RESUMEN

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.

Asunto(s)

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/patología

RESUMEN

Obesity significantly decreases life expectancy and increases the incidence of age-related dysfunctions, including ß-cell dysregulation leading to inadequate insulin secretion. Here, we show that diluted plasma from obese human donors acutely impairs ß-cell integrity and insulin secretion relative to plasma from lean subjects. Similar results were observed with diluted sera from obese rats fed ad libitum, when compared to sera from lean, calorically restricted, animals. The damaging effects of obese circulating factors on ß-cells occurs in the absence of nutrient overload, and mechanistically involves mitochondrial dysfunction, limiting glucose-supported oxidative phosphorylation and ATP production. We demonstrate that increased levels of adiponectin, as found in lean plasma, are the protective characteristic preserving ß-cell function; indeed, sera from adiponectin knockout mice limits ß-cell metabolic fluxes relative to controls. Furthermore, oxidative phosphorylation and glucose-sensitive insulin secretion, which are completely abrogated in the absence of this hormone, are restored by the presence of adiponectin alone, surprisingly even in the absence of other serological components, for both the insulin-secreting INS1 cell line and primary islets. The addition of adiponectin to cells treated with plasma from obese donors completely restored ß-cell functional integrity, indicating the lack of this hormone was causative of the dysfunction. Overall, our results demonstrate that low circulating adiponectin is a key damaging element for ß-cells, and suggest strong therapeutic potential for the modulation of the adiponectin signaling pathway in the prevention of age-related ß-cell dysfunction.

Asunto(s)

Resistencia a la Insulina , Células Secretoras de Insulina , Ratones , Humanos , Ratas , Animales , Adiponectina/metabolismo , Secreción de Insulina , Insulina/metabolismo , Obesidad/metabolismo , Células Secretoras de Insulina/metabolismo , Glucosa/metabolismo , Resistencia a la Insulina/fisiología

RESUMEN

Obesity is an abnormal or excessive accumulation of fat in the body that exacerbates metabolic and inflammatory processes, and impairs the health of afflicted individuals. ß-caryophyllene is a natural sesquiterpene that is a dietary cannabinoid with anti-inflammatory properties and potential activity against metabolic diseases. In the present study, we evaluated the effect of ß-caryophyllene on C57BL/6 mice using a diet-induced obesity model. Male mice were randomly assigned to the following groups over a 16-week period: (1) standard diet as lean control, (2) high-fat diet (HFD) as obese control, and (3) HFD + ß-caryophyllene with ß-caryophyllene at 50 mg/kg. Treatment with ß-caryophyllene improved various metabolic parameters including increased total body weight, fasting glucose levels, oral-glucose tolerance, insulin tolerance, fasting triglycerides, adipocyte hypertrophy, and liver macrovesicular steatosis. ß-caryophyllene also modulated the levels and expression of immune response factors including adiponectin, leptin, insulin, interleukin-6, tumor necrosis factor-a, and Toll-like receptor-4. Our data indicate that chronic supplementation with ß-caryophyllene can improve relevant metabolic and immunological processes in obese mice. This protocol was approved by the Institutional Committee for Care and Use of Laboratory Animals from the University of Guadalajara with protocol code CUCEI/CINV/CICUAL-01/2022.

Asunto(s)

Cannabinoides , Resistencia a la Insulina , Masculino , Ratones , Animales , Leptina , Adiponectina/metabolismo , Interleucina-6 , Cannabinoides/uso terapéutico , Glucemia/metabolismo , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , Dieta Alta en Grasa/efectos adversos , Sesquiterpenos Policíclicos , Ratones Obesos , Resistencia a la Insulina/fisiología , Triglicéridos/metabolismo , Aumento de Peso , Insulina , Antiinflamatorios/uso terapéutico , Factores de Necrosis Tumoral/uso terapéutico

RESUMEN

Aim: To investigate the effects of egg white hydrolysate (EWH) on the lipid and glycemic metabolism disruption in the white adipose tissue (WAT) dysfunction induced by mercury (Hg). Experimental: Wistar rats were treated for 60 days: control (saline, intramuscular - i.m.); hydrolysate (EWH, gavage, 1 g kg-1 day-1); mercury (HgCl2, i.m., 1st dose 4.6 µg kg-1, subsequent doses 0.07 µg kg-1 day-1) and hydrolysate-mercury (EWH-HgCl2). Hg level and histological analyses were performed in epididymal WAT (eWAT), pancreas and liver. GRP78, CHOP, PPARα, PPARγ, leptin, adiponectin, and CD11 mRNA expressions were analyzed in eWAT. The plasma lipid profile, glucose, and insulin levels were measured. Antioxidant status was also evaluated in the plasma and liver. Results: EWH intake prevented the reduced eWAT weight, adipocyte size, insulin levels, and antioxidant defenses and the increased glucose and triglyceride levels induced by Hg exposure; hepatic glutathione levels were higher in rats co-treated with EWH. The increased mRNA expression of CHOP, PPARα, and leptin induced by Hg was reduced in co-treated rats. EWH did not modify the elevated mRNA expression of GRP78, PPARγ and adiponectin in Hg-treated rats. Increased levels of Hg were found in the liver; the co-treatment did not alter this parameter. EWH prevented the morphological and metabolic disorder induced by Hg, by improving antioxidant defenses, inactivating pro-apoptotic pathways and normalizing the mRNA expression of PPARs and adipokines. Its effects enabled an increase in insulin levels and a normal balance between the fat storage and expenditure mechanisms in WAT. Conclusions: EWH may have potential benefits in the prevention and management of Hg-related metabolic disorders.

Asunto(s)

Insulinas , Mercurio , Adiponectina/genética , Adiponectina/metabolismo , Tejido Adiposo , Tejido Adiposo Blanco/metabolismo , Animales , Antioxidantes/farmacología , Clara de Huevo , Glucosa/metabolismo , Insulinas/metabolismo , Insulinas/farmacología , Leptina/metabolismo , Lípidos/farmacología , Mercurio/metabolismo , Mercurio/farmacología , PPAR alfa/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Wistar

RESUMEN

BACKGROUND: Studies have focused on the search of novel biomarkers that allow to easily identify dysfunctional adipose tissue (AT). Uric acid (UA) could be produced and reabsorbed by AT. It has been suggested that the increases of UA concentrations participates in AT dysfunction. We investigated the association of UA with morpho-functional adipose tissue markers in apparently healthy subjects. METHODS: Forty apparently healthy individuals were included. Dietary habits and anthropometrical features were evaluated. Circulating concentrations of UA, adiponectin, leptin, and plasminogen activator inhibitor-1 (PAI-1) were quantified. Periumbilical subcutaneous AT samples were obtained and adipocyte number, adipocyte area, and macrophages content were assessed. RESULTS: The present study included 40 healthy subjects (67% women) with an average age of 57 ± 9 y, BMI of 26 ± 4 (kg/m2). UA showed a significant association with the number and mean area of adipocytes, macrophages number, adiponectin, and PAI-1. Although UA was independently associated with the number and mean area of adipocytes, macrophages number, adiponectin into the adjusted multivariable model. CONCLUSION: UA concentrations are associated with morpho-functional adipose tissue markers. Our results underscore the importance of UA as one earlier instigator of adipose tissue dysfunction in subjects without metabolic abnormalities.

Asunto(s)

Inhibidor 1 de Activador Plasminogénico , Ácido Úrico , Adipoquinas/metabolismo , Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Anciano , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Inhibidor 1 de Activador Plasminogénico/metabolismo , Ácido Úrico/metabolismo

RESUMEN

Polycystic ovary syndrome (PCOS) is an endocrine/metabolic disorder associated with insulin resistance (IR) and obesity. Endometria from women with PCOS present failures in insulin action, glucose uptake and signaling of insulin-sensitizing molecules, such as adiponectin, with consequences for reproduction. Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood. This study addresses the MTF effect, as well as adiponectin agonist action, on levels of molecules associated with insulin and adiponectin signaling pathways in endometrial tissue and cells, as assessed by immunohistochemistry and immunocytochemistry, respectively. Endometrial tissues were obtained from women and divided into five groups: Normal Weight (control); Obesity + IR; Obesity + IR + PCOS; Obesity + IR + MTF; Obesity + IR + PCOS + MTF. Endometrial cells stimulated with TNFα (as obesity-marker) were also used to partially emulate an obesity environment. The results showed low levels of insulin/adiponectin signaling in the endometria from women with obesity, IR and PCOS compared with the control group. MTF re-established these levels, independently of PCOS. TNFα-associated molecules were elevated in pathologic endometria, whereas MTF diminished these levels. The low levels of insulin/adiponectin molecules in endometrial cells treated with TNFα were reverted by MTF, similar to what was observed in the case of the adiponectin agonist. Therefore, independently of PCOS, MTF can re-establish levels of molecules involved in insulin/adiponectin signaling in endometrial cells, suggesting an improvement in insulin action and reproductive failures observed in endometria from women with obesity/PCOS.

Asunto(s)

Resistencia a la Insulina , Metformina , Síndrome del Ovario Poliquístico , Adiponectina/metabolismo , Endometrio/metabolismo , Femenino , Humanos , Insulina/metabolismo , Metformina/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Intermittent fasting (IF) and high-intensity interval training (HIIT) are procedures that might mitigate the effects of nonalcoholic fatty liver disease. Two groups of 3-month-old C57BL/6 male mice were fed for 16 weeks with a control (C) or high-fat (HF) diet. In the last 4 weeks of the study, IF, HIIT, and IF/HIIT were implemented. Obese HF animals showed liver fat accumulation with macro-, and micro-vesicular steatosis and inflammatory infiltrate. IF and HIIT successfully reduced liver steatosis in the HF-derived groups. IF, HIIT, and IF/HIIT were beneficial in improving glucose metabolism in both C-derived and HF-derived groups. High levels observed in plasmatic and liver levels of total cholesterol and triacylglycerol in the HF group compared to the C group were mitigated by IF, HIIT, and IF/HIIT. IF decreased adiponectin and increased leptin and insulin in the HF group. HIIT improved adiponectin and leptin. IF chances liver gene expressions: increased interleukin-6 (IL-6) in the C IF group, reduced IL-6, and PAI-1 in the HF group. IF/HIIT reduced IL-6, MCP-1, and PAI-1. IF and HIIT enhanced hepatic beta-oxidation. However, lipogenesis was reduced by IF and HIIT in the HF-derived groups. In conclusion, IF and HIIT benefit weight loss, hormones, glucose tolerance/insulin resistance, liver steatosis/inflammation, fatty acid oxidation, and lipogenesis. Furthermore, the IF groups showed beneficial effects more often and intensely than HIIT ones. The IF/HIIT combination was slightly more efficient than IF, indicating that IF is the primary intervening factor benefiting the obese mouse liver.

Asunto(s)

Entrenamiento de Intervalos de Alta Intensidad , Enfermedad del Hígado Graso no Alcohólico , Adiponectina/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Ayuno , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Interleucina-6/metabolismo , Leptina/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/terapia , Inhibidor 1 de Activador Plasminogénico/metabolismo

RESUMEN

We postulated that Green tea (GT) improvements in non-alcoholic fatty liver disease (NAFLD) are dependent on adiponectin action in the liver. Male wild-type and adiponectin knockout (adipoKO) mice were induced to obesity for 8 weeks with a high-fat diet and then treated with GT for the last 12 weeks of the experimental protocol. Glucose and insulin tolerance tests, indirect calorimetry, histologic analysis of liver sections, and quantification of mRNA of hepatic genes related to glucose or fatty acid metabolism were performed. In vitro, we assessed the mechanism by which GT catechins act to improve hepatic steatosis by measuring lipid accumulation, and transcript levels of lipogenic genes in HepG2 cells treated with GT in the presence of a PPAR antagonist. Additionally, we performed a PPAR transactivation assay in 293T cells to test if catechins could activate PPARs. Different from wild-type mice, adipoKO animals treated with GT and fed a HFD gain body weight and fat mass, that were associated with a decrease in energy expenditure, were insulin resistant, and had no improvements in hepatic steatosis. Increased lipid levels were associated with no modulation of PPARα levels in the liver of adipoKO mice treated with GT. In vitro, we demonstrated GT catechins act to reduce hepatic steatosis in a PPARα-dependent manner, and especially epigallocatechin and epicatechin can indirectly activate PPARα, although it seems they are not direct ligands. By providing the mechanisms by which GT catechins act in the liver to improve steatosis, our data contribute to the discovery of novel therapeutic agents in the management of NAFLD.

Asunto(s)

Enfermedad del Hígado Graso no Alcohólico , PPAR alfa , Adiponectina/metabolismo , Animales , Antioxidantes/metabolismo , Dieta Alta en Grasa/efectos adversos , Glucosa/metabolismo , Insulina/metabolismo , Metabolismo de los Lípidos , Lípidos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Té/química

RESUMEN

White adipose tissue hyperplasia has been shown to be crucial for handling excess energy in healthy ways. Though adipogenesis mechanisms have been underscored in vitro, we lack information on how tissue and systemic factors influence the differentiation of new adipocytes. While this could be studied in zebrafish, adipocyte identification currently relies on neutral lipid labeling, thus precluding access to cells in early stages of differentiation. Here we report the generation and analysis of a zebrafish line with the transgene fabp4a(-2.7):EGFPcaax. In vivo confocal microscopy of the pancreatic and abdominal visceral depots of transgenic larvae, revealed the presence of labeled mature adipocytes as well as immature cells in earlier stages of differentiation. Through co-labeling for blood vessels, we observed a close interaction of differentiating adipocytes with endothelial cells through cell protrusions. Finally, we implemented hyperspectral imaging and spectral phasor analysis in Nile Red-labeled transgenic larvae and revealed the lipid metabolic transition towards neutral lipid accumulation of differentiating adipocytes. Altogether our work presents the characterization of a novel adipocyte-specific label in zebrafish and uncovers previously unknown aspects of in vivo adipogenesis. This article has an associated First Person interview with the first author of the paper.

Asunto(s)

Adipocitos/fisiología , Adipogénesis/genética , Tejido Adiposo Blanco/citología , Diferenciación Celular/genética , Pez Cebra/embriología , Adiponectina/metabolismo , Animales , Animales Modificados Genéticamente , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Línea Celular , Factor D del Complemento/metabolismo , Células Endoteliales/fisiología , Proteínas de Unión a Ácidos Grasos/metabolismo

RESUMEN

Pomegranate juice (Punica granatum) has been used since ancient times in traditional medicine (Unani Medicine, Ayurveda); its main compounds are anthocyanins and ellagic acid, which have anti-inflammatory, antioxidant, hepatoprotective, and cardiovascular health effects. The objective was to evaluate the effect of pomegranate juice on inflammation, blood pressure, and vascular and physiological markers associated with obesity induced by a high-fat diet in a murine model. The results show that pomegranate juice reduces the concentration of low-density lipoprotein cholesterol (cLDL) 39% and increases the concentration of high-density lipoprotein cholesterol (cHDL) by 27%, leading to a 12%-18% decrease in the risk of cardiovascular diseases (CVD). In addition to reducing blood pressure by 24%, it also had an antiatherogenic effect by decreasing sE-selectin levels by 42%. On the other hand, the juice significantly increased adiponectin levels in adipose tissue, decreased levels of inflammation markers (tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-17A (IL-17A), interleukin-6 (IL-6), interleukin-1ß (IL-1ß)), and inhibited the monocyte chemoattractant protein-1 (MCP-1). Pomegranate juice requires clinical studies to prove its immunoregulatory and therapeutic effects on cardiovascular and atherogenic risks.

Asunto(s)

Tejido Adiposo/metabolismo , Enfermedades Cardiovasculares/prevención & control , Jugos de Frutas y Vegetales , Factores de Riesgo de Enfermedad Cardiaca , Inflamación , Obesidad/fisiopatología , Granada (Fruta) , Adiponectina/metabolismo , Tejido Adiposo/inmunología , Animales , Biomarcadores/análisis , Presión Sanguínea , Enfermedades Cardiovasculares/etiología , Quimiocina CCL2/antagonistas & inhibidores , Citocinas/metabolismo , Dieta Alta en Grasa , Ingestión de Energía , Jugos de Frutas y Vegetales/análisis , Lípidos/sangre , Masculino , Obesidad/complicaciones , Ratas , Ratas Wistar

RESUMEN

Many approaches have been used in the effective management of type 2 diabetes mellitus. A recent paradigm shift has focused on the role of adipose tissues in the development and treatment of the disease. Brown adipose tissues (BAT) and white adipose tissues (WAT) are the two main types of adipose tissues with beige subsets more recently identified. They play key roles in communication and insulin sensitivity. However, WAT has been shown to contribute significantly to endocrine function. WAT produces hormones and cytokines, collectively called adipocytokines, such as leptin and adiponectin. These adipocytokines have been proven to vary in conditions, such as metabolic dysfunction, type 2 diabetes, or inflammation. The regulation of fat storage, energy metabolism, satiety, and insulin release are all features of adipose tissues. As such, they are indicators that may provide insights on the development of metabolic dysfunction or type 2 diabetes and can be considered routes for therapeutic considerations. The essential roles of adipocytokines vis-a-vis satiety, appetite, regulation of fat storage and energy, glucose tolerance, and insulin release, solidifies adipose tissue role in the development and pathogenesis of diabetes mellitus and the complications associated with the disease.

Asunto(s)

Tejido Adiposo/metabolismo , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Adipoquinas/metabolismo , Adiponectina/metabolismo , Tejido Adiposo Beige/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Metabolismo Energético/fisiología , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Leptina/metabolismo , Obesidad/metabolismo

RESUMEN

The nutrient sensors peroxisome proliferator-activated receptor γ (PPARγ) and mechanistic target of rapamycin complex 1 (mTORC1) closely interact in the regulation of adipocyte lipid storage. The precise mechanisms underlying this interaction and whether this extends to other metabolic processes and the endocrine function of adipocytes are still unknown. We investigated herein the involvement of mTORC1 as a mediator of the actions of the PPARγ ligand rosiglitazone in subcutaneous inguinal white adipose tissue (iWAT) mass, endocrine function, lipidome, transcriptome and branched-chain amino acid (BCAA) metabolism. Mice bearing regulatory associated protein of mTOR (Raptor) deletion and therefore mTORC1 deficiency exclusively in adipocytes and littermate controls were fed a high-fat diet supplemented or not with the PPARγ agonist rosiglitazone (30 mg/kg/day) for 8 weeks and evaluated for iWAT mass, lipidome, transcriptome (Rnaseq), respiration and BCAA metabolism. Adipocyte mTORC1 deficiency not only impaired iWAT adiponectin transcription, synthesis and secretion, PEPCK mRNA levels, triacylglycerol synthesis and BCAA oxidation and mRNA levels of related proteins but also completely blocked the upregulation in these processes induced by pharmacological PPARγ activation with rosiglitazone. Mechanistically, adipocyte mTORC1 deficiency impairs PPARγ transcriptional activity by reducing PPARγ protein content, as well as by downregulating C/EBPα, a co-partner and facilitator of PPARγ. In conclusion, mTORC1 and PPARγ are essential partners involved in the regulation of subcutaneous adipose tissue adiponectin production and secretion and BCAA oxidative metabolism.

Asunto(s)

Adiponectina/metabolismo , Aminoácidos de Cadena Ramificada/metabolismo , Glicerol/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , PPAR gamma/metabolismo , Grasa Subcutánea/metabolismo , Regulación hacia Arriba , Animales , Ratones , Oxidación-Reducción

RESUMEN

Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.

Asunto(s)

Regulación de la Expresión Génica , Síndrome Metabólico/complicaciones , Síndrome Metabólico/metabolismo , Neoplasias/complicaciones , Neoplasias/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Animales , Progresión de la Enfermedad , Humanos , Hiperglucemia/metabolismo , Hipertensión/metabolismo , Inflamación , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leptina/metabolismo , Ligandos , Ratones , Obesidad/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Ratas , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Wnt/metabolismo

RESUMEN

AIM: To analyse the expression of adiponectin (ADIPOQ), and its receptors ADIPOR1 and ADIPOR2, in breast cancer tissue of postmenopausal women with different body mass indexes (BMIs). SUBJECTS AND METHODS: One hundred and fifty postmenopausal Mexican-Mestizo women with breast cancer were included. BMI was determined in each case. To carry out qualitative and semiquantitative assessments of protein expression by immunohistochemistry, the H-Score method was used, through ImageJ's IHC Profiler software. Statistical power of the study was >80% with a p<0.05. RESULTS: Fifty women had a normal BMI, 50 presented overweight and 50 had obesity. The expression of ADIPOQ in breast cancer tissue of postmenopausal woman with normal BMI was higher in comparison to women with overweight or with obesity (p=0.002 and p<0.001, respectively). Furthermore, the expression of ADIPOR1 in breast cancer tissue of postmenopausal women with normal BMI was significantly lower when compared with women with overweight or with obesity (p=0.005 and p<0.001, respectively). Meanwhile, the expression of ADIPOR2 in breast cancer tissue, in the cytoplasm, was similar in all groups studied. CONCLUSIONS: We found that women with overweight or obesity had a lower expression of ADIPOQ and a higher ADIPOR1 expression in breast cancer tissue, when compared with women with a normal BMI.

Asunto(s)

Adiponectina/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Obesidad/complicaciones , Receptores de Adiponectina/metabolismo , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/complicaciones , Femenino , Humanos , México , Persona de Mediana Edad , Posmenopausia

RESUMEN

Adiponectin, among other diverse adipokines, is produced in greater quantity and has an effect on the adipose tissue and other tissues in the body. Adiponectin plays three main roles: regulatory metabolic and sensitizing function of insulin in the liver and muscles; it acts as an anti-inflammatory cytokine and in vascular protection, besides important cardiac protection in the presence of ischemia-reperfusion syndrome. Since many situations resulting from traumatic accidents or pathologies are due to cell damage caused by ischemia-reperfusion syndrome, it is relevant to study new therapeutic alternatives that will contribute to reducing these lesions. The objective of this study is to carry out a literature review on the role of adiponectin in ischemia-reperfusion syndrome.

Asunto(s)

Adiponectina/metabolismo , Isquemia/metabolismo , Daño por Reperfusión , Tejido Adiposo , Citocinas , Humanos , Síndrome Metabólico

RESUMEN

In 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have reported high circulating adiponectin levels positively associated with cardiovascular mortality and all-cause mortality. These results are biologically intriguing and counterintuitive, and came to be termed "the adiponectin paradox". Adiponectin paradox is frequently associated with adiponectin resistance, a concept related with the downregulation of adiponectin receptors in insulin-resistant states. We review this contradiction between the apparent role of adiponectin as a health promoter and the recent evidence from Mendelian randomization studies indicating that circulating adiponectin levels are an unexpected predictor of increased morbidity and mortality rates in several clinical conditions. We also critically review the therapeutic perspective of synthetic peptide adiponectin receptors agonist that has been postulated as a promising alternative for the treatment of metabolic syndrome and type 2 diabetes mellitus.

Asunto(s)

Adiponectina/metabolismo , Enfermedades Cardiovasculares/patología , Síndrome Metabólico/patología , Receptores de Adiponectina/metabolismo , Animales , Enfermedades Cardiovasculares/metabolismo , Humanos , Síndrome Metabólico/metabolismo

RESUMEN

Our goal was to establish the requirement of ß3 adrenoceptor (ß3Adr) for green tea (GT) effects on the energy metabolism of obese mice. This study was carried out in wild-type (WT) and ß3Adr knockout (KO) male mice fed with a standard diet or a high-fat diet (HFD/16 weeks) treated or not with GT (0.5 g/kg of body weight (BW)/12 weeks). GT-treatment attenuated final BW, BW gain, and adiposity index increased by HFD, improving insulin resistance (IR) and FGF21 level, without changing the food intake of WT mice. GT-treatment of ß3AdrKO mice attenuated only IR, denoting GT-effects independent of ß3Adr. We observed increased lipolysis accompanied by decreased adipocyte size in white adipose tissue (WAT) as well as browning of the subcutaneous WAT induced by GT in a way dependent on ß3Adr. In brown adipose tissue (BAT) mRNA levels of lipolytic/oxidative genes, including ß3Adr/Ucp1 and energy expenditure (EE) was increased by GT dependent on ß3Adr. GT-treatment increased adiponectin independent of ß3Adr. Also, independent of ß3Adr pathway GT promoted an increase in ß2Adr/Ucp1 mRNA levels and EE in BAT whereas; in the liver, GT has a dual role in increasing lipid synthesis and oxidation. These data lead us to suggest that GT uses ß3Adr pathway activation to achieve some of its beneficial health effects.

Asunto(s)

Fármacos Antiobesidad/farmacología , Camellia sinensis , Metabolismo Energético/efectos de los fármacos , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Receptores Adrenérgicos beta 3/deficiencia , Adiponectina/genética , Adiponectina/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/patología , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Adiposidad/efectos de los fármacos , Animales , Fármacos Antiobesidad/aislamiento & purificación , Camellia sinensis/química , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Lipólisis/efectos de los fármacos , Masculino , Ratones Noqueados , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Extractos Vegetales/aislamiento & purificación , Receptores Adrenérgicos beta 3/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Aumento de Peso/efectos de los fármacos

RESUMEN

Background: Leptin and adiponectin interact with each other in the modulation of obesity and insulin resistance (IR) and it is also important to consider the role of cardiorespiratory and muscular fitness in these relationships.Aim: To analyse the relationship between IR with adipocytokines in children, and to test the mediation effect of %BF (percentage of body fat) in the association of IR with leptin, adiponectin, and L/A ratio.Subjects and methods: This cross-sectional study comprised a sample of 150 schoolchildren, aged 6-11 years, from school in Porto Alegre, Brazil. The following variables were evaluated: cardiorespiratory fitness (CRF), muscular fitness (MF), percentage of body fat (%BF), and biochemical variables (leptin, adiponectin, glucose, and insulin).Results: IR was associated with leptin and L/A ratio, after adjustments for age, sex, sexual maturation, and CRF. When adjusted for age, sex, sexual maturation, and MF, an association was found between IR with leptin and L/A ratio. Moreover, %BF was a mediator in the association between IR and leptin, as well as IR and L/A ratio, explaining 54% and 57% of these associations, respectively.Conclusion: Leptin and L/A ratio are positively associated with IR after adjustments. Also, %BF is a mediator in the associations between IR and leptin and L/A ratio.

Asunto(s)

Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Adiposidad , Resistencia a la Insulina , Leptina/metabolismo , Brasil , Niño , Estudios Transversales , Humanos

RESUMEN

Clinical and experimental evidences indicate that epigenetic modifications induced by the prenatal environment are related to metabolic and reproductive derangements in polycystic ovary syndrome (PCOS). Alterations in the leptin and adiponectin systems, androgen signalling and antimüllerian hormone (AMH) levels have been observed in PCOS women and in their offspring. Using a targeted Next-Generation Sequencing (NGS), we studied DNA methylation in promoter regions of the leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), adiponectin receptor 1 and 2 (ADIPOR1 and ADIPOR2), AMH and androgen receptor (AR) genes in 24 sons and daughters of women with PCOS (12 treated with metformin during pregnancy) and 24 children born to non-PCOS women during early infancy (2-3 months of age). Genomic DNA was extracted from whole blood, bisulphite converted and sequenced by NGS. Girls showed differences between groups in 1 CpG site of LEPR, 2 of LEP, 1 of ADIPOR2 and 2 of AR. Boys showed differences in 5 CpG sites of LEP, 3 of AMH and 9 of AR. Maternal metformin treatment prevented some of these changes in LEP, ADIPOR2 and partially in AR in girls, and in LEP and AMH in boys. Maternal BMI at early pregnancy was inversely correlated with the methylation levels of the ChrX-67544981 site in the whole group of girls (r = -0.530, p = 0.008) and with the global Z-score in all boys (r = -0.539, p = 0.007). These data indicate that the intrauterine PCOS environment predisposes the offspring to acquire certain sex-dependent DNA methylation patterns in the promoter regions of metabolic and reproductive genes.

Asunto(s)

Metilación de ADN , Epigénesis Genética , Síndrome del Ovario Poliquístico/genética , Efectos Tardíos de la Exposición Prenatal/genética , Adiponectina/genética , Adiponectina/metabolismo , Adulto , Femenino , Humanos , Lactante , Leptina/genética , Leptina/metabolismo , Masculino , Embarazo , Regiones Promotoras Genéticas , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Leptina/genética , Receptores de Leptina/metabolismo

RESUMEN

Adiponectin is downregulated in obesity negatively impacting the thermogenesis and impairing white fat browning. Despite the notable effects of green tea (GT) extract in the enhancement of thermogenesis, if its effects are being mediated by adiponectin has been scarcely explored. For this purpose, we investigated the role of adiponectin in the thermogenic actions of GT extract by using an adiponectin-knockout mice model. Male wild-type (WT) and knockout (AdipoKO) C57Bl/6 mice (3 months) were divided into 6 groups: mice fed a standard diet+gavage with water (SD WT, and SD AdipoKO), high-fat diet (HFD)+gavage with water (HFD WT, and HFD AdipoKO), and HFD + gavage with 500 mg/kg of body weight (BW) of GT extract (HFD + GT WT, and HFD + GT AdipoKO). After 20 weeks of experimentation, mice were euthanized and adipose tissue was properly removed. Our findings indicate that treatment with GT extract reversed complications of obesity in WT mice by decreasing final BW gain, adiposity index, adipocyte size and insulin resistance (IR). However, the action of the GT extract was not effective in reversing those markers in the AdipoKO mice, although GT acts independently in the reversal of IR. GT-treatment induced enhancement in energy expenditure (EE), BAT thermogenesis, and promoted browning phenotype in the subcutaneous WAT (scWAT) of WT mice. On the other hand, the thermogenic program was markedly impaired in BAT and scWAT of AdipoKO mice. Our outcomes unveiled adiponectin as a key direct signal for GT extract inducing adaptive thermogenesis and browning in scWAT.

Asunto(s)

Adiponectina/metabolismo , Extractos Vegetales/farmacología , Polifenoles/química , Té/química , Termogénesis , Adipocitos/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Adiposidad , Animales , Dieta Alta en Grasa , Metabolismo Energético/efectos de los fármacos , Glucosa/metabolismo , Homeostasis , Resistencia a la Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/metabolismo , Transducción de Señal/efectos de los fármacos