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1.
Medicine (Baltimore) ; 100(5): e24061, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33592858

RESUMEN

ABSTRACT: Irisin, a novel myokine, is believed to be the crucial factor in converting white adipose tissue to beige adipose tissue. For this paper, we studied the relationship among irisin and components of metabolic syndrome (MetS), and insulin secretion and resistance in schoolchildren of Taiwan.Subjects receiving routine annual health examination at elementary school were enrolled. Demographic data, anthropometry, MetS components, irisin, and insulin secretion and resistance were collected. Subjects were divided into normal, overweight, and obese groups for evaluation of irisin in obesity. Finally, the relationship between irisin and MetS was analyzed.There were 376 children (179 boys and 197 girls), aged 10.3 ±â€Š1.5 years, were enrolled. In boys, irisin levels were not associated with body mass index percentile, body fat, blood pressure, lipid profiles, insulin secretion or resistance. After adjusting for age, the irisin level in boys was negatively related to fasting plasma glucose (FPG) (r = -0.21, P = .006). In girls, after adjusting for age, the irisin levels were positively related only to FPG (r = 1.49, P = .038). In both genders, irisin levels were similar among normal, overweight, and obese groups, and between subjects with and without MetS.The irisin levels were not associated with MetS in either boys or girls. In girls, circulating irisin levels have a nonsignificant declining trend in overweight and obese girls. However, irisin levels were negatively related to FPG in boys and positively related to FPG in girls. The contrary relationship between irisin and FPG in boys and girls needs further exploration.


Asunto(s)
Tejido Adiposo/metabolismo , Fibronectinas , Secreción de Insulina/fisiología , Insulina , Síndrome Metabólico , Sobrepeso , Antropometría/métodos , Determinación de la Presión Sanguínea/métodos , Índice de Masa Corporal , Niño , Estudios Transversales , Femenino , Fibronectinas/sangre , Fibronectinas/metabolismo , Humanos , Insulina/sangre , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Obesidad/diagnóstico , Obesidad/epidemiología , Obesidad/metabolismo , Sobrepeso/diagnóstico , Sobrepeso/epidemiología , Sobrepeso/metabolismo , Servicios de Salud Escolar/estadística & datos numéricos , Taiwán/epidemiología
3.
Nat Commun ; 12(1): 213, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431899

RESUMEN

High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.


Asunto(s)
Dieta Alta en Grasa , Exosomas/metabolismo , Resistencia a la Insulina/genética , Fosfatidilcolinas/metabolismo , Regulación hacia Arriba/genética , Tejido Adiposo/metabolismo , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Dislipidemias/complicaciones , Dislipidemias/genética , Dislipidemias/patología , Células Epiteliales/metabolismo , Hígado Graso/complicaciones , Hígado Graso/genética , Hígado Graso/patología , Heces , Regulación de la Expresión Génica , Intolerancia a la Glucosa , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Insulina/metabolismo , Interleucina-6/sangre , Intestinos/citología , Lípidos/química , Hígado/metabolismo , Hígado/patología , Activación de Macrófagos , Ratones Endogámicos C57BL , Receptores de Hidrocarburo de Aril/metabolismo , Transducción de Señal , Tetraspanina 30/metabolismo , Factor de Necrosis Tumoral alfa/sangre
4.
Nat Commun ; 12(1): 102, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397994

RESUMEN

Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.


Asunto(s)
Tejido Adiposo/metabolismo , Sistemas de Liberación de Medicamentos , Macrófagos/metabolismo , Mitocondrias/metabolismo , Obesidad/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Hígado Graso/genética , Hígado Graso/patología , Inflamación/genética , Inflamación/patología , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Obesidad/genética , Obesidad/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Pérdida de Peso/efectos de los fármacos
5.
Sensors (Basel) ; 21(2)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445436

RESUMEN

Human breath is a biomarker of body fat metabolism and can be used to diagnose various diseases, such as diabetes. As such, in this paper, a vacuum ultraviolet (VUV) spectroscopy system is proposed to measure the acetone in exhaled human breath. A strong absorption acetone peak at 195 nm is detected using a simple system consisting of a deuterium lamp source, a hollow-core fiber gas cell, and a fiber-coupled compact spectrometer corresponding to the VUV region. The hollow-core fiber functions both as a long-path and an extremely small-volume gas cell; it enables us to sensitively measure the trace components of exhaled breath. For breath analysis, we apply multiple regression analysis using the absorption spectra of oxygen, water, and acetone standard gas as explanatory variables to quantitate the concentration of acetone in breath. Based on human breath, we apply the standard addition method to obtain the measurement accuracy. The results suggest that the standard deviation is 0.074 ppm for healthy human breath with an acetone concentration of around 0.8 ppm and a precision of 0.026 ppm. We also monitor body fat burn based on breath acetone and confirm that breath acetone increases after exercise because it is a volatile byproduct of lipolysis.


Asunto(s)
Acetona/análisis , Pruebas Respiratorias/métodos , Espectrofotometría Ultravioleta/métodos , Tejido Adiposo/metabolismo , Pruebas Respiratorias/instrumentación , Diseño de Equipo , Ejercicio Físico , Voluntarios Sanos , Humanos , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Fibras Ópticas , Análisis de Regresión , Sensibilidad y Especificidad , Espectrofotometría Ultravioleta/instrumentación , Vacio , Compuestos Orgánicos Volátiles/análisis , Adulto Joven
6.
Metabolism ; 116: 154466, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33333081

RESUMEN

OBJECTIVE: Adipose tissue-derived stem cells (ASCs) might play an important role in adipose microenvironment remodelling during tissue expansion through their response to hypoxia. We examined the cytokine profiles of hypoxic visceral ASCs (hypox-visASCs) from subjects with different metabolic risk, the interactions between cytokines as well as the impact of TNFα-induced death in the behavior of surviving hypoxic subcutaneous ASCs (hypox-subASCs) both at bulk population and single-cell level. MATERIALS/METHODS: Visceral adipose tissue was processed to isolate the ASCs from 33 subjects grouped into normal weight, obese with and without metabolic syndrome. Multiplex assay was used to simultaneously measure multiple inflammatory, anti-inflammatory and angiogenic cytokines in hypox-visASCs from these patients and to elucidate cytokine profiles of hypox-subASCs upon stimulation with IL1ß or TNFα and after TNFα-induced death. qPCR and single-cell RNA-sequencing were also performed to elucidate transcriptional impact in surviving hypox-subASCs after TNFα-induced apoptosis. RESULTS: Hypox-visASCs from subjects without metabolic syndrome showed greater secretion levels of inflammatory, anti-inflammatory and angiogenic cytokines compared with those from patients with metabolic syndrome. While IL-1ß stimulation was sufficient to increase the secretion levels of these cytokines in hypox-subASCs, TNFα-induced apoptosis also increased their levels and impacted on the expression levels of extracellular matrix proteins, acetyl-CoA producing enzymes and redox-balance proteins in surviving hypox-subASCs. TNFα-induced apoptosis under different glucose concentrations caused selective impoverishment of cell clusters and differentially influenced gene expression profiles of surviving hypox-subASCs. CONCLUSIONS: Immunoregulatory and angiogenic functions of hypox-visASCs from patients with metabolic syndrome could be insufficient to promote healthy adipose tissue expansion. TNFα-induced apoptosis may impact on functionality of hypox-subASC populations, whose differential metabolic sensitivity to death could serve to manipulate individual populations selectively in order to elucidate their role in shaping adipose heterogeneity and treating metabolic disorders.


Asunto(s)
Tejido Adiposo/patología , Células Madre Adultas/metabolismo , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Síndrome Metabólico/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Tejido Adiposo/metabolismo , Células Madre Adultas/efectos de los fármacos , Células Madre Adultas/fisiología , Anciano , Apoptosis/genética , Hipoxia de la Célula/fisiología , Células Cultivadas , Femenino , Humanos , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/patología , Persona de Mediana Edad , Comunicación Paracrina/efectos de los fármacos , Comunicación Paracrina/genética , Comunicación Paracrina/fisiología , RNA-Seq , Factores de Riesgo , Análisis de la Célula Individual/métodos
7.
Metabolism ; 114: 154430, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33188786

RESUMEN

OBJECTIVE: Obesity-induced adipose tissue remodeling is closely associated with systemic insulin resistance. However, the mechanistic involvement of adipocyte-derived extracellular matrix proteins under pathophysiological conditions remains unclear. Our aim was to investigate the distinctive contributions of each chain of type VI collagens (Col6) and its cleavage protein endotrophin to adipocyte functions and insulin sensitivity. METHODS: Col6 comprises three alpha chains: Col6a1, Col6a2, and Col6a3. We generated Col6a1-, Col6a2-, and Col6a3-deficient 3T3-L1 adipocytes using the CRISPR-Cas9 system as well as a novel Col6a3-deficient (Col6a3KO) mouse model for loss-of-function studies. Adenoviral-endotrophin and adipocyte-specific doxycycline-inducible endotrophin transgenic mice were utilized for the gain-of-function analysis. RESULTS: The holo-Col6 fibrils were found to be required for mature adipocyte differentiation. Only Col6a3-deficient 3T3-L1 adipocytes showed decreased inflammation and basal adipocyte lipolysis and prevented ER-stress-induced insulin resistance. Consistently, Col6a3KO mice showed decreased adipocyte size and fat mass of epididymal adipose tissues due to a defect in adipogenic and lipolytic capacity of adipocytes. Beyond the structural role of Col6a3, overexpression of endotrophin in obese mice further augmented insulin resistance, which was tightly associated with a significant increase in lipolysis, inflammation, and cellular apoptosis in adipose tissues, whereas this showed a limited effect on adipogenesis. CONCLUSIONS: These novel findings corroborate our previous observations suggesting that adipose tissue extracellular matrix regulates adipocyte function and insulin sensitivity in pathophysiological conditions. Mechanistically, holo-Col6 fibrils and their signaling derivative endotrophin govern adipocyte function independently of their role as structural supports via MAPK signaling pathways, and the latter could be an important metabolic effector in obesity-related metabolic diseases.


Asunto(s)
Adipocitos/metabolismo , Adipogénesis/fisiología , Colágeno Tipo VI/metabolismo , Lipólisis/fisiología , Fragmentos de Péptidos/metabolismo , Células 3T3-L1 , Tejido Adiposo/metabolismo , Animales , Colágeno Tipo VI/genética , Interleucina-6/metabolismo , Ratones , Ratones Transgénicos , Fragmentos de Péptidos/genética
8.
Chemosphere ; 262: 127841, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32784060

RESUMEN

Environmental pollutants suspected of disrupting the endocrine system are considered etiologic factors in the epidemic of metabolic disorders. As regulation of energy metabolism relies on the integrated action of a large number of hormones, we hypothesized that certain chemicals could trigger changes in glucocorticoid signaling. To this end, we exposed C57Bl6/J female and male mice between 5 and 20 weeks of age to a mixture of 2,3,7,8- tetrachlorodibenzo-p-dioxin (20 pg/kg body weight/day [bw/d]), polychlorobiphenyl 153 (200 ng/kg bw/d), di-[2-ethylhexyl]-phthalate (500 µg/kg bw/d) and bisphenol A (40 µg/kg bw/d). In female mice fed a standard diet (ST), we observed a decrease in plasma levels of leptin as well as a reduced expression of corticoid receptors Nr3c1 and Nr3c2, of leptin and of various canonical genes related to the circadian clock machinery in visceral (VAT) but not subcutaneous (SAT) adipose tissue. However, Nr3c1 and Nr3c2 mRNA levels did not change in high-fat-fed females exposed to pollutants. In ST-fed males, pollutants caused the same decrease of Nr3c1 mRNA levels in VAT observed in ST-fed females but levels of Nr3c2 and other clock-related genes found to be down-regulated in female VAT were enhanced in male SAT and not affected in male VAT. The expression of corticoid receptors was not affected in the livers of both sexes in response to pollutants. In summary, exposure to a mixture of pollutants at doses lower than the no-observed adverse effect levels (NoAELs) resulted in sex-dependent glucocorticoid signaling disturbances and clock-related gene expression modifications in the adipose tissue of ST-fed mice.


Asunto(s)
Contaminantes Ambientales/toxicidad , Glucocorticoides/metabolismo , Tejido Adiposo/metabolismo , Animales , Compuestos de Bencidrilo , Peso Corporal , Contaminantes Ambientales/metabolismo , Femenino , Expresión Génica , Leptina/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fenoles , Dibenzodioxinas Policloradas/metabolismo , ARN Mensajero/metabolismo , Sensibilidad y Especificidad
9.
Chemosphere ; 262: 127891, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32799150

RESUMEN

Fluoride generally exists in the natural environment, and has been reported to induce serious environmental hazard to animals, plants, and even humans via ecological cycle. Silkworm, Bombyx mori, which showed significant growth and reproductivity reduction when exposed to fluoride, has become a model to evaluate the toxicity of fluoride. However, the detailed mechanism underlying fluoride toxicity and corresponding transport proteins remain unclear. In this study, we performed RNA-seq of the larval midgut and fat body with fluoride exposure and normal treatment. Differential analysis showed that there were 4405 differentially expressed genes in fat body and 4430 DEGs in midgut with fluoride stress. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we identified several key pathways involved in the fluoride exposure and poisoning. We focused on the oxidative phosphorylation and MAPK signal pathway. QRT-PCR confirmed that oxidative phosphorylation process was remarkably inhibited by fluoride exposure and resulted in the blocking of ATP synthesis. The MAPK signal pathway was stimulated via phosphorylation signal transduction. Moreover, by protein structure analysis combined with the DEGs, we screen 36 potential membrane proteins which might take part in transporting fluoride. Taken together, the results of our study expanded the underlying mechanisms of fluoride poisoning on silkworm larval growth and development, and implied potential fluoride transport proteins in silkworm.


Asunto(s)
Bombyx/fisiología , Fluoruros/toxicidad , Sustancias Peligrosas/toxicidad , Tejido Adiposo/metabolismo , Animales , Bombyx/metabolismo , Sistema Digestivo/metabolismo , Cuerpo Adiposo/metabolismo , Perfilación de la Expresión Génica/métodos , Inactivación Metabólica , Larva/genética , Transcriptoma/fisiología
10.
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
12.
PLoS One ; 15(10): e0239130, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33006980

RESUMEN

OBJECTIVE: Examine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes. METHODS: Fourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65-85% HRpeak) for 30d. A 120min mixed meal tolerance test was performed pre- and post-intervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO2peak), body composition (BodPod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen's d effect size (ES) was used to test group differences. RESULTS: SC tended to increase percent body fat (P = 0.06) after the intervention compared to EX+SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO2peak 2.9% compared to a 5.9% decrease with SC (P = 0.24, ES = 0.91). This increased fitness correlated to shorter operating time (r = -0.57, P = 0.03) and length of stay (r = -0.58, P = 0.03). Less omental total adiponectin (r = 0.52, P = 0.09) and leptin (r = 0.58, P = 0.05) expression correlated with shorter operating time, and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01), and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01). CONCLUSION: Adding pre-operative aerobic exercise to standard care may improve surgical outcomes through a fitness and adipose tissue derived mechanism.


Asunto(s)
Cirugía Bariátrica , Terapia por Ejercicio/métodos , Ejercicio Físico , Obesidad Mórbida/cirugía , Obesidad Mórbida/terapia , Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Adulto , Composición Corporal , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad Mórbida/metabolismo , Aptitud Física , Proyectos Piloto , Cuidados Preoperatorios/métodos , Periodo Preoperatorio , Resultado del Tratamiento
13.
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
14.
Proc Natl Acad Sci U S A ; 117(38): 23932-23941, 2020 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-32900951

RESUMEN

DICER is a key enzyme in microRNA (miRNA) biogenesis. Here we show that aerobic exercise training up-regulates DICER in adipose tissue of mice and humans. This can be mimicked by infusion of serum from exercised mice into sedentary mice and depends on AMPK-mediated signaling in both muscle and adipocytes. Adipocyte DICER is required for whole-body metabolic adaptations to aerobic exercise training, in part, by allowing controlled substrate utilization in adipose tissue, which, in turn, supports skeletal muscle function. Exercise training increases overall miRNA expression in adipose tissue, and up-regulation of miR-203-3p limits glycolysis in adipose under conditions of metabolic stress. We propose that exercise training-induced DICER-miR-203-3p up-regulation in adipocytes is a key adaptive response that coordinates signals from working muscle to promote whole-body metabolic adaptations.


Asunto(s)
Tejido Adiposo/metabolismo , ARN Helicasas DEAD-box/metabolismo , Ejercicio Físico/fisiología , Ribonucleasa III/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Adaptación Fisiológica/fisiología , Adipocitos/metabolismo , Animales , Células Cultivadas , ARN Helicasas DEAD-box/deficiencia , ARN Helicasas DEAD-box/genética , Femenino , Glucólisis , Humanos , Masculino , Ratones , Ratones Noqueados , MicroARNs/genética , MicroARNs/metabolismo , Condicionamiento Físico Animal , Ribonucleasa III/deficiencia , Ribonucleasa III/genética
15.
J Anim Sci ; 98(9)2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32877916

RESUMEN

The objective of this study was to explore the relationships between ruminal microbial populations from Angus steers that were divergent in carcass traits related to adipose accumulation. Twenty-four feedlot-finished Angus steers (age: 538 ± 21 d; body weight following lairage: 593.9 ± 43.7 kg) were slaughtered, and ruminal contents and carcass data were collected. Ruminal microbial deoxyribonucleic acid (DNA) extraction and 16S ribosomal ribonucleic acid (rRNA) gene sequencing were performed to determine microbial relative abundances, to estimate microbial diversity, and to predict microbial metabolic pathways. A variety of correlation analyses and one-way ANOVA were performed to investigate the relationships between the rumen microbiome and carcass traits. Marbling score (P = 0.001) and longissimus lipid content (P = 0.009) were positively correlated to Chao1 Richness Index, suggesting that increased intramuscular fat was associated with increased numbers of ruminal microbial species. The phyla Tenericutes and TM7 were negatively correlated (P ≤ 0.05) to marbling score and longissimus lipid content, indicating that lower abundances of these phyla may be associated with improvements in intramuscular fat content. Greater abundance of the bacterial family S24-7 was positively correlated (P = 0.002) to marbling score. Analysis by marbling classification revealed further linkages to microbial richness (P ≤ 0.063), diversity (P = 0.044), and S24-7 (P < 0.001) populations. Computational prediction of the microbial metabolic pathways revealed no differences (P ≥ 0.05) in metabolic pathway expression in rumen microbes between steers in the high- and low-marbling classes. Several phyla, families, and genera were positively correlated (P ≤ 0.05) to both rib fat thickness and yield grade. Collectively, our results suggest that microbial composition is associated to differing performance in carcass adipose traits. Overall, most of the bacterial taxa correlated to the intramuscular and subcutaneous fat depots did not overlap, suggesting the microbial population end products likely impacted adipose accumulation largely via separate adipogenic pathways of the host animal.


Asunto(s)
Bacterias/clasificación , Bovinos/microbiología , Microbioma Gastrointestinal , Carne Roja/normas , Tejido Adiposo/metabolismo , Animales , Bacterias/genética , Composición Corporal , Peso Corporal , Bovinos/fisiología , Lípidos/análisis , Masculino , Redes y Vías Metabólicas , Fenotipo , Rumen/microbiología
16.
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
17.
PLoS One ; 15(9): e0238044, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32997665

RESUMEN

INTRODUCTION: Studies report that intense physical activity influences the down-regulation of immune function in athletes as well as the interaction between adipose tissue and the immune system. AIM: This study aimed to compare the plasma soluble levels of the immune checkpoint HLA-G (sHLA-G) molecule with the fat mass and muscle mass index among 77 bodybuilders and 64 controls. RESULTS: The comparisons of the percentage of body fat (%BF) revealed that the groups of male and female bodybuilders showed a statistically significant reduction in the percentage of body fat when compared to their control group, (P <0.0001, for both comparisons). Regarding sHLA-G levels, the comparisons showed that the group of male bodybuilders had significantly higher sHLA-G levels compared to the group of female bodybuilders (P = 0.0011). CONCLUSION: Our results showed that in bodybuilders with less body fat, the systemic levels of soluble HLA-G, an immunological molecule with recognized immunosuppressive function, are significantly higher and suggest that this immune mechanism may corroborate the immunosuppressive state in athletes undergoing intense and prolonged physical training.


Asunto(s)
Tejido Adiposo/metabolismo , Biomarcadores/sangre , Ejercicio Físico , Antígenos HLA-G/sangre , Sistema Inmunológico/metabolismo , Levantamiento de Peso/estadística & datos numéricos , Tejido Adiposo/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Sistema Inmunológico/inmunología , Masculino , Adulto Joven
18.
Sheng Wu Gong Cheng Xue Bao ; 36(8): 1504-1514, 2020 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-32924349

RESUMEN

MicroRNA (miRNA) is a type of highly conserved nucleotide sequence composed of 18 to 25 nucleotides, which can specifically bind to the 3'-noncoding regions of mRNA, and then play a negative regulatory role in degrading mRNA or inhibiting translation. Long non-coding RNA (lncRNA) is a type of nucleotide sequence that exceeds 200 nucleotides in length and cannot encode proteins or can only encode protein peptides. It regulates gene expression at the levels of epigenetic, transcriptional and post-transcriptional. As an important energy storage organ, fat plays an important role in regulating the energy balance of animals, and is closely related to meat production traits such as meat production and meat quality. And the disorder of fat function can lead to hyperlipidemia, type 2 diabetes and a series of cardiovascular diseases, so the molecular regulation mechanism of animal fat deposition has attracted more attention. In recent years, more and more studies have found that miRNA and lncRNA play a crucial role in animal fat deposition. We review here the current research progresses in the role of miRNA and lncRNA in animal fat deposition, to provide theoretical guidance and new ideas for further revealing the molecular regulation mechanism of animal fat deposition.


Asunto(s)
Tejido Adiposo , MicroARNs , ARN Largo no Codificante , Tejido Adiposo/metabolismo , Animales , Diabetes Mellitus Tipo 2 , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , ARN Mensajero
19.
PLoS Genet ; 16(9): e1009018, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32925908

RESUMEN

Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin resistance already in non-diabetic individuals, we utilized the UK Biobank and METSIM cohort to perform a Mendelian randomization (MR) analyses in the non-diabetic individuals. Our results suggest that both prediabetes and systemic insulin resistance are caused by obesity (p = 1.2×10-3 and p = 3.1×10-24). As obesity reflects the amount of body fat, we next studied how adipose tissue affects insulin resistance. We performed both bulk RNA-sequencing and single nucleus RNA sequencing on frozen human subcutaneous adipose biopsies to assess adipose cell-type heterogeneity and mitochondrial (MT) gene expression in insulin resistance. We discovered that the adipose MT gene expression and body fat percent are both independently associated with insulin resistance (p≤0.05 for each) when adjusting for the decomposed adipose cell-type proportions. Next, we showed that these 3 factors, adipose MT gene expression, body fat percent, and adipose cell types, explain a substantial amount (44.39%) of variance in insulin resistance and can be used to predict it (p≤2.64×10-5 in 3 independent human cohorts). In summary, we demonstrated that obesity is a strong determinant of both prediabetes and insulin resistance, and discovered that individuals' adipose cell-type composition, adipose MT gene expression, and body fat percent predict their insulin resistance, emphasizing the critical role of adipose tissue in systemic insulin resistance.


Asunto(s)
Tejido Adiposo/metabolismo , Resistencia a la Insulina/fisiología , Obesidad/genética , Adipocitos/metabolismo , Adiposidad , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Resistencia a la Insulina/genética , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Estado Prediabético/metabolismo , Estado Prediabético/fisiopatología , Grasa Subcutánea/metabolismo
20.
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
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