Shivering unlocks new way of fighting fat

Shivering is not an activity many of us enjoy. We do it because we are cold and uncomfortable. But perhaps the news that it could have some of the same benefits as moderate bouts of exercise will stop us running in from the cold so quickly. Researchers have found that the act of shivering can stimulate the conversion of energy-storing “white fat” into energy-burning “brown fat”

HIV-1 Infection and the PPARγ-Dependent Control of Adipose Tissue Physiology

PPARγ is a ligand-dependent master transcription factor controlling adipocyte differentiation as well as multiple biological processes taking place in other cells present in adipose tissue depots such as macrophages. Recent research indicates that HIV-1 infection-related events may alter adipose tissue biology through several mechanisms involving PPARγ, ranging from direct effects of HIV-1-encoded proteins on adipocytes to the promotion of a proinflammatory environment that interferes with PPARγ actions. This effect of HIV-1 on adipose tissue cells can occur even in the absence of direct infection of adipocytes, as soluble HIV-1-encoded proteins such as Vpr may enter cells and inhibit PPARγ action. Moreover, repression of PPARγ actions may relieve inhibitory pathways of HIV-1 gene transcription, thus enhancing HIV-1 effects in infected cells. HIV-1 infection-mediated interference of PPARγ-dependent pathways in adipocytes and other cells inside adipose depots such as macrophages is likely to create an altered local environment that, after antiretroviral treatment, leads to lipodystrophy in HIV-1-infected and HAART-treated patients

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

A Differential Pattern of Batokine Expression in Perivascular Adipose Tissue Depots From Mice

Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the mesenteric arteries and the caudal part of abdominal aorta is similar to white fat. PVAT is thought to influence vascular function through the effects of adipose-secreted molecules on vessels. Brown adipose tissue was recently shown to play differential secretory role via secretion of the so-called batokines but the involvement of differential batokine production in PVAT brown/ beige plasticity was unclear. The current study characterizes for the first time the expression of batokines at aortic thoracic PVAT (tPVAT) and aortic abdominal PVAT (aPVAT) in comparison with typical brown and white adipose depots, in basal and thermogenically activated conditions. We found that both PVAT depots increased their expression of genes encoding the batokines bone morphogenetic protein-8b (BMP8B), fibroblast growth factor-21 (FGF21), and kininogen-2 (KNG2) in response to cold, indicating that, under cold-induced thermogenic activation, both thoracic aorta and abdominal aorta would experience intense local exposure to these PVAT-secreted batokines. In contrast, the gene expression levels of growth/differentiation factor-15 and vascular endothelial growth factor-A were induced only in tPVAT. Under short-term high-fat diet-induced thermogenic activation, the thoracic aorta would be specifically exposed to a local increase in PVAToriginating BMP8B, FGF21, and KNG2. Our data support the notion that acquisition of a brown/beige phenotype in PVAT is associated with upregulation of batokines, mainly BMP8B, FGF21, and KNG2, that can differentially target the vascular system

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

Graph generation to statically represent CSP processes

The CSP language allows the specification and verification of complex concurrent systems. Many analyses for CSP exist that have been successfully applied in different industrial projects. However, the cost of the analyses performed is usually very high, and sometimes prohibitive, due to the complexity imposed by the non-deterministic execution order of processes and to the restrictions imposed on this order by synchronizations. In this work, we define a data structure that allows us to statically simplify a specification before the analyses. This simplification can drastically reduce the time needed by many CSP analyses. We also introduce an algorithm able to automatically generate this data structure from a CSP specification. The algorithm has been proved correct and its implementation for the CSP's animator ProB is publicly available. © 2011 Springer-Verlag.This work has been partially supported by the Spanish Ministerio de Ciencia e Innovación under grant TIN2008-06622-C03-02, by the Generalitat Valenciana under grant ACOMP/2010/042, and by the Universidad Politécnica de Valencia (Program PAID-06-08). Salvador Tamarit was partially supported by the Spanish MICINN under FPI grant BES-2009-015019.Llorens Agost, ML.; Oliver Villarroya, J.; Silva Galiana, JF.; Tamarit Muñoz, S. (2011). Graph generation to statically represent CSP processes. En Logic-Based Program Synthesis and Transformation. Springer Verlag (Germany). 6564:52-66. https://doi.org/10.1007/978-3-642-20551-4_4S52666564Brassel, B., Hanus, M., Huch, F., Vidal, G.: A Semantics for Tracing Declarative Multi-paradigm Programs. In: Moggi, E., Warren, D.S. (eds.) 6th ACM SIGPLAN Int’l Conf. on Principles and Practice of Declarative Programming (PPDP 2004), pp. 179–190. ACM, New York (2004)Butler, M., Leuschel, M.: Combining CSP and B for specification and property verification. In: Fitzgerald, J., Hayes, I.J., Tarlecki, A. (eds.) FM 2005. LNCS, vol. 3582, pp. 221–236. Springer, Heidelberg (2005)Hoare, C.A.R.: Communicating Sequential Processes. Prentice-Hall, Upper Saddle River (1985)Kavi, K.M., Sheldon, F.T., Shirazi, B., Hurson, A.R.: Reliability Analysis of CSP Specifications using Petri Nets and Markov Processes. In: 28th Annual Hawaii Int’l Conf. on System Sciences (HICSS 1995). Software Technology, vol. 2, pp. 516–524. IEEE Computer Society, Washington, DC, USA (1995)Ladkin, P., Simons, B.: Static Deadlock Analysis for CSP-Type Communications. In: Responsive Computer Systems (Ch. 5). Kluwer Academic Publishers, Dordrecht (1995)Leuschel, M., Butler, M.: ProB: an Automated Analysis Toolset for the B Method. Journal of Software Tools for Technology Transfer 10(2), 185–203 (2008)Leuschel, M., Llorens, M., Oliver, J., Silva, J., Tamarit, S.: Static Slicing of CSP Specifications. In: Hanus, M. (ed.) 18th Int’l Symp. on Logic-Based Program Synthesis and Transformation (LOPSTR 2008), pp. 141–150. Technical report, DSIC-II/09/08, Universidad Politécnica de Valencia (July 2008)Leuschel, M., Llorens, M., Oliver, J., Silva, J., Tamarit, S.: SOC: a Slicer for CSP Specifications. In: Puebla, G., Vidal, G. (eds.) 2009 ACM SIGPLAN Symposium on Partial Evaluation and Semantics-based Program Manipulation (PEPM 2009), pp. 165–168. ACM, New York (2009)Leuschel, M., Llorens, M., Oliver, J., Silva, J., Tamarit, S.: The MEB and CEB static analysis for CSP specifications. In: Hanus, M. (ed.) LOPSTR 2008. LNCS, vol. 5438, pp. 103–118. Springer, Heidelberg (2009)Llorens, M., Oliver, J., Silva, J., Tamarit, S.: A Semantics to Generate the Context-sensitive Synchronized Control-Flow Graph (extended). Technical report DSIC, Universidad Politécnica de Valencia, Valencia, Spain (June 2010), http://www.dsic.upv.es/~jsilvaLlorens, M., Oliver, J., Silva, J., Tamarit, S.: Transforming Communicating Sequential Processes to Petri Nets. In: Topping, B.H.V., Adam, J.M., Pallarés, F.J., Bru, R., Romero, M.L. (eds.) Seventh Int’l Conference on Engineering Computational Technology (ICECT 2010). Civil-Comp Press, Stirlingshire, UK, Paper 26 (2010)Roscoe, A.W., Gardiner, P.H.B., Goldsmith, M., Hulance, J.R., Jackson, D.M., Scattergood, J.B.: Hierarchical Compression for Model-Checking CSP or How to Check 1020 Dining Philosophers for Deadlock. In: Brinksma, E., Cleaveland, R., Larsen, K.G., Margaria, T., Steffen, B. (eds.) TACAS 1995. LNCS, vol. 1019, pp. 133–152. Springer, Heidelberg (1995)Roscoe, A.W.: The Theory and Practice of Concurrency. Prentice Hall, Upper Saddle River (2005

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

A Semantics to Generate the Context-sensitive Synchronized Control-Flow Graph (extended)

The CSP language allows the specification and verification of complex concurrent systems. Many analyses for CSP exist that have been successfully applied in different industrial projects. However, the cost of the analyses performed is usually very high, and sometimes prohibitive, due to the complexity imposed by the non-deterministic execution order of processes and to the restrictions imposed on this order by synchronizations. In this work, we define a data structure that allows us to statically simplify a specification before the analyses. This simplification can dras- tically reduce the time needed by many CSP analyses. We also introduce an algorithm able to automatically generate this data structure from a CSP specification. The algorithm has been proved correct and its implementation for the CSP's animator ProB is publicly available.Tamarit Muñoz, S.; Silva Galiana, JF.; Llorens Agost, ML.; Oliver Villarroya, FJ. (2010). A Semantics to Generate the Context-sensitive Synchronized Control-Flow Graph (extended). http://hdl.handle.net/10251/839

Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling

The spread of bacterial resistance to antimicrobials (AMA) have intensified efforts to discontinue the non-therapeutic use of AMA in animal production. Finding alternatives to AMA, however, is currently encumbered by the obscure mechanism that underlies their growth-promoting action. In this report, we demonstrate that combinations of antibiotics and zinc oxide at doses commonly used for stimulating growth or preventing post-weaning enteritis in pigs converge in promoting microbial production of bile acids (BA) in the intestine. This leads to tissue-specific modifications in the proportion of BA, thereby amplifying BA signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA-regulated pathways ultimately reinforces the intestinal protection against bacterial infection and pathological secretion of fluids and electrolytes, attenuates inflammation in colon and WAT, alters protein and lipid metabolism in liver, and increases the circulating levels of the hormone FGF19. Conceivably, these alterations could spare nutrients for growth and improve the metabolic efficiency of AMA-treated animals. This work provides evidence that BA act as signaling molecules that mediate host physiological, metabolic, and immune responses to the AMA-induced alterations in gut microbial metabolism, eventually permitting the growth-promoting action of AMA. Consequently, BA emerge as a promising target for developing efficacious alternatives to AMA