liver of treated animals. These beneficial effects suppressed lipogenesis and mitigated hepatic steatosis. In conclusion, the results herein propose a role for PPAR-alpha activation, DPP-4 inhibition, and their association in attenuating hepatic steatosis by gut-liver axis modulation in high-fructose mice model. These observations suggest these treatments as potential targets to treat hepatic steatosis and avoid its progression.
Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Fructosa/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Linagliptina/farmacología , Hígado/efectos de los fármacos , PPAR alfa/fisiología , Animales , Glucemia/análisis , Dieta , Endotoxemia/prevención & control , Hígado Graso/prevención & control , Microbioma Gastrointestinal/fisiología , Intestinos/efectos de los fármacos , Intestinos/ultraestructura , Lipogénesis/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , PPAR alfa/efectos de los fármacos , Proliferadores de Peroxisomas , Pirimidinas/farmacologíaRESUMEN
NEW FINDINGS: What is the central question of this study? Does a polyphenol-rich extract from açaí have a potential role in preventing uraemic toxin-induced endothelial cell dysfunction? What is the main finding and its importance? Polyphenols from açaí prevented cell death, restored migratory capacity, protected from inflammation and contributed to the restoration of the antioxidant response in endothelial cells exposed to uraemic toxins. The protective role of açaí against toxic effects exerted by uraemic toxins presents a potential new therapeutic target in endothelial cells. ABSTRACT: In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein-bound uraemic toxins such as p-cresyl sulfate (pCS) and indoxyl sulfate (IS). Among strategies to ameliorate the harmful actions of uraemic toxins, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti-inflammatory actions of phenolic-rich açaí seed extract (ASE) in response to endothelial dysfunction induced by IS and pCS, in human umbilical vein endothelial cells (HUVECs). Cells were treated with ASE (10 µg ml-1 ) in the presence or absence of IS (61 µg ml-1 ) and pCS (40 µg ml-1 ). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes, and oxidative damage was evaluated. IS and pCS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (P < 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up-regulated pro-inflammatory cytokine expression, and ASE was able to beneficially counteract this effect. Tumour necrosis factor-α secretion was greater in uraemic toxin-treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (P < 0.05). With regard to the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (P < 0.05). From the results, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uraemic toxins (particularly by IS) in human endothelial cells.
Asunto(s)
Euterpe/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Polifenoles/farmacología , Sustancias Protectoras/farmacología , Antioxidantes , Biomarcadores/metabolismo , Muerte Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
This study aimed to investigate the effect of resistant starch from green banana (GB) on steatosis and short-chain fatty acid (SCFAs) production in high fat diet-induced obesity in mice. High-fat green banana group (HFB) exhibited lower gains in BM (body mass; -6%; P < 0.01) compared with High-fat diet group (HF). Additionally, HFB mice showed reduction in liver steatosis (-28%, P < 0.01) with reduction of 93% in hepatic triacylglycerol (P < 0.01) compared to HF-diet-fed mice. In addition, the protein abundance of AMPKp/AMPK, HMGCoA-r and FAS were downregulated in livers of HFB mice (P < 0.01), relatively to the HF-diet-fed mice. ABCG8 and ABCG5 were up-regulated in HFB group compared to HF group (P < 0.01). Furthermore, the HFB fed-mice produced the highest amount of SCFAs (p < 0.05) compared to its counterpart HFD. In conclusion, we demonstrated that resistant starch from GB improved metabolic parameters by modulating the expression of key proteins involved in liver lipid metabolism.