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1.
Nat Commun ; 11(1): 4981, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020469

RESUMEN

Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.


Asunto(s)
Adipocitos/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de la Hormona Gastrointestinal/antagonistas & inhibidores , Adipocitos/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/química , Fármacos Antiobesidad/uso terapéutico , Anticuerpos/farmacología , Anticuerpos/uso terapéutico , Peso Corporal/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Polipéptido Inhibidor Gástrico/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , Receptores de la Hormona Gastrointestinal/deficiencia , Receptores de la Hormona Gastrointestinal/metabolismo
2.
Nat Commun ; 11(1): 4982, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020474

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.


Asunto(s)
Bacterias/aislamiento & purificación , Microbioma Gastrointestinal/fisiología , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Ácidos y Sales Biliares/análisis , Ácidos y Sales Biliares/metabolismo , Biomarcadores , Heces/química , Heces/microbiología , Fibrosis , Microbioma Gastrointestinal/genética , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/metabolismo , Cirrosis Hepática/microbiología , Cirrosis Hepática/patología , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/metabolismo , Obesidad/microbiología , Obesidad/patología , Propionatos/análisis , Propionatos/metabolismo , ARN Ribosómico 16S/genética , Reproducibilidad de los Resultados
3.
Niger J Clin Pract ; 23(10): 1345-1355, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33047690

RESUMEN

Background: Several studies have demonstrated an association between obesity, periodontitis, and exercise. Aims: This study aimed to investigate the effects of regular exercise on obese women with periodontal disease, using serum, saliva, and gingival crevicular fluid (GCF) samples. A before-after study design was adopted to evaluate the effects of 12 weeks of regular exercise on obese women grouped according to periodontal status, without a control group (no exercise). The study sample comprised of 15 patients without periodontitis (NP group) and 10 patients with chronic periodontitis (CP group), from whom periodontal parameters were measured and serum, saliva, and GCF samples were collected. Body mass index (BMI), anthropometric measurements, somatotype-motoric tests, and maximal oxygen consumption (VO2max) were recorded at baseline and after exercise. Subjects and Methods: Med Calc was used for statistical analysis. Results: After exercise, a significant decrease in BMI and a significant increase in VO2max were observed in both groups. A significant decrease in probing depth and clinical attachment loss, serum leptin, GCF tumor necrosis factor-α(TNF-α) and leptin, and a significant increase in GCF resistin were observed in the CP group. A significant decrease in serum TNF-α and leptin levels and a significant increase in serum resistin and GCF TNF-α, leptin, resistin, and adiponectin levels were observed in the NP group. Significant correlations between bleeding on probing and levels of interleukin-1ß and leptin in GCF were observed in the CP group. Conclusions: This study showed that regular exercise exerts different impacts with respect to clinical and biochemical aspects of periodontal and systemic conditions in obese women.


Asunto(s)
Adipoquinas/metabolismo , Periodontitis Crónica/complicaciones , Periodontitis Crónica/metabolismo , Ejercicio Físico/fisiología , Líquido del Surco Gingival/química , Obesidad/complicaciones , Saliva/química , Adipoquinas/sangre , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Periodontitis Crónica/sangre , Femenino , Humanos , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Persona de Mediana Edad , Obesidad/sangre , Obesidad/metabolismo , Bolsa Periodontal/metabolismo , Resistina/sangre , Resistina/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
4.
Eur J Endocrinol ; 183(6): 669-676, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33112256

RESUMEN

Context: Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. Objective: To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. Design: A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m2). Methods: Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Results: Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and <0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. Conclusion: In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.


Asunto(s)
Cortisona/metabolismo , Síndrome de Cushing/etiología , Glicopéptidos/metabolismo , Hidrocortisona/metabolismo , Obesidad/metabolismo , Adulto , Arginina Vasopresina/metabolismo , Biomarcadores/metabolismo , Índice de Masa Corporal , Hormona Liberadora de Corticotropina/metabolismo , Estudios Transversales , Femenino , Glucocorticoides/metabolismo , Cabello/química , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Obesidad/complicaciones , Sistema Hipófiso-Suprarrenal/metabolismo
5.
PLoS One ; 15(10): e0236000, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33002003

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using REV-ERB agonist SR9009 in a mouse NASH model, we demonstrate the beneficial effects of REV-ERB activation that led to an overall improvement of hepatic health by suppressing hepatic fibrosis and inflammatory response.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/efectos de los fármacos , Pirrolidinas/farmacología , Tiofenos/farmacología , Animales , Modelos Animales de Enfermedad , Humanos , Inflamación/metabolismo , Lipogénesis/fisiología , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/patología , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/metabolismo
6.
Nat Commun ; 11(1): 5455, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33116140

RESUMEN

The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1ß promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.


Asunto(s)
Adipocitos Blancos/metabolismo , Adipocitos Blancos/patología , Obesidad/metabolismo , Obesidad/patología , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adipogénesis , Animales , Proteína 11 Similar a Bcl2/metabolismo , Proteínas de Ciclo Celular/deficiencia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Muerte Celular , Células Cultivadas , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/genética , Transactivadores/deficiencia , Transactivadores/genética , Transactivadores/metabolismo
7.
Nat Commun ; 11(1): 5145, 2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-33051459

RESUMEN

Based on studies in mice, leptin was expected to decrease body weight in obese individuals. However, the majority of the obese are hyperleptinemic and do not respond to leptin treatment, suggesting the presence of leptin tolerance and questioning the role of leptin as regulator of energy balance in humans. We thus performed detailed novel measurements and analyses of samples and data from our clinical trials biobank to investigate leptin effects on mechanisms of weight regulation in lean normo- and mildly hypo-leptinemic individuals without genetic disorders. We demonstrate that short-term leptin administration alters food intake during refeeding after fasting, whereas long-term leptin treatment reduces fat mass and body weight, and transiently alters circulating free fatty acids in lean mildly hypoleptinemic individuals. Leptin levels before treatment initiation and leptin dose do not predict the observed weight loss in lean individuals suggesting a saturable effect of leptin. In contrast to data from animal studies, leptin treatment does not affect energy expenditure, lipid utilization, SNS activity, heart rate, blood pressure or lean body mass.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Grasas/metabolismo , Leptina/administración & dosificación , Obesidad/tratamiento farmacológico , Delgadez/tratamiento farmacológico , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Adulto , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Energía , Femenino , Humanos , Masculino , Obesidad/metabolismo , Obesidad/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Delgadez/metabolismo , Delgadez/fisiopatología , Adulto Joven
8.
PLoS One ; 15(9): e0239274, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32946506

RESUMEN

This systematic review evaluated the association between frequency of family meals (FFM) and nutritional status (NS) and/or food consumption (FC) in adolescents. The protocol was registered with PROSPERO (CRD42017062180) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No publication date, language, or meal type restrictions were imposed. Only full-text original articles were included; qualitative studies were excluded. Studies were identified by searching 5 electronic databases (PubMed, Web of Science, Scopus, BVS Brazil, and Adolec) and gray literature (Google Scholar) and by scanning reference lists of included articles. Risk of bias was assessed using the Newcastle-Ottawa scale for cohort and cross-sectional studies. Initial search yielded 2001 results and 47 articles were included. An updated literature search added 3 articles. Of the 50 studies included, 25 studied the association between FFM and NS, 32 investigated the association between FFM and FC, being that seven studies analyzed both outcomes. Thirty-four were cross-sectional studies, 12 were longitudinal studies, and 4 studies analyzed both cross-sectional and longitudinal data. Thirty-five studies were rated as having good quality, whereas 19 were of fair quality. Sample size ranged from 140 to 102 072 participants. Most investigations evaluated the frequency of breakfast, lunch, and/or dinner/supper/evening meals over a 1-week period. Seventeen studies identified a positive relationship between high FFM and better NS, and 26 found a positive association between high FFM and better FC. In conclusion, this review showed an association between FFM and healthy dietary patterns, such as increased consumption of fruits and vegetables. Further research is needed to understand the association between FFM and NS, since some studies showed a protective role of family meals against obesity in this age group, whereas other studies identified no significant association between these variables.


Asunto(s)
Conducta Alimentaria/fisiología , Estado Nutricional/fisiología , Obesidad/epidemiología , Adolescente , Brasil/epidemiología , Niño , Manejo de Datos , Dieta , Familia , Femenino , Humanos , Almuerzo , Masculino , Comidas , Obesidad/metabolismo , Obesidad/fisiopatología
10.
PLoS Med ; 17(9): e1003307, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32931494

RESUMEN

BACKGROUND: Hypertension, together with obesity, is a leading cause of mortality and disability. Whilst metabolic surgery offers remission of several metabolic comorbidities, the effect for patients with hypertension remains controversial. The objective of the present study was to evaluate the effect of metabolic surgery on cardiovascular events and mortality on patients with morbid obesity (body mass index [BMI] ≥ 35 kg/m2) and hypertension. METHODS AND FINDINGS: We conducted a matched cohort study of 11,863 patients with morbid obesity and pharmacologically treated hypertension operated on with metabolic surgery and a matched non-operated-on control group of 26,199 subjects with hypertension (matched by age, sex, and area of residence) of varied matching ratios from 1:1 to 1:9, using data from the Scandinavian Obesity Surgery Register (SOReg), the Swedish National Patient Registers (NPR) for in-hospital and outpatient care, the Swedish Prescribed Drug Register, and Statistics Sweden. The main outcome was major adverse cardiovascular event (MACE), defined as first occurrence of acute coronary syndrome (ACS) event, cerebrovascular event, fatal cardiovascular event, or unattended sudden cardiac death. The mean age in the study group was 52.1 ± 7.46 years, with 65.8% being women (n = 7,810), and mean BMI was 41.9 ± 5.43 kg/m2. MACEs occurred in 379 operated-on patients (3.2%) and 1,125 subjects in the control group (4.5%). After adjustment for duration of hypertension, comorbidities, and education, a reduction in risk was seen in the metabolic surgery group (adjusted hazard ratio [HR] 0.73, 95% confidence intervals [CIs] 0.64-0.84, P < 0.001). The surgery group had lower risk for ACS events (adjusted HR 0.52, 95% CI 0.41-0.66, P < 0.001) and a tendency towards lower risk for cerebrovascular events (adjusted HR 0.81, 95% CI 0.63-1.01, P = 0.060) compared with controls. The main limitations with the study were the lack of information on BMI and history of smoking in the control group and the nonrandomised study design. CONCLUSION: Metabolic surgery on patients with morbid obesity and pharmacologically treated hypertension was associated with lower risk for MACEs and all-cause mortality compared with age- and sex-matched controls with hypertension from the general population.


Asunto(s)
Cirugía Bariátrica/efectos adversos , Hipertensión/metabolismo , Obesidad Mórbida/cirugía , Adulto , Cirugía Bariátrica/tendencias , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Hipertensión/cirugía , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/mortalidad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Suecia/epidemiología
11.
PLoS One ; 15(9): e0238600, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32947606

RESUMEN

Vitamin A and its metabolites are key regulators of the development of adipose tissue and associated metabolic complications. The aim of this study was to determine the effect of high fat diet and 13-cis retinoic acid (13 cRA) application on metabolic parameters, adipogenic and inflammatory indicators in female Lewis rats. Female rats of Lewis strain were fed standard laboratory diet (STD) and high fat diet (HFD, 45% of saturated fatty acids) during 30 days. The groups were divided into additional 3 groups (6 rats each): two experimental groups that received 13 cRA orally on a daily basis during 30 days (7.5 mg/kg and 15 mg/kg, respectively) and the control group that was given sunflower oil. Animals were sacrificed after 60 days. Feeding of Lewis rats with chronic HFD diet with 13 cRA supplementation increased weight gain, adiposity index, dyslipidaemia, hyperleptinaemia, insulin resistance, VLDL concentrations, oxidative stress and atherogenic indices. Administration of 13 cRA in Lewis rats fed STD did not change the weight of the animals, but it slightly increased the atherogenic parameters. 13 cRA and HFD affect metabolic parameters, glucose and lipid metabolism in Lewis rats and its administration has a completely different effect on metabolism in rats fed STD, highlighting the complex role of vitamin A supplementation in obesity. Other factors, such as genetics, age, sex, adipose tissue distribution, also must be taken into consideration.


Asunto(s)
Dieta Alta en Grasa , Glucosa/metabolismo , Isotretinoína/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Animales , Femenino , Resistencia a la Insulina , Isotretinoína/administración & dosificación , Obesidad/metabolismo , Ratas Endogámicas Lew , Aumento de Peso/efectos de los fármacos
12.
J Vis Exp ; (162)2020 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-32894273

RESUMEN

Obesity is a major worldwide public health issue that increases the risk to develop cardiovascular diseases, type-2 diabetes, and liver diseases. Obesity is characterized by an increase in adipose tissue (AT) mass due to adipocyte hyperplasia and/or hypertrophia, leading to profound remodeling of its three-dimensional structure. Indeed, the maximal capacity of AT to expand during obesity is pivotal to the development of obesity-associated pathologies. This AT expansion is an important homeostatic mechanism to enable adaptation to an excess of energy intake and to avoid deleterious lipid spillover to other metabolic organs, such as muscle and liver. Therefore, understanding the structural remodeling that leads to the failure of AT expansion is a fundamental question with high clinical applicability. In this article, we describe a simple and fast clearing method that is routinely used in our laboratory to explore the morphology of mouse and human white adipose tissue by fluorescent imaging. This optimized AT clearing method is easily performed in any standard laboratory equipped with a chemical hood, a temperature-controlled orbital shaker and a fluorescent microscope. Moreover, the chemical compounds used are readily available. Importantly, this method allows one to resolve the 3D AT structure by staining various markers to specifically visualize the adipocytes, the neuronal and vascular networks, and the innate and adaptive immune cells distribution.


Asunto(s)
Tejido Adiposo/patología , Imagenología Tridimensional , Salicilatos/farmacocinética , Adipocitos/metabolismo , Adipocitos/patología , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Humanos , Ratones , Microscopía Fluorescente , Obesidad/metabolismo , Obesidad/patología
13.
PLoS One ; 15(9): e0239547, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32970728

RESUMEN

Obesity is a common disease over the world and is tightly associated with diabetes mellitus, cardiovascular and cancer disease. Although our previous study showed that the synthetic vanadium-protein (V-P) complex had a better effect on antioxidant and antidiabetic, the relative molecular mechanisms are still entirely unknown. Hence, we investigated the effect of the synthetic V-P complex on adipocyte differentiation (adipogenesis) using human preadipocytes to clarify its molecular mechanisms of action. The primary human preadipocytes were cultured with and without V-P complex during adipocyte differentiation. The cell proliferation, lipid accumulation, and the protein expression of transcription factors and related enzymes were determined for the differentiated human preadipocytes. In this study, the 20 µg/mL of V-P complex reduced the lipid and triglyceride (TG) content by 74.47 and 57.39% (p < 0.05), respectively, and down-regulated the protein expressions of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthase (FAS). Additionally, the V-P complex significantly up-regulated the protein levels of total ß-catenin (t-ß-catenin), nuclear ß-catenin (n-ß-catenin), phosphorylated adenosine monophosphate-activated protein kinase alpha (p-AMPKα) and liver kinase B1 (p-LKB1). These showed that the inhibitory effect of V-P complex on human adipogenesis was mediated by activating Wnt/ß-catenin and LKB1/AMPK-dependent signaling pathway. Therefore, the synthetic V-P complex could be considered as a candidate for prevention and treatment of obesity.


Asunto(s)
Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Vanadio/metabolismo , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Proteína alfa Potenciadora de Unión a CCAAT/genética , Diferenciación Celular/efectos de los fármacos , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/fisiología , Ratones , Obesidad/metabolismo , PPAR gamma/metabolismo , Fosforilación , Transducción de Señal/efectos de los fármacos , Triglicéridos/metabolismo , beta Catenina/metabolismo
14.
Scand J Immunol ; 92(5): e12971, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32892401

RESUMEN

With an increase in sedentary lifestyle and dietary over nutrition, obesity has become one of the major public health problems worldwide and is a prevalent predisposing risk factor to non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western developed countries. NAFLD represents a series of diseased states ranging from non-alcoholic fatty liver (NAFL) to steatohepatitis (NASH), which can lead to fibrosis and eventually to cirrhosis and hepatocellular carcinoma. Currently, the only effective treatment to cure end-stage liver disease is liver transplantation. Macrophages have been reported to play a crucial role in the progression of NAFLD, thereby are a potential target for therapy. In this review, we discuss the current knowledge on the role of macrophages and inflammatory signalling pathways associated with obesity and chronic liver inflammation, and their contribution to NAFLD development and progression.


Asunto(s)
Hígado Graso/inmunología , Cirrosis Hepática/inmunología , Macrófagos/inmunología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Obesidad/inmunología , Receptores Depuradores/inmunología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Progresión de la Enfermedad , Hígado Graso/complicaciones , Hígado Graso/metabolismo , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Receptores Depuradores/metabolismo
15.
PLoS Genet ; 16(9): e1008916, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32877400

RESUMEN

Some imprinted genes exhibit parental origin specific expression bias rather than being transcribed exclusively from one copy. The physiological relevance of this remains poorly understood. In an analysis of brain-specific allele-biased expression, we identified that Trappc9, a cellular trafficking factor, was expressed predominantly (~70%) from the maternally inherited allele. Loss-of-function mutations in human TRAPPC9 cause a rare neurodevelopmental syndrome characterized by microcephaly and obesity. By studying Trappc9 null mice we discovered that homozygous mutant mice showed a reduction in brain size, exploratory activity and social memory, as well as a marked increase in body weight. A role for Trappc9 in energy balance was further supported by increased ad libitum food intake in a child with TRAPPC9 deficiency. Strikingly, heterozygous mice lacking the maternal allele (70% reduced expression) had pathology similar to homozygous mutants, whereas mice lacking the paternal allele (30% reduction) were phenotypically normal. Taken together, we conclude that Trappc9 deficient mice recapitulate key pathological features of TRAPPC9 mutations in humans and identify a role for Trappc9 and its imprinting in controlling brain development and metabolism.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/deficiencia , Microcefalia/genética , Obesidad/genética , Animales , Niño , Femenino , Regulación de la Expresión Génica , Frecuencia de los Genes , Impresión Genómica , Heterocigoto , Homocigoto , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Herencia Materna , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microcefalia/metabolismo , Mutación , Obesidad/metabolismo , Fenotipo
16.
Endocrinology ; 161(11)2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32880654

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has forced us to consider the physiologic role of obesity in the response to infectious disease. There are significant disparities in morbidity and mortality by sex, weight, and diabetes status. Numerous endocrine changes might drive these varied responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including hormone and immune mediators, hyperglycemia, leukocyte responses, cytokine secretion, and tissue dysfunction. Studies of patients with severe COVID-19 disease have revealed the importance of innate immune responses in driving immunopathology and tissue injury. In this review we will describe the impact of the metabolically induced inflammation (meta-inflammation) that characterizes obesity on innate immunity. We consider that obesity-driven dysregulation of innate immune responses may drive organ injury in the development of severe COVID-19 and impair viral clearance.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Inflamación/inmunología , Obesidad/inmunología , Neumonía Viral/inmunología , Betacoronavirus/fisiología , Peso Corporal/inmunología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata/inmunología , Inflamación/metabolismo , Inflamación/virología , Obesidad/metabolismo , Obesidad/virología , Pandemias , Neumonía Viral/metabolismo , Neumonía Viral/virología , Índice de Severidad de la Enfermedad
17.
Elife ; 92020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32930095

RESUMEN

Obesity and diabetes are established comorbidities for COVID-19. Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load. Acute viral infection results in ACE2 downregulation. This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system. This will be further increased in the case of pre-conditions with already compromised functioning of these systems, such as in patients with obesity and diabetes. Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function. The appearance of bacteria and/or their products in the lungs of obese and diabetic patients promotes interactions between viral and bacterial pathogens, resulting in a more severe lung injury in COVID-19.


Asunto(s)
Infecciones por Coronavirus/microbiología , Diabetes Mellitus/microbiología , Obesidad/microbiología , Neumonía Viral/microbiología , Tejido Adiposo/metabolismo , Tejido Adiposo/virología , Animales , Betacoronavirus/aislamiento & purificación , Comorbilidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/virología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/virología , Regulación hacia Abajo , Interacciones Microbiota-Huesped , Humanos , Interacciones Microbianas , Obesidad/metabolismo , Obesidad/virología , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/complicaciones , Neumonía Viral/metabolismo , Neumonía Viral/virología , Sistema Renina-Angiotensina , Carga Viral
18.
Ecotoxicol Environ Saf ; 203: 111041, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32888612

RESUMEN

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.


Asunto(s)
Dislipidemias/inducido químicamente , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Obesidad/inducido químicamente , Bifenilos Policlorados/toxicidad , Animales , Biomarcadores/análisis , Colon/microbiología , Dislipidemias/metabolismo , Dislipidemias/microbiología , Femenino , Contenido Digestivo/microbiología , Microbioma Gastrointestinal/genética , Expresión Génica/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Obesidad/microbiología , ARN Ribosómico 16S
19.
Front Immunol ; 11: 1997, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32983141

RESUMEN

Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). Therefore, there is a critical need to identify underlying metabolic factors associated with obesity that could be contributing toward increased susceptibility to SARS-CoV-2 in this vulnerable population. Here, we focus on the critical role of potent endogenous lipid metabolites known as specialized pro-resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. SPMs are generated during the transition of inflammation to resolution and have a vital role in directing damaged tissues to homeostasis; furthermore, SPMs display anti-viral activity in the context of influenza infection without being immunosuppressive. We cover evidence from rodent and human studies to show that obesity, and its co-morbidities, induce a signature of SPM deficiency across immunometabolic tissues. We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Finally, we highlight potential approaches to overcome the loss of SPMs using dietary and pharmacological interventions. Collectively, this mini-review underscores the need for mechanistic studies on how SPM deficiencies driven by obesity and environmental exposures may exacerbate the response to SARS-CoV-2.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Ácidos Docosahexaenoicos/deficiencia , Ácido Eicosapentaenoico/metabolismo , Ácido Linoleico/deficiencia , Lipoxinas/deficiencia , Obesidad/epidemiología , Obesidad/inmunología , Neumonía Viral/epidemiología , Comorbilidad , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/virología , Susceptibilidad a Enfermedades , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Humanos , Inflamación/metabolismo , Ácido Linoleico/uso terapéutico , Lipoxinas/uso terapéutico , Morbilidad , Obesidad/metabolismo , Pandemias , Neumonía Viral/dietoterapia , Neumonía Viral/virología , Factores de Riesgo
20.
Proc Natl Acad Sci U S A ; 117(37): 22962-22966, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32868418

RESUMEN

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women. A subsample of 27 also completed personality measures to examine the relationship between aromatase and personality traits related to self-regulation and inhibitory control. Results indicated that aromatase availability in the amygdala was negatively associated with body mass index (BMI) (in kilograms per square meter) and positively correlated with scores of the personality trait constraint independent of sex or age. Individual variations in the brain's capacity to synthesize estrogen may influence the risk of obesity and self-control in men and women.


Asunto(s)
Apetito/fisiología , Estrógenos/metabolismo , Obesidad/metabolismo , Adulto , Anciano , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/metabolismo , Andrógenos , Aromatasa/análisis , Inhibidores de la Aromatasa , Índice de Masa Corporal , Encéfalo/metabolismo , Estrógenos/fisiología , Femenino , Humanos , Lipogénesis , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Autocontrol
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