Fabio Bessa Lima

Adipose tissue as an endocrine organ: from theory to practice

OBJECTIVE To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity. SOURCES Important information was compiled from the scientific literature in order that this analysis contains an explanatory synthesis of the aspects mentioned above. SUMMARY OF THE FINDINGS In addition to its classical functions as primary metabolic energy store, meeting energy requirements during periods of deprivation by means of lypolisis, adipose tissue also has the capacity to synthesize and secrete a variety of hormones - the adipokines. These are active in a range of processes, such as control of nutritional intake (leptin) and control of sensitivity to insulin and inflammatory processes (TNF-alpha, IL-6, resistin, visfatin, adiponectin). Furthermore, since adipose tissue also contains undifferentiated cells, it has the ability to generate new adipocytes, regenerating its own tissue (adipogenesis), and also the ability to give rise to other cells (myoblasts, chondroblasts, osteoblasts), which has great therapeutic potential in the not-too-distant future. CONCLUSIONS The range of functional possibilities of adipose tissue has widened. An understanding of these potentials could make this tissue a great ally in the fight against conditions that are currently assuming epidemic proportions (obesity, diabetes mellitus, arterial hypertension and arteriosclerosis) and in which adipose tissue is still seen as the enemy.

O tecido adiposo como centro regulador do metabolismo

The recent progress in the research about the metabolic properties of the adipose tissue and the discovery of its ability to produce hormones that are very active in pathophysiologic as well as physiologic processes is rebuilding the concepts about its biology. Its involvement in conditions like obesity, type 2 diabetes mellitus, arterial hypertension, arteriosclerosis, dislipidemias and chronic and acute inflammatory processes indicate that the understanding of its functional capacities may contribute to improve the prognosis of those diseases whose prevalence increased in a preoccupying manner. Here we review some functional aspects of adipocytes, such as the metabolism, its influence on energy homeostasis, its endocrine ability and the adipogenesis, i.e., the potential of pre-adipocytes present in adipose tissue stroma to differentiate into new adipocytes and regenerate the tissue. In addition, we are including some studies on the relationship between the adipose tissue and the pineal gland, a new and poorly known, although, as will be seen, very promising aspect of adipocyte physiology together with its possible favorable repercussions to the therapy of the obesity related diseases.

O tecido adiposo como órgão endócrino: da teoria à prática

OBJETIVOS Mostrar os avancos na pesquisa sobre o papel fisiologico do tecido adiposo branco, ressaltando o seu papel endocrino em processos inflamatorios, no comportamento alimentar, na sensibilizacao a insulina e na modulacao do processo de aterogenese. Abordar o potencial papel do tecido adiposo como fonte de celulas-tronco para regeneracao de tecidos, com especial enfase para a adipogenese e suas consequencias para a geracao de obesidade. FONTES DE DADOS: Informacoes importantes constantes da literatura cientifica foram compiladas de modo a que esta leitura contenha uma sintese esclarecedora dos aspectos mencionados acima. SINTESE DOS DADOS:O tecido adiposo possui, alem das suas funcoes classicas como principal estoque de energia metabolica, suprindo as necessidades energeticas em periodos de carencia mediante a lipolise, a capacidade de sintetizar e secretar varios hormonios, as adipocinas. Estas agem em diversos processos, como o controle da ingestao alimentar (leptina) e o controle da sensibilidade a insulina e de processos inflamatorios (TNF-alfa, IL-6, resistina, visfatina, adiponectina). Alem disso, como o tecido adiposo contem tambem celulas indiferenciadas, tem a habilidade de gerar novos adipocitos, regenerando o proprio tecido (adipogenese), bem como originar outras celulas (mioblastos, condroblastos, osteoblastos), fato este que tem grande potencial terapeutico em futuro nao muito distante. CONCLUSAO: Amplia-se o leque de possibilidades funcionais do tecido adiposo. A compreensao dessas potencialidades pode fazer deste tecido o grande aliado no combate de molestias que atualmente vem assumindo proporcoes epidemicas (obesidade, diabetes melito, hipertensao arterial e arteriosclerose), nas quais o tecido adiposo ainda e tido como um grande vilao. OBJECTIVES: To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity. SOURCES: Important information was compiled from the scientific literature in order that this analysis contains an explanatory synthesis of the aspects mentioned above. SUMMARY OF THE FINDINGS In addition to its classical functions as primary metabolic energy store, meeting energy requirements during periods of deprivation by means of lypolisis, adipose tissue also has the capacity to synthesize and secrete a variety of hormones - the adipokines. These are active in a range of processes, such as control of nutritional intake (leptin) and control of sensitivity to insulin and inflammatory processes (TNF-alpha, IL-6, resistin, visfatin, adiponectin). Furthermore, since adipose tissue also contains undifferentiated cells, it has the ability to generate new adipocytes, regenerating its own tissue (adipogenesis), and also the ability to give rise to other cells (myoblasts, chondroblasts, osteoblasts), which has great therapeutic potential in the not-too-distant future. CONCLUSIONS: The range of functional possibilities of adipose tissue has widened. An understanding of these potentials could make this tissue a great ally in the fight against conditions that are currently assuming epidemic proportions (obesity, diabetes mellitus, arterial hypertension and arteriosclerosis) and in which adipose tissue is still seen as the enemy.

Melatonin and the circadian entrainment of metabolic and hormonal activities in primary isolated adipocytes.

Abstract:  The aim of this work was to investigate the effect of the in vitro circadian‐like exposure to melatonin [in the presence or absence of insulin (Ins)] on the metabolism and clock gene expression in adipocytes. To simulate the cyclic characteristics of the daily melatonin profile, isolated rat adipocytes were exposed in a circadian‐like pattern to melatonin added to the incubating medium for 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day) combined or not with Ins. This intermittent incubation was interrupted when four and a half 24‐hr cycles were fulfilled. At the end, either during the induced night (melatonin present) or the induced day (melatonin absent), the rates of lipolysis and D‐[U‐14C]‐glucose incorporation into lipids were estimated, in addition to the determination of lipogenic [glucose‐6‐phosphate dehydrogenase and fatty acid synthase (FAS)] and lipolytic (hormone sensitive lipase) enzymes and clock gene (Bmal‐1b, Clock, Per‐1 and Cry‐1) mRNA expression. The leptin release was also measured. During the induced night, the following effects were observed: an increase in the mRNA expression of Clock, Per‐1 and FAS; a rise in lipogenic response and leptin secretion; and a decrease in the lipolytic activity. The intermittent exposure of adipocytes to melatonin temporally and rhythmically synchronized their metabolic and hormonal function in a circadian fashion, mimicking what is observed in vivo in animals during the daily light–dark cycle. Therefore, this work helps to clarify the physiological relevance of the circadian pattern of melatonin secretion and its interactions with Ins, contributing to a better understanding of the adipocyte biology.

Physical Characterization and Electrochemical Activity of Bimetallic Platinum-Silver Particles for Oxygen Reduction in Alkaline Electrolyte

Bimetallic Pt-Ag particles dispersed on a carbon powder (Pt-Ag/C) with 1:1, 1:2, 1:3, and 1:10 (atomic ratio) Pt:Ag were investigated as electrocatalysts for the oxygen reduction reaction (ORR) in alkaline media. These materials were characterized by X-ray diffraction, in situ X-ray absorption near-edge structure, and extended X-ray absorption fine structure. The electrochemical activity for the ORR was evaluated from steady-state polarization measurements in a rotating ring-disk system and in gas diffusion electrodes (EDG). The results showed that the Pt-Ag particles are formed by a core composed by true Pt-Ag alloys, with the surface covered by a Ag-rich layer. An increase of the particle size and of the fcc unit cell lattice parameter with the increase of Ag content was observed. The electrochemical measurements indicated lower activity for the Pt-Ag/C particles compared to Pt/C, but higher activity compared to Ag/C. A number of electrons close to 4 was observed for the ORR in the Pt-Ag/C materials. A discussion of the catalytic activity of the Pt-Ag materials was made in terms of the electronic properties of the Pt and Ag atoms and the morphological structure of the particles.

High dietary sodium intake increases white adipose tissue mass and plasma leptin in rats.

Objective: Salt restriction has been reported to increase white adipose tissue (WAT) mass in rodents. The objective of this study was to investigate the effect of different sodium content diets on the lipogenic and lipolytic activities of WAT.

Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPβ transcriptional activity

Abstract:  Considering that melatonin has been implicated in body weight control, this work investigated whether this effect involves the regulation of adipogenesis. 3T3‐L1 preadipocytes were induced to differentiate in the absence or presence of melatonin (10−3 m). Swiss‐3T3 cells ectopically and conditionally (Tet‐off system) over‐expressing the 34 kDa C/EBPβ isoform (Swiss‐LAP cells) were employed as a tool to assess the mechanisms of action at the molecular level. Protein markers of the adipogenic phenotype were analyzed by Western blot. At 36 hr of differentiation of 3T3‐L1 preadipocytes, a reduction of PPARγ expression was detected followed by a further reduction, at day 4, of perilipin, aP2 and adiponectin protein expression in melatonin‐treated cells. Real‐time PCR analysis also showed a decrease of PPARγ (60%), C/EBPα (75%), adiponectin (30%) and aP2 (40%) mRNA expression. Finally, we transfected Swiss LAP cells with a C/EBPα gene promoter/reporter construct in which luciferase expression is enhanced in response to C/EBPβ activity. Culture of such transfected cells in the absence of tetracycline led to a 2.5‐fold activation of the C/EBPα promoter. However, when treated with melatonin, the level of C/EBPα promoter activation by C/EBPβ was reduced by 50% (P = 0.05, n = 6). In addition, this inhibitory effect of melatonin was also reflected in the phenotype of the cells, since their capacity to accumulate lipids droplets was reduced as confirmed by the poor staining with Oil Red O. In conclusion, melatonin at a concentration of 10−3  m works as a negative regulator of adipogenesis acting in part by inhibiting the activity of a critical adipogenic transcription factor, C/EBPβ.

Electrochemical performance of dispersed Pt-M (M =V, Cr and Co) nanoparticles for the oxygen reduction electrocatalysis

A cinetica da reacao de reducao de oxigenio (RRO) foi estudada em eletrolito de KOH em eletrodos de camada ultra fina, formados por eletrocatalisadores de Pt-V, Pt-Cr e Pt-Co dispersos em po de carbono (Pt-M/C). As caracteristicas eletronicas e estruturais dos eletrocatalisadores foram estudadas por XANES (X-ray Absorption Near Edge Structure) e EXAFS (Extended X-ray Absorption Fine Structure) in situ. Voltametria ciclica e curvas de polarizacao do estado estacionario para a RRO foram obtidas usando a tecnica de disco/anel rotatorio. Os resultados de XANES para as ligas no estado oxidado mostraram um aumento na ocupacao da banda 5d da Platina, enquanto que os resultados de EXAFS mostraram uma pequena reducao na distância interatomica Pt-Pt em relacao a Pt/C. As medidas eletroquimicas indicaram que o mecanismo via 4 eletrons e principalmente seguido para a RRO nas ligas de platina. A maior atividade eletrocatalitica foi atingida pela liga Pt-V/ C, depois de tratamento termico a 850 o C em atmosfera de hidrogenio. The kinetics of the oxygen reduction reaction (ORR) was studied in KOH electrolyte on ultra thin layer electrodes formed by Pt-V, Pt-Cr and Pt-Co electrocatalysts dispersed on a carbon powder (Pt-M/C). The electronic and structural features of the materials were studied by in situ XANES (Xray Absorption Near Edge Structure) and EXAFS (Extended X-ray Absorption Fine Structure). Cyclic voltammograms and steady state polarization curves for the ORR were obtained using the rotating ring/disk electrode technique. The XANES results for the composites in the oxidized state have shown an increase of the occupancy of the Pt 5d band while the EXAFS analyses showed some reduction of the Pt-Pt interatomic distance in the different metal alloys compared to Pt/C. The electrochemical measurements indicated that the 4-electrons mechanism is mainly followed for the ORR in these platinum alloys. The highest electrocatalytic activity was shown by the Pt-V/C alloy, after treated at 850 o C under hydrogen atmosphere.

Electrocatalytic Properties of PtCo ∕ C and PtNi ∕ C alloys for the Oxygen Reduction Reaction in Alkaline Solution

The oxygen reduction reaction (ORR) was studied on carbon-dispersed Pt 3 Co, PtCo, and Pt 3 Ni alloys in KOH electrolyte. A detailed discussion of the enhancement of the O 2 reduction kinetics based on the physical and electronic properties of the catalysts is presented. The characterization techniques considered were high-resolution transmission electron microscopy, XRD (X-ray diffraction), in situ XANES (X-ray absorption near edge structure), and EXAFS (extended X-ray absorption fine structure) measurements. Cyclic voltammetry and steady-state polarization measurements for the ORR were conducted using a rotating ring-disk electrode. The XANES results at the Pt L 3 edge at anodic potentials showed lower oxide coverage on the PtCo/C catalysts, while at the Co and Ni K edges the results evidenced compositions that include Co or Ni metals and oxides. The XRD and EXAFS analyses showed a slight reduction of the Pt-Pt interatomic distance in the Pt alloys compared to Pt/C. The polarization curves indicated that the 4-electron mechanism is mainly followed for the ORR on all materials. The highest electrocatalytic activity was obtained for the PtCo/C alloy (1:1 atomic ratio), and this was attributed to less Pt-OH formation or faster Pt-O - electroreduction due to a lower Pt d-band center.

Nonelectrochemical Pathway of Methanol Oxidation at a Platinum-Catalyzed Oxygen Gas Diffusion Electrode

Potentiostatic investigations of the methanol oxidation in the absence and presence of oxygen at the three-phase boundary of a Pt-catalyzed gas diffusion electrode were carried out at several electrode potentials. In the presence of oxygen, a purely chemical reaction between oxygen and methanol was observed, with the products being CO 2 and water. A study of the rate of CO 2 formation and of the electrochemical currents for methanol oxidation showed that the rate of fuel consumption at the electrode is strongly increased by this chemical pathway. This is accompanied by a considerable decrease in the electrochemical currents for oxygen reduction. In the absence of oxygen and for potentials above 1.1 V vs. RHE, current oscillations were observed during the anodic process, which were attributed to the formation of an unstable layer of surface platinum oxides.