Study of immune population infiltrated in white adipose tissue: Novel target genes in obesity and metabolic diseases

[eng] Obesity is a chronic condition, with a multifactorial etiology whose incidence has tripled in the last four decades. This condition is associated with a low-grade inflammation caused by an activation of the proinflammatory response of immune cells WAT-infiltrating, which can lead to different comorbidities, directly affecting life expectancy. WAT is the main organ responsible for energy storage, in the form of lipids. But also act as an endocrine organ being able to respond to metabolic changes. Therefore, it promotes changes in whole metabolism leading to the development of IR and an increased cardiometabolic risk. Additionally, the WAT is distributed into two depots: SAT and VAT, each with its own biochemical features and metabolic functions. It has been described that SAT has a protective role it is inversely associated with glucose intolerance, IR, and risk of T2D diagnosis. At the same time VAT is linked with a worsening of metabolic status. WAT is an organ composed by heterogeneous population of cells including pre-adipocytes, fibroblasts, endothelial cells, stem cells and immune cells which changes according to metabolic status. The immune cells regulate WAT function, which is disrupted in obesity, promoting inflammatory signalling which lead to inflammatory, hypoxic, and fibrotic events in WAT. Because the WAT-infiltrated macrophages are the most abundant immune population in WAT, its contribute to a highest proportion to the disruption of homeostasis in obese WAT. However, little is known about which genes or pathways are altered in whole VAT compared to SAT, which promote the development of metabolic diseases. For thus, the objective of this work was determining gene targets that contribute to a worse metabolic prognosis to find its possible role in the development of obesity, related with each depot and infiltrating macrophages. We show for the first time that the phenotype of macrophages infiltrating in WAT have a different gene expression profile according to the depot. Our work proposes novel targets involved in obesity and related metabolic diseases.[spa] La obesidad es una condición crónica cuya incidencia se ha triplicado en las últimas cuatro décadas. Esta condición está asociada a una activación de la respuesta proinflamatoria de las células inmunes infiltradas en el WAT, lo que puede conducir a diferentes comorbilidades, afectando directamente la esperanza de vida. El WAT es órgano principal de almacenamiento de lípidos, pero también actúa como un órgano endocrino pudiendo responder a cambios metabólicos. Por lo tanto, cambios en este tejido puede conducir el desarrollo de comorbilidades asociadas a obesidad. El WAT se distribuye en dos depósitos: SAT y VAT, cada uno con sus propias funciones metabólicas. Se ha descrito que la SAT tiene un papel protector y se asocia inversamente con el desarrollo de IR y T2D. Al mismo tiempo, el VAT está relacionado con un empeoramiento del estado metabólico. Este tejido, está compuesto por una población heterogénea de células que incluyen preadipocitos, fibroblastos, células endoteliales, células madre y células inmunitarias que cambian según el estado metabólico. Las células inmunitarias regulan la función del WAT, que, en condición de obesidad, promueven la activación de la una señalización inflamatoria, hipóxica y fibrótica en este tejido. Debido a que los ATMs son la población inmune más abundante contribuyen en una proporción más alta a la alteración de la homeostasis en WAT en sujetos obesos. Actualmente existe poca información respecto a vías de señalización alteradas en VAT en respecto a SAT asociadas al desarrollo de enfermedades metabólicas. Por ello, el objetivo de este trabajo fue determinar dianas genéticas que contribuyan a un peor pronóstico metabólico para encontrar su posible papel en el desarrollo de la obesidad. Nuestro trabajo muestra por primera vez que el fenotipo de ATMs tienen un perfil de expresión génica diferente según el depósito estudiado. Nuestro trabajo propone nuevas dianas implicadas en la obesidad y enfermedades metabólicas relacionadas

Study of immune population infiltrated in white adipose tissue: Novel target genes in obesity and metabolic diseases

Programa de Doctorat en Alimentació i Nutrició[eng] Obesity is a chronic condition, with a multifactorial etiology whose incidence has tripled in the last four decades. This condition is associated with a low-grade inflammation caused by an activation of the proinflammatory response of immune cells WAT-infiltrating, which can lead to different comorbidities, directly affecting life expectancy. WAT is the main organ responsible for energy storage, in the form of lipids. But also act as an endocrine organ being able to respond to metabolic changes. Therefore, it promotes changes in whole metabolism leading to the development of IR and an increased cardiometabolic risk. Additionally, the WAT is distributed into two depots: SAT and VAT, each with its own biochemical features and metabolic functions. It has been described that SAT has a protective role it is inversely associated with glucose intolerance, IR, and risk of T2D diagnosis. At the same time VAT is linked with a worsening of metabolic status. WAT is an organ composed by heterogeneous population of cells including pre-adipocytes, fibroblasts, endothelial cells, stem cells and immune cells which changes according to metabolic status. The immune cells regulate WAT function, which is disrupted in obesity, promoting inflammatory signalling which lead to inflammatory, hypoxic, and fibrotic events in WAT. Because the WAT-infiltrated macrophages are the most abundant immune population in WAT, its contribute to a highest proportion to the disruption of homeostasis in obese WAT. However, little is known about which genes or pathways are altered in whole VAT compared to SAT, which promote the development of metabolic diseases. For thus, the objective of this work was determining gene targets that contribute to a worse metabolic prognosis to find its possible role in the development of obesity, related with each depot and infiltrating macrophages. We show for the first time that the phenotype of macrophages infiltrating in WAT have a different gene expression profile according to the depot. Our work proposes novel targets involved in obesity and related metabolic diseases.[spa] La obesidad es una condición crónica cuya incidencia se ha triplicado en las últimas cuatro décadas. Esta condición está asociada a una activación de la respuesta proinflamatoria de las células inmunes infiltradas en el WAT, lo que puede conducir a diferentes comorbilidades, afectando directamente la esperanza de vida. El WAT es órgano principal de almacenamiento de lípidos, pero también actúa como un órgano endocrino pudiendo responder a cambios metabólicos. Por lo tanto, cambios en este tejido puede conducir el desarrollo de comorbilidades asociadas a obesidad. El WAT se distribuye en dos depósitos: SAT y VAT, cada uno con sus propias funciones metabólicas. Se ha descrito que la SAT tiene un papel protector y se asocia inversamente con el desarrollo de IR y T2D. Al mismo tiempo, el VAT está relacionado con un empeoramiento del estado metabólico. Este tejido, está compuesto por una población heterogénea de células que incluyen preadipocitos, fibroblastos, células endoteliales, células madre y células inmunitarias que cambian según el estado metabólico. Las células inmunitarias regulan la función del WAT, que, en condición de obesidad, promueven la activación de la una señalización inflamatoria, hipóxica y fibrótica en este tejido. Debido a que los ATMs son la población inmune más abundante contribuyen en una proporción más alta a la alteración de la homeostasis en WAT en sujetos obesos. Actualmente existe poca información respecto a vías de señalización alteradas en VAT en respecto a SAT asociadas al desarrollo de enfermedades metabólicas. Por ello, el objetivo de este trabajo fue determinar dianas genéticas que contribuyan a un peor pronóstico metabólico para encontrar su posible papel en el desarrollo de la obesidad. Nuestro trabajo muestra por primera vez que el fenotipo de ATMs tienen un perfil de expresión génica diferente según el depósito estudiado. Nuestro trabajo propone nuevas dianas implicadas en la obesidad y enfermedades metabólicas relacionadas

Overnutrition in Infants Is Associated With High Level of Leptin, Viral Coinfection and Increased Severity of Respiratory Infections: A Cross-Sectional Study

Objective: To investigate the relationship of overnutrition (obese and overweight) with severity of illness in children hospitalized with acute lower respiratory infections (ALRIs), frequency of viral coinfections and leptin levels. Methods: We studied 124 children <2 years old that were hospitalized for ALRI. Nutritional status was calculated by z-scores according to weight-for-age z-scores, length or height-for-age z-scores, and weight-for-height z-scores. Nasopharyngeal aspirates (NPAs) were obtained and viral respiratory pathogens were identified using reverse transcription polymerase chain reactions (RT-PCR). Respiratory syncytial virus (RSV) load was assessed using quantitative RT-PCR. NPA and plasma leptin level were measured. Clinical data and nutritional status were recorded, and patients were followed up until hospital discharge. Viral coinfection was defined as the presence of two or more viruses detected in the same respiratory sample. Severity of illness was determined by length of hospitalization and duration of oxygen therapy. Results: Children with overnutrition showed a greater frequency of viral coinfection than those with normal weight (71% obese vs. 37% normal weight p = 0.013; 68% overweight vs. 37% normal weight p = 0.004). A lower RSV load was found in obese (5.91 log(10) copies/mL) and overweight children (6.49 log(10) copies/mL) compared to normal weight children (8.06 log(10) copies/mL; p = 0.021 in both cases). In multivariate analysis, obese, and overweight infants <6 months old were associated with longer hospital stays (RR = 1.68; CI: 1.30-2.15 and obese: RR = 1.68; CI: 1.01-2.71, respectively) as well as a greater duration of oxygen therapy (RR = 1.80; IC: 1.41-2.29 and obese: RR = 1.91; CI: 1.15-3.15, respectively). Obese children <6 months showed higher plasma leptin level than normal weight children (7.58 vs. 5.12 ng/mu l; p <0.046). Conclusions: In infants younger than 6 months, overnutrition condition was related to increased severity of infections and high plasma leptin level. Also, children with overnutrition showed a greater frequency of viral coinfection and low RSV viral load compared to normal weights children. These findings further contribute to the already existent evidence supporting the importance of overnutrition prevention in pediatric populations.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1115059

Quercetin prevents diastolic dysfunction induced by a high-cholesterol diet: role of oxidative stress and bioenergetics in hyperglycemic rats

Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE) against the damage induced by a high-cholesterol (HC) diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio), prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1 alpha, UCP2, and PPAR. expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.FONDECYT 11130232 115111

Pulp, Leaf, Peel and Seed of Avocado Fruit: A Review of Bioactive Compounds and Healthy Benefits

Avocado (Persea americana Mill) is a native American fruit. Its industrial processing generates a large number of wastes (leaves, peels, and seeds). These wastes are a source of bioactive compounds which have been attributed biological activities. We aim to compile scientific research on bioactive compounds of avocado pulp and wastes and their potential biological properties. Main bioactive compounds identified in pulp and wastes are polyphenols, carotenoids, tocopherols, and phytosterols. Thus, wastes extracts have reported numerous biological activities, e.g., antimicrobial, anti-inflammatory, anticancer, antidiabetic, antihypertensive. Therefore, potential applications in food and pharmaceutical industries can be issued.Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECYT 1113037

A polyphenol-rich Calafate (Berberis microphylla) extract rescues glucose tolerance in mice fed with cafeteria diet

The establishment of a chronic inflammatory state in the adipose tissue contributes to obesity-associated insulin resistance. Hence, disrupting the inflammatory response elicited by obesity remains a relevant target to tackle the modern-world pandemic. We evaluated the anti-inflammatory and insulin-sensitizing effect of Calafate (Berberis microphylla) by producing and characterizing a polyphenol-pure Calafate extract (PPCE). C57BL/6 mice fed with cafeteria diet for 14 weeks were administered PPCE (50 mg/Kg/day) for 4 weeks. PPCE administration rescued glucose tolerance and insulin-elicited AKT phosphorylation in white adipose tissue of diet-induced insulin-resistant mice. Furthermore, the cafeteria diet-induced expression of TNF-alpha and F4/80 was attenuated by PPCE administration, suggesting that PPCE rescues insulin sensibility by ameliorating the obesity-associated inflammatory state. Altogether, our data shows that Calafate represents a natural source of polyphenols with glucose tolerance-improving properties in vivo, suggesting a potential use of PPCE as a complementary tool against insulin resistance.CONICYT Scholarship (Chile) 21120219 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1111021