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INTRODUCTION: The objective of this study was to investigate the role of fenofibrate, a peroxisome proliferator-activated receptor-α agonist, in obesity-induced kidney damage (lipotoxicity) in mice with uninephrectomy. METHODS: C57BL/6 mice underwent uninephrectomy and sham surgeries and were fed normocaloric or high-fat diets. After 10 weeks, obese mice were administered 0.02% fenofibrate for 10 weeks. Kidney function and morphology were evaluated, as well as levels of inflammatory and fibrotic mediators and lipid metabolism markers. RESULTS: High-fat diet-fed mice developed characteristic obesity and hyperlipidemia, with subsequent renal lipid accumulation and damage, including mesangial expansion, interstitial fibrosis, inflammation, and proteinuria. These changes were greater in obese uninephrectomy mice than in obese sham mice. Fenofibrate treatment prevented hyperlipidemia and glomerular lesions, lowered lipid accumulation, ameliorated renal dysfunction, and attenuated inflammation and renal fibrosis. Furthermore, fenofibrate treatment downregulated renal tissue expression of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and local expression of fibroblast growth factor-21. CONCLUSION: Peroxisome proliferator-activated receptor-α activation by fenofibrate, with subsequent lipolysis, attenuated glomerular and tubulointerstitial lesions induced by renal lipotoxicity, thus protecting the kidneys of uninephrectomy mice from obesity-induced lesions. The study findings suggest a pathway in the pharmacological action of fenofibrate, providing insight into the mechanisms involved in kidney damage caused by obesity in kidney donors.
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Dieta Alta en Grasa , Fenofibrato , Hipolipemiantes , Ratones Endogámicos C57BL , Nefrectomía , Obesidad , Animales , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Ratones , Obesidad/complicaciones , Obesidad/metabolismo , Masculino , Hipolipemiantes/uso terapéutico , Hipolipemiantes/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismo , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
BACKGROUND: Lipedema is a frequently misdiagnosed condition in women, often mistaken for obesity, which significantly deteriorates both quality of life and physical health. Recognizing the necessity for holistic treatment strategies, research has increasingly supported the integration of specific dietary approaches, particularly ketogenic diets focusing on low-carbohydrate and high-fat intake. OBJECTIVES: to evaluate the impact of ketogenic diets on women with lipedema through a systematic review and meta-analysis. METHODS: A systematic review and meta-analysis were conducted by reviewing published, peer-reviewed studies addressing the implications of a low-carbohydrate, high-fat (LCHF) ketogenic diet in managing lipedema following comprehensive scrutiny of digital medical databases, such as PubMed, PubMed Central, Science Direct, and the Web of Science. This research was governed by specified parameters, including an established search string composed of search terms and an eligibility criterion (PICO) as denoted by the principal authors. Statistical analysis was carried out using RevMan 5.4.1 software with the Newcastle-Ottawa Scale utilized for quality appraisal of the included studies. RESULTS: Seven studies reporting statistical outcomes were included in the systematic review and meta-analysis following a rigorous quality appraisal and data identification process. Three hundred and twenty-nine female participants were diagnosed with lipedema and treated using a low-carbohydrate, high-fat diet. Data analysis identified the high-fat diet with a mean study duration of 15.85 weeks. Mean Differences (MDs) on changes pre- and post-intervention showed significant reductions in BMI and total body weight [4.23 (95% CI 2.49, 5.97) p < 0.00001 and 7.94 (95% CI 5.45, 10.43) p < 0.00001 for BMI and body weight, respectively]. Other anthropometric measurements, such as changes in waist/hip circumferences and waist/hip ratios, showed a significant reduction in these parameters, with an MD of 8.05 (95% CI 4.66, 11.44) p < 0.00001 and an MD of 6.67 (95% CI 3.35, 9.99) p < 0.0001 for changes in waist and hip circumferences from baseline, respectively. Lastly, changes in pain sensitivity were statistically significant post-intervention [MD 1.12 (95% CI, 0.44, 1.79) p = 0.001]. All studies scored fair on the Newcastle-Ottawa Scale. CONCLUSIONS: despite the limited studies and low number of study participants, the review observed a significant reduction in anthropometric and body composition metrics, indicating a potentially beneficial association between LCHF ketogenic diets and lipedema management.
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Dieta Alta en Grasa , Dieta Cetogénica , Lipedema , Femenino , Humanos , Dieta Alta en Grasa/métodos , Dieta Cetogénica/métodos , Lipedema/dietoterapia , Resultado del TratamientoRESUMEN
BACKGROUND/OBJECTIVES: Capsinoids are potential antioxidant agents capable of reducing oxidative damage and the resulting complications triggered by obesity. Thus, this study aimed to investigate the effects of capsinoids on adiposity and biomarkers of cardiac oxidative stress in obese rats induced by a high-fat diet. METHODS: Male Wistar rats were exposed to a high-fat diet for 27 consecutive weeks. After the characterization of obesity (week 19), some of the obese animals began to receive capsinoids (10 mg/kg/day) by orogastric gavage. Adiposity and comorbidities were assessed. In the heart, remodeling, injury, and biomarkers of oxidative stress were determined. RESULTS: The treatment did not reduce obesity-induced adiposity but was efficient in reducing cholesterol levels. Capsinoid treatment did not cause a difference in heart and LV mass, despite having reduced troponin I concentrations. Furthermore, capsinoids did not reduce the increase in the advanced oxidation of protein products and carbonylated proteins caused by obesity in cardiac tissue. In addition, obese rats treated with capsinoids presented high levels of malondialdehyde and greater antioxidant enzyme activity compared to untreated obese rats. CONCLUSIONS: In conclusion, treatment with capsinoids increases antioxidative enzyme activity and prevents obesity-induced cardiac injury without positively modulating body fat accumulation and cardiac oxidative biomarkers.
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Adiposidad , Antioxidantes , Biomarcadores , Dieta Alta en Grasa , Obesidad , Estrés Oxidativo , Ratas Wistar , Animales , Masculino , Obesidad/complicaciones , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Biomarcadores/sangre , Biomarcadores/metabolismo , Antioxidantes/farmacología , Dieta Alta en Grasa/efectos adversos , Ratas , Adiposidad/efectos de los fármacos , Miocardio/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Extractos Vegetales/farmacología , Lesiones Cardíacas/prevención & control , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/etiología , Malondialdehído/metabolismoRESUMEN
Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1ß, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS.
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Depresión , Dieta Alta en Grasa , Síndrome Metabólico , Extractos Vegetales , Salvia , Animales , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Síndrome Metabólico/etiología , Dieta Alta en Grasa/efectos adversos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Salvia/química , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/metabolismo , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos ICRRESUMEN
PURPOSE: Hibiscus sabdariffa (HS) extract has several health benefits and anti-obesogenic effects. The aim of the present study was to assess whether the medicinal properties attributable to HS would prevent or mitigate bladder changes induced by obesity in an experimental model. METHODS: Forty-eight male Wistar rats were submitted to one of four different dietary interventions (12 animals each): G1, standard diet and water (controls); G2, standard diet and HS tea; G3, a palatable high-fat diet and water; and G4, high-fat diet diet and HS tea. The animals were monitored for body weight, feed, and water and tea intake, according to the allocated group. After 16 weeks, the animals were euthanized, and the levels of creatinine, inflammatory cytokines, testosterone, cholesterol, triglycerides, and electrolytes were evaluated. In addition, histopathological analysis of the animals' bladder was performed. RESULTS: Groups receiving HS (G2 and G4) showed decreased levels of the pro-inflammatory cytokine interleukin-1α. HS tea was able to reduce low-density lipoprotein and triglyceride levels in the G2 group compared to other groups. Only in the G3 there was a significant increase in the body weight when it was compared the 12th and 16th weeks. Leptin was shown to be elevated in the groups that received a high-fat diet. There was a significant decrease in the muscle fibers thickness and in the total collagen count in G4 bladder when compared with G1 and G3. CONCLUSIONS: HS has an anti-inflammatory role, can reverse hyperlipidemia in rats, and reduced deleterious effects of obesity on these animals' bladder.
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Dieta Alta en Grasa , Hibiscus , Obesidad , Extractos Vegetales , Ratas Wistar , Vejiga Urinaria , Animales , Hibiscus/química , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Dieta Alta en Grasa/efectos adversos , Ratas , Suplementos Dietéticos , Peso Corporal/efectos de los fármacos , Triglicéridos/sangre , Modelos Animales de Enfermedad , Reproducibilidad de los Resultados , Leptina/sangreRESUMEN
Environmental factors in the early life stages can lead the descendant to adaptations in gene expression, permanently impacting several structures and organs. The amount and quality of fatty acids in the maternal diet in pregnancy and lactation were found to impact offspring metabolism. So, maternal diet and insulin resistance can affect the male and female descendants through distinct pathways and at different time points. We hypothesized that maternal high-fat diet (HFD) intake before conception and an adequate amount of different fatty acids intake during pregnancy and lactation could influence the energy homeostasis system of 21-day-old offspring. Female rats received control diet (C) or HFD (HF) for 8 weeks before pregnancy. During pregnancy and lactation C group remained with same diet (C-C), HF group were distributed into 4 groups and received C diet (HF-C), normolipidic diet based on saturated fatty acids (HF-S) or based on polyunsaturated fatty acids n-3 (HF-P) or remained in same diet (HF-HF). Maternal HFD in preconception, pregnancy, and lactation (HF-HF) led to lower glucagon-like peptide-1 levels in male (HF-HF21) compared to other groups (C-C21, HF-C21, and HF-P21) and compared to HF-HF21 females. Neuropeptide YY levels were higher in the HF-HF21, HF-C21, and HF-S21 male offspring compared to HF-P21. HF-P21 was similar to C-C21. Positive correlations were found among the energy homeostasis markers genes expressed in the offspring hypothalamus. Maternal diet changes to adequate quantities of fatty acids during pregnancy and lactation showed less impaired results but was not entirely avoided. A maternal diet based on PUFA n-3 during pregnancy and lactation seems to reverse the damage of an HFD in preconception. These results of homeostasis energy system disturbance in the offspring at weaning give us clues about changes that precede the onset of the disease in adult life - adding notes to the knowledge for future investigations of prevention and treatment of chronic diseases.
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Dieta Alta en Grasa , Metabolismo Energético , Ácidos Grasos , Intolerancia a la Glucosa , Homeostasis , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Destete , Femenino , Animales , Masculino , Embarazo , Ácidos Grasos/metabolismo , Ácidos Grasos/administración & dosificación , Dieta Alta en Grasa/efectos adversos , Ratas , Lactancia/fisiología , Ratas Wistar , Efectos Tardíos de la Exposición Prenatal , Resistencia a la InsulinaRESUMEN
AIMS: Obesity is a global public health issue, and some studies have linked it to an increased risk of prostatic diseases. This study aimed to evaluate the effects of a high-fat diet on metabolic parameters and prostate morphology in wild-type (WT) and adiponectin knockout (KO) mice. MAIN METHODS: Male WT and KO mice were fed a control diet (CD) or high-fat diet (HFD) for 6 months. Serum metabolic parameters, inflammatory cytokines in epididymal fat tissue, dorsal prostatic lobe morphometry and histopathology were analyzed. KEY FINDINGS: CD WT and CD KO mice did not exhibit altered metabolic or prostatic parameters. However, HFD WT mice showed altered glucose and insulin tolerance even without excessive weight gain. On the other hand, HFD KO mice developed obesity, with an increase in low-density lipoprotein (11.8 ± 5.1 vs. 31.4 ± 3.6 mg/dL), high-density lipoprotein (73.4 ± 7.4 vs. 103.4 ± 2.5 mg/dL), and total cholesterol levels (126.2 ± 16.1 vs. 294.6 ± 23.2 mg/dL), a decrease in insulin levels (28.7 ± 12.2 vs. 4.6 ± 2.3 µIU/mL), and glucose and insulin resistance. We also observed that HFD KO animals display an increase in inflammatory cytokines, such as IL6, IL1ß, and IL1RA. The dorsal prostate from HFD KO animals also presented significant increases in the mast cells (1.9 ± 0,7 vs. 5,3 ± 1.5 cells/field) and Ki67 index (2.91 ± 0.6 vs. 4.7 ± 0.4 %). SIGNIFICANCE: The above findings highlight the complex interactions between adiponectin, metabolism, malnutrition, and prostate health. Metabolic deregulation combined with adipose inflammation potentially induces a proliferative and inflammatory microenvironment in the prostate gland under conditions of low adiponectin production, potentially impairing prostate morphophysiology in the context of obesity and aging.
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Adiponectina , Citocinas , Dieta Alta en Grasa , Ratones Noqueados , Obesidad , Próstata , Animales , Masculino , Dieta Alta en Grasa/efectos adversos , Adiponectina/metabolismo , Adiponectina/sangre , Ratones , Citocinas/metabolismo , Próstata/patología , Próstata/metabolismo , Obesidad/metabolismo , Obesidad/patología , Obesidad/etiología , Ratones Endogámicos C57BL , Resistencia a la Insulina , Inflamación/metabolismo , Inflamación/patologíaRESUMEN
Omega-3 (ω3) fatty acids are widely investigated for their anti-inflammatory potential, however, there is little evidence regarding their action in the lung parenchyma in the context of obesity. The objective is to investigate the effects of flaxseed oil (FS), rich in α-linolenic (C18:3 - ω3), on the lungs of obese mice. Mice were fed a high-fat diet (HF) for 8 weeks to induce obesity. Subsequently, a part of these animals received HF containing FS oil for another 8 weeks. The HF consumption induced weight gain and hyperglycemia. The lung parenchyma shows a complete fatty acids profile, compared to the control group (CT). In the lung parenchyma, FS increases the ω3 content and, notwithstanding a reduction in the interleukins (IL) IL1ß and IL18 contents compared to HF. However, FS promoted increased alveolar spaces, followed by MCP1 (Monocytes Chemoattractant Protein-1) positive cell infiltration and a dramatic reduction in the anti-inflammatory cytokine, IL10. Despite reducing the pulmonary inflammatory response, the consumption of a food source of ω3 was associated with alterations in the lipid profile and histoarchitecture of the lung parenchyma, which can lead to the development of pulmonary complications. This study brings an alert against the indiscriminate use of ω3 supplements, warranting caution.
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Dieta Alta en Grasa , Aceite de Linaza , Pulmón , Obesidad , Animales , Aceite de Linaza/farmacología , Aceite de Linaza/administración & dosificación , Dieta Alta en Grasa/efectos adversos , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Obesidad/dietoterapia , Obesidad/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones , Ratones Obesos , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo , Quimiocina CCL2/metabolismo , Interleucina-10/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/administración & dosificación , Aumento de Peso/efectos de los fármacosRESUMEN
AIM: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. MATERIALS AND METHODS: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. RESULTS: Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. CONCLUSIONS: A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.
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Adiponectina , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Insulina , Leptina , Menopausia , Obesidad , Animales , Femenino , Ratones , Adiponectina/sangre , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Polipéptido Inhibidor Gástrico/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 2 Similar al Glucagón , Insulina/sangre , Leptina/sangre , Menopausia/efectos de los fármacos , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , OvariectomíaRESUMEN
Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 µg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFß, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.
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Cardiomegalia , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Fenoles , Animales , Masculino , Dieta Alta en Grasa/efectos adversos , Cardiomegalia/inducido químicamente , Cardiomegalia/patología , Ratones , Fenoles/toxicidad , Remodelación Ventricular/efectos de los fármacos , SulfonasRESUMEN
Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3ß and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.
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Tejido Adiposo , Regulación hacia Abajo , Endotelina-1 , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , Obesidad , Especies Reactivas de Oxígeno , Animales , Endotelina-1/metabolismo , Obesidad/metabolismo , Obesidad/fisiopatología , Masculino , Tejido Adiposo/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Bosentán/farmacología , Dieta Alta en Grasa , Ratones , Estrés Oxidativo , Receptor de Endotelina A/metabolismo , Receptor de Endotelina A/genética , Enzimas Convertidoras de Endotelina/metabolismo , Aorta Torácica/metabolismo , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiopatologíaRESUMEN
The present study aimed to investigate the effect of digested total protein (DTP) from chia seed on the gut microbiota and morphology of mice fed with a high-fat diet. Forty-four male C57BL/6 mice were divided into 4 groups: AIN (standard diet), HF (high-fat diet), AIN + DTP (standard diet supplemented with 400 mg of digested chia seed protein), and HF + DTP (high-fat diet supplemented with 400 mg of digested chia seed protein) during 8 weeks. Colon morphology, tight junction's gene expression, and gut microbiota composition were evaluated. The consumption of digested chia seed protein (DTP) increased the crypts width, longitudinal and circular muscular layer. Furthermore, the AIN + DTP group enhanced the expression of tight junction proteins, including occludin and claudin, while the AIN + DTP and HF + DTP groups increase the zonula occludens expression. The α-diversity analysis showed a reduction in bacterial dominance in the HF + DTP group. All the experimental groups were grouped in different cluster, showing differences in the microbiota community in the ß-diversity analyzes. The Firmicutes/Bacteroidetes ratio did not differ among the groups. The genera Olsenella and Dubosiella were increased in the AIN + DTP group, but the Oscillospiraceae_unclassified was increased in the HF + DTP group. The Alistipes was increased, while the Roseburia and Akkermansia were decreased in the AIN + DTP and HF + DTP groups. Then, the consumption of DTP from chia seed improved the gut microbiota composition and mucosal integrity, counteracting the adverse effects of high-fat diet.
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Colon , Dieta Alta en Grasa , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Proteínas de Plantas , Salvia , Semillas , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Dieta Alta en Grasa/efectos adversos , Ratones , Semillas/química , Colon/microbiología , Colon/metabolismo , Colon/efectos de los fármacos , Salvia/química , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Proteínas de Uniones Estrechas/metabolismoRESUMEN
High-intensity interval training (HIIT) has shown significant results in addressing adiposity and risk factors associated with obesity. However, there are no studies that investigate the effects of HIIT on contractility and intracellular Ca2+ handling. The purpose of this study was to explore the impact of HIIT on cardiomyocyte contractile function and intracellular Ca2+ handling in rats in which obesity was induced by a saturated high-fat diet (HFD). Male Wistar rats were initially randomized into a standard diet and a HFD group. The experimental protocol spanned 23 weeks, comprising the induction and maintenance of obesity (15 weeks) followed by HIIT treatment (8 weeks). Performance was assessed using the maximum oxygen consumption test ( V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ ). Evaluation encompassed cardiac, adipose and skeletal muscle histology, as well as contractility and intracellular Ca2+ handling. HIIT resulted in a reduction in visceral area, an increase in V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ , and an augmentation of gastrocnemius fibre diameter in obese subjects. Additionally, HIIT led to a decrease in collagen fraction, an increase in percentage shortening, and a reduction in systolic Ca2+/percentage shortening and systolic Ca2+/maximum shortening rates. HIIT induces physiological cardiac remodelling, enhancing the contractile function of cardiomyocytes and improving myofilament sensitivity to Ca2+ in the context of obesity. This approach not only enhances cardiorespiratory and physical performance but also reduces visceral area and prevents interstitial fibrosis.
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Calcio , Entrenamiento de Intervalos de Alta Intensidad , Contracción Miocárdica , Miocitos Cardíacos , Miofibrillas , Obesidad , Condicionamiento Físico Animal , Ratas Wistar , Animales , Masculino , Obesidad/fisiopatología , Obesidad/metabolismo , Obesidad/terapia , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Calcio/metabolismo , Condicionamiento Físico Animal/fisiología , Ratas , Entrenamiento de Intervalos de Alta Intensidad/métodos , Contracción Miocárdica/fisiología , Miofibrillas/metabolismo , Dieta Alta en Grasa , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Consumo de Oxígeno/fisiologíaRESUMEN
OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. METHODS: The levels of the immunoproteasome ß5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome ß5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of ß5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the ß5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.
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Dieta Alta en Grasa , Hipotálamo , Ratones Endogámicos C57BL , Neuronas , Obesidad , Complejo de la Endopetidasa Proteasomal , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Hipotálamo/metabolismo , Obesidad/metabolismo , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Masculino , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/etiología , OligopéptidosRESUMEN
Obesity is a significant health concern that is correlated with various adverse health outcomes. Diet-induced obesity (DIO) is associated with impaired cognitive function. Pharmacological treatments for obesity are limited and may have serious adverse effects. Zingiber officinale (ZO) has anti-inflammatory and antioxidant effects, in addition to metabolic effects. This study aimed to assess the effects of Zingiber officinale supplementation on cognitive function, anxiety levels, neurotrophin levels, and the inflammatory and oxidative status in the cortex following DIO in mice. Two-month-old male Swiss mice were fed DIO or standard chow for 4 months and subsequently subdivided into the following groups (n = 10 mice/group): (i) control - vehicle (CNT + vehicle); (ii) CNT supplemented with ZO (CNT + ZO); (iii) obese mice (DIO + vehicle); and (iv) obese mice supplemented with ZO (DIO + ZO) (n = 10). Zingiber officinale extract (400 mg/kg/day) was administered for 35 days via oral gavage. The DIO + vehicle group exhibited impaired recognition memory. The CNT + ZO group presented a greater number of crossings in the open field. No difference between the groups was observed in the plus maze test. DIO + vehicle increased the DCFH and carbonylation levels in the cortex. The DIO + vehicle group presented a reduction in catalase activity. The expression of inflammatory or neurotrophin markers in the cerebral cortex was not different. In conclusion, our findings indicate that supplementation with ZO reverses the cognitive impairment in DIO mice and enhances the antioxidant status of the cerebral cortex.
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Encéfalo , Disfunción Cognitiva , Dieta Alta en Grasa , Suplementos Dietéticos , Estrés Oxidativo , Zingiber officinale , Animales , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Dieta Alta en Grasa/efectos adversos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéuticoRESUMEN
This study aimed to evaluate the effects of supplementation with ethanolic and aqueous extracts from the bark of the stem of Guazuma ulmifolia in mice submitted to a high-fat diet as well as to evaluate the chemical composition of these extracts. The chemical composition and antioxidant potential was evaluated in aqueous and ethanolic extracts of the stem bark. The in vivo test consisted of evaluating the effects of the aqueous and ethanolic extracts of the stem bark on C57BL/6 mice receiving a high-fat diet. The animals were evaluated for weight gain, feed consumption, visceral adiposity, serum, and inflammatory and hormonal parameters. The results of the chemical analyses corroborate those obtained by the literature, which reported gallocatechin, epigallocatechin and epigallocatechin gallate. Compared with the ethanolic extract, the aqueous extract showed greater antioxidant capacity. Both extracts resulted in lower feed consumption in the animals, but they did not influence weight gain or visceral adiposity and resulted in varied changes in the lipid profile. In addition, they did not influence glucose tolerance, insulin sensitivity, or fasting blood glucose. Furthermore, the leptin levels increased, which may have contributed to satiety, but this was shown to have a negative impact on other inflammatory and hormonal parameters. Therefore, under the conditions of this study, the biologically active compounds present in the plant species Guazuma ulmifolia were not able to contribute to the treatment of metabolic changes related to the consumption of a high-fat diet.
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Antioxidantes , Dieta Alta en Grasa , Enfermedades Metabólicas , Ratones Endogámicos C57BL , Corteza de la Planta , Extractos Vegetales , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Dieta Alta en Grasa/efectos adversos , Corteza de la Planta/química , Ratones , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/prevención & control , Enfermedades Metabólicas/etiología , Antioxidantes/farmacología , Masculino , Apocynaceae/química , Tallos de la Planta/química , Glucemia/efectos de los fármacosRESUMEN
The consumption of a high-fat high-fructose diet partly resemble the western dietary patterns, which is closely associated with excessive body adiposity and metabolic disorders, such as obesity and type 2 diabetes. Moreover, this unhealthy regime produces unfavourable changes on the faecal microbiota, potentially interfering with microorganisms postbiotic function, such as spermidine, a natural polyamine that has been involved in the control of weight gain. The study aimed to analyse the repercussions of spermidine supplementation on somatic measurements, metabolic markers, and the faecal microbiota profile of rats fed a diet rich in fat and fructose. Indeed, Wistar males with oral administration of spermidine (20 mg/kg/day) for 6 weeks were evaluated for food and energy intake, biochemical markers, and faecal microbiota signatures. The daily use of spermidine decreased weight gain ( P < 0.01), reduced feed efficiency ( P < 0.01), and attenuated visceral fat deposition ( P < 0.01), although no effect on energy intake, hepatic weight, triglyceride and glucose index and atherogenic indexes. Similarly, the consumption of spermidine partially restored the presence of microbial species, notably Akkermansia muciniphila. Elevated concentrations of this species were linked to a decrease in triglycerides ( P = 0.04), indicating that the supplementation of spermidine might contribute to managing energy fuel homeostasis in association with an obesogenic diet.
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Dieta Alta en Grasa , Heces , Fructosa , Microbioma Gastrointestinal , Ratas Wistar , Espermidina , Animales , Espermidina/farmacología , Masculino , Dieta Alta en Grasa/efectos adversos , Fructosa/efectos adversos , Fructosa/administración & dosificación , Ratas , Microbioma Gastrointestinal/efectos de los fármacos , Heces/microbiología , Obesidad/microbiología , Aumento de Peso/efectos de los fármacos , Suplementos DietéticosRESUMEN
INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.
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Dieta Alta en Grasa , Ácidos Linoleicos Conjugados , Metabolismo de los Lípidos , Hígado , PPAR alfa , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Triglicéridos , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Masculino , Triglicéridos/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , PPAR alfa/metabolismo , PPAR alfa/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Ácidos Linoleicos Conjugados/farmacología , Lipogénesis/efectos de los fármacos , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Proteína Desacopladora 2/metabolismo , Proteína Desacopladora 2/genética , Fitosteroles/farmacología , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacos , Aumento de Peso/efectos de los fármacos , Lipoproteína Lipasa/metabolismo , Lipoproteína Lipasa/genéticaRESUMEN
The present study aimed to establish zebrafish as an experimental model for investigations into obesity and physical exercise, as well as to assess the effects of these factors on metabolism. The experiment spanned twelve weeks, comprising a feeding trial during which the last four weeks incorporated a physical exercise protocol. This protocol involved placing fifteen animals in a five-liter aquarium, where they were subjected to swimming at an approximate speed of 0.08 m/s for 30 min daily. Throughout the experiment, histological analyses of visceral, subcutaneous, and hepatic adipose tissues were conducted, along with biochemical analyses of total cholesterol and its fractions, triglycerides, glucose, lactate, and alanine aminotransferase (ALT) levels. Additionally, oxidative stress markers, such as reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and catalase activity and the formation of thiobarbituric acid-reactive substances, were investigated. The results revealed that the group fed a high-fat diet exhibited an increase in ROS production and SOD activity. In contrast, the group administered the high-fat diet and subjected to physical exercise demonstrated a notable reduction in visceral adipocyte area, hepatic steatosis levels, ALT levels, and SOD activity. These findings indicate that physical exercise has a positive effect on obesity and oxidative stress in zebrafish, providing promising evidence for future investigations in this field.
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Dieta Alta en Grasa , Estrés Oxidativo , Condicionamiento Físico Animal , Especies Reactivas de Oxígeno , Superóxido Dismutasa , Pez Cebra , Animales , Condicionamiento Físico Animal/fisiología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Hígado/metabolismo , Masculino , Tejido Adiposo/metabolismo , Triglicéridos/metabolismo , Triglicéridos/sangre , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Catalasa/metabolismo , Obesidad/metabolismo , Natación , Colesterol/metabolismo , Colesterol/sangreRESUMEN
Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (Tepidimicrobium, Acidaminobacteraceae, and Fusibacter) while promoting those linked to healthy physiology (Syntrophococcus sucrumutans, Dehalobacterium, Prevotella, and Butyricimonas). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice's continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.