Secretory Proteome of Brown Adipocytes in Response to cAMP-Mediated Thermogenic Activation

Background: The secretory properties of brown adipose tissue are thought to contribute to the association between active brown fat and a healthy metabolic status. Although a few brown adipokines have been identified, a comprehensive knowledge of the brown adipose tissue secretome is lacking.Methods: Here, to examine the effects of thermogenic activation of brown adipocytes on protein secretion, we used isobaric tags for relative and absolute quantification (iTRAQ) analysis to determine how the secreted proteome of brown adipocytes (that detected in cell culture medium) differed in response to cAMP.Results: Our results indicated that 56 secreted proteins were up-regulated in response to cAMP. Of them, nearly half (29) corresponded to extracellular matrix components and regulators. Several previously known adipokines, were also detected. Unexpectedly, we also found five components of the complement system. Only 15 secreted proteins were down-regulated by cAMP; of them three were ECM-related and none was related to the complement system. We observed a partial concordance between the cAMP-regulated release of proteins (both from proteomics and from antibody-based quantification of specific proteins) and the cAMP-mediated regulation of their encoding transcript for the up-regulated secreted proteins. However, a stronger concordance was seen for the down-regulated secreted proteins.Conclusions: The present results highlight the need to investigate previously unrecognized processes such as the role of extracellular matrix in thermogenic activation-triggered brown fat remodeling, as well as the intriguing question of how brown adipocyte-secreted complement factors contribute to the signaling properties of active brown adipose tissue

Oncostatin m impairs brown adipose tissue thermogenic function and the browning of subcutaneous white adipose tissue

© 2016 The Obesity Society Objective: Since oncostatin m (OSM) is elevated in adipose tissue in conditions of obesity and type 2 diabetes in mice and humans, the aim of this study was to determine whether this cytokine plays a crucial role in the impairment of brown adipose tissue (BAT) activity and browning capacity that has been observed in people with obesity. Methods: C57BL/6J mice rendered obese by high-fat diet, their lean controls, and C57BL/6J mice fed a standard diet and implanted subcutaneously with a mini pump through a surgical procedure to deliver OSM or placebo were used. Preadipocytes or fully differentiated brown adipocytes were treated with OSM or vehicle with or without norepinephrine before harvesting. RNA was extracted and processed for qPCR analysis. Media from mature adipocytes was also collected to measure glycerol levels. Results: Studies demonstrated that OSM gene expression was increased in BAT of mice fed a high-fat diet. In addition, exogenous OSM impaired BAT activity and the browning capacity of white adipose tissue in vitro and in vivo. Conclusions: Overall, the results reveal a negative role for OSM on BAT and on the browning of white adipose tissue. Therefore, further studies are necessary to demonstrate whether OSM inhibition is a potential treatment for metabolic disorders

Altered GDF15 and FGF21 Levels in Response to Strenuous Exercise: A Study in Marathon Runners

Background: Recreational marathon runners face strong physiological challenges. Assessment of potential biomarkers for the biological responses of runners will help to discriminate individual race responsiveness and their physiological consequences. This study sought to analyze the changes in the plasma levels of GDF15 and FGF21, novel endocrine factors related to metabolic stress, in runners following the strenuous exercise of a marathon race. Methods: Blood samples were obtained from eighteen male runners (mean ±SD, age: 41.7 ±5.0 years, BMI: 23.6 ± 1.8) 48 h before, immediately after, and 48 h after a marathon race, and from age-matched sedentary individuals. The level of GDF15, FGF21, and 38 additional biochemical and hematological parameters were determined. Results: The basal levels of GDF15 and FGF21 did not differ between runners before the race and sedentary individuals. Significant increases in the mean levels of GDF15 (4.2-fold) and FGF21 (20-fold) were found in runners immediately after the race. The magnitudes of these increases differed markedly among individuals and did not correlate with each other. The GDF15 and FGF21 levels had returned to the basal level 48 h post-race. The post-race value of GDF15 (but not FGF21) correlated positively with increased total white cell count (r = 0.50, P = 0.01) and neutrophilia (r = 0.10, P = 0.01). Conclusion: GDF15 and FGF21 are transiently increased in runners following a marathon race. The induction of GDF15 levels is associated with alterations in circulating immune cells levels

Bone Morphogenetic Protein-8B levels at birth and in the first year of life: relation to metabolic-endocrine variables and brown adipose tissue activity

Objective: Bone morphogenetic protein-8B (BMP8B) is an adipokine produced by brown adipose tissue (BAT) contributing to thermoregulation and metabolic homeostasis in rodent models. In humans, BAT activity is particularly relevant in newborns and young infants. We assessed BMP8B levels and their relationship with BAT activity and endocrine-metabolic parameters in young infants to ascertain its potentiality as biomarker in early life. Methods and Materials: BMP8B concentrations were assessed longitudinally by ELISA in a cohort of 27 girls and 23 boys at birth, and at age 4 and 12 months, together with adiposity parameters (DXA), and circulating endocrine-metabolic variables. BAT activity was measured by infrared thermography. BMP8B gene expression (qRT-PCR) was determined in BAT, white fat, and liver samples from neonatal necropsies, and in placenta and cord blood. Results: BMP8B levels were high at birth, particularly in boys (P=0.04 vs girls), declined progressively, and remained well above those in healthy adults and pregnant women at age one year (P<0.05 and P<0.001, respectively). Neonatal BMP8B transcript levels were higher in BAT than in white fat, liver and cord blood. Circulating BMP8B levels during the first year of life marginally correlated with bone mineral density and gains in lean mass. Conclusion: BMP8B levels are high at birth and decline progressively over the first year of life remaining above adult levels. Although changes in BMP8B concentrations overall reflect those in BAT activity during development, BMP8B levels are unlikely to be useful to predict individual variations in endocrine-metabolic status and BAT activity in healthy young infants

The kallikrein-kinin pathway as a mechanism for auto-control of brown adipose tissue activity

Brown adipose tissue (BAT) is known to secrete regulatory factors in response to thermogenic stimuli. Components of the BAT secretome may exert local effects that contribute to BAT recruitment and activation. Here, we found that a thermogenic stimulus leads to enhanced secretion of kininogen (Kng) by BAT, owing to induction of kininogen 2 (Kng2) gene expression. Noradrenergic, cAMP-mediated signals induce KNG2 expression and release in brown adipocytes. Conversely, the expression of kinin receptors, that are activated by the Kng products bradykinin and [Des-Arg9]-bradykinin, are repressed by thermogenic activation of BAT in vivo and of brown adipocytes in vitro. Loss-of-function models for Kng (the circulating-Kng-deficient BN/Ka rat) and bradykinin (pharmacological inhibition of kinin receptors, kinin receptor-null mice) signaling were coincident in showing abnormal overactivation of BAT. Studies in vitro indicated that Kng and bradykinin exert repressive effects on brown adipocyte thermogenic activity by interfering the PKA/p38 MAPK pathway of control of Ucp1 gene transcription, whereas impaired kinin receptor expression enhances it. Our findings identify the kallikrein-kinin system as a relevant component of BAT thermogenic regulation that provides auto-regulatory inhibitory signaling to BAT

Adipose tissue aging partially accounts for fat alterations in HIV lipodystrophy

Altres ajuts: European Regional Development Fund (FEDER).Lipodystrophy is a major disturbance in people living with HIV-1 (PLWH). Several systemic alterations in PLWH are reminiscent of those that occur in ageing. It is unknown whether the lipodystrophy in PLWH is the consequence of accelerated ageing in adipose tissue. We compared systemic and adipose tissue disturbances in PLWH with those in healthy elderly individuals (~80 y old). We observed similarly enhanced expression of inflammation-related genes and decreased autophagy in adipose tissues from elderly individuals and PLWH. Indications of repressed adipogenesis and mitochondrial dysfunction were found specifically in PLWH, whereas reduced telomere length and signs of senesce were specific to elderly individuals. We conclude that ageing of adipose tissue accounts only partially for the alterations in adipose tissues of PLWH

Desarrollo de una población con variabilidad genética para la selección de genotipos. con características agronómicas superiores con la asistencia de marcadores moleculares

En Argentina, las variedades de cultivo de algodón disponibles en el mercado presentan valores de rendimiento de fibra al desmote que van desde 36% a 41%. Esta característica surge de la relación de cantidad de fibra de algodón obtenida en el proceso de desmote y la cantidad de algodón bruto (fibra + semilla) que ingresa a la desmotadora, expresado en porcentaje. Estos rendimientos resultan bajos si se los compara con variedades de otros países productores de algodón como por ejemplo Australia, en los que sus cultivares presentan valores siempre superiores a 40%.EEA ReconquistaFil: Dileo, Pablo Nahuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Muchut, Robertino José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Winkler, Horacio Martín. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Cereijo, Antonela Estefanía. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Scarpin, Gonzalo Joel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Lorenzini, Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Roeschlin, Roxana Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Paytas, Marcelo Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Rodríguez, Gustavo Rubén. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; Argentin

Desarrollo de una población con variabilidad genética para la selección de genotipos con características agronómicas superiores con la asistencia de marcadores moleculares

En Argentina, las variedades de cultivo de algodón disponibles en el mercado presentan valores de rendimiento de fibra al desmote que van desde 36% a 41%. Esta característica surge de la relación de cantidad de fibra de algodón obtenida en el proceso de desmote y la cantidad de algodón bruto (fibra + semilla) que ingresa a la desmotadora, expresado en porcentaje. Estos rendimientos resultan bajos si se los compara con variedades de otros países productores de algodón como por ejemplo Australia, en los que sus cultivares presentan valores siempre superiores a 40%. En este contexto, es necesario propiciar el desarrollo de nuevos genotipos adaptados a las condiciones del Norte de Santa Fe, con mejoras en el rendimiento de fibra al desmote, manteniendo la calidad. Actualmente, desde INTA Reconquista se viene trabajando con diferentes líneas de investigación que proponen combinar estrategias de selección de mejoramiento convencional con técnicas de biotecnología, entre ellas, la de selección asistida por marcadores moleculares.Fil: Dileo, Pablo Nahuel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Winkler, Horacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Cereijo, Antonela Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Muchut, Robertino José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Scarpin, Gonzalo Joel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Lorenzini, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Roeschlin, Roxana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Paytas, Marcelo Javier. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Rodríguez, Gustavo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; Argentin

A role for Oncostatin M in the impairment of glucose homeostasis in obesity

CONTEXT: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels 100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance