La tormentosa relación entre las grasas y el desarrollo de la diabetes mellitus de tipo 2: actualizado. Parte 1 / The stormy relationship between fats and the development of type 2 diabetes mellitus: An Update. Part 1

Se describe la relación funcional del metabolismo de las grasas y los hidratos de carbono y su interdependencia, desde los tradicionales conceptos del ciclo glucosa-ácidos grasos (Randle) y la hipótesis portal de la insulinorresistencia hasta los nuevos sobre los adipocitos marrones y beiges, con énfasis en el normal funcionamiento de un patrón endocrino cuya disfunción es clave en la fisiopatología: el eje adipoinsular, vinculado funcionalmente incluso con el hipotálamo, la hipófisis y las adrenales, que involucra 2 hormonas adipogénicas (insulina y glucocorticoide) que facilitarían el desarrollo de la grasa omental perivisceral, con fuertes consecuencias metabólicas. Se discute la ectopia o asiento de grasa en tejido magro por incapacidad del tejido adiposo para seguir atesorando grasas y la actividad endocrina del adipocito, con la producción de moléculas que influyen sobre los mecanismos productores de insulinorresistencia (leptina, adiponectina, TNF-α, resistina, etc.) y disfunción insular. Se describe la disminución de la capacidad oxidativa en la cadena respiratoria mitocondrial y el renacer del concepto de lipogénesis de novo, ambas favorecedoras del atesoramiento de grasas intracelular. En tejidos magros existen pequeñas reservas intracelulares de grasas que mantienen una regulación de funciones esenciales, aunque si aparece una sobrecarga lipídica, el fenómeno conduciría a disfunción (lipotoxicidad) y muerte celular (lipoapoptosis). La tormentosa relación entre las grasas y el islote de Langerhans va más allá del esfuerzo funcional que impone la insulinorresistencia periférica sobre la célula β, por efectos directos de los lípidos o sus derivados sobre la función del islote pancreático. Sin déficit de insulina no hay diabetes.

A review is presented on a functional relationship between fat and carbohydrate metabolism and inter-dependence from the traditional concepts of glucose-fatty acids cycle (Randle), and from the insulin resistance portal hypothesis up to the new aspects on brown and beige adipocytes. Emphasis is placed on the normal function of an endocrine pattern, in which its malfunction is the key in the pathophysiology of these conditions: the adipoinsular axis, with a functional link with the hypothalamic-pituitary-adrenal axis, which involves 2 adipogenic hormones (insulin and glucocorticoid). This has an influence on the development of omental peri-visceral fat, with severe metabolic consequences. A discussion is also presented on the concept of ectopic fat on non-adipose tissues that results in the incapacity of fatty tissue for storing lipids and the considerations about the endocrine activity of adipocyte producing substances that influence several mechanisms that could result in insulin resistance (leptin, adiponectin, TNF-α, resistin, etc.). New aspects are considered regarding the decrease in the oxidative capacity in the mitochondrial respiratory chain, and the rebirth of the concept of de novo lipogenesis that increases the storing of intra-cellular fat. In non-adipose tissues there are small intra-cellular fat quantities for essential functions, but lipid overloading leads to cell dysfunction (lipo-toxicity) and death (lipo-apoptosis). The stormy relationship between fat and Langerhans' Islets goes beyond the functional effort as consequence of peripheral insulin-resistance and the pancreatic beta cell suffers a direct lipid (or derivatives) functional effect. Without insulin deficiency diabetes does not appear.

Expression regulation and functional analysis of RGS2 and RGS4 in adipogenic and osteogenic differentiation of human mesenchymal stem cells

BACKGROUND: Understanding the molecular basis underlying the formation of bone-forming osteocytes and lipid-storing adipocytes will help provide insights into the cause of disorders originating in stem/progenitor cells and develop therapeutic treatments for bone- or adipose-related diseases. In this study, the role of RGS2 and RGS4, two members of the regulators of G protein signaling (RGS) family, was investigated during adipogenenic and osteogenenic differentiation of human mesenchymal stem cells (hMSCs). RESULTS: Expression of RGS2 and RGS4 were found to be inversely regulated during adipogenesis induced by dexamethasone (DEX) and 3-isobutyl-methylxanthine, regardless if insulin was present, with RGS2 up-regulated and RGS4 down-regulated in response to adipogenic induction. RGS2 expression was also up-regulated during osteogenesis at a level similar to that induced by treatment of DEX alone, a shared component of adipogenic and osteogenic differentiation inducing media, but significantly lower than the level induced by adipogenic inducing media. RGS4 expression was down-regulated during the first 48 h of osteogenesis but up-regulated afterwards, in both cases at levels similar to that induced by DEX alone. Expression knock-down using small interfering RNA against RGS2 resulted in decreased differentiation efficiency during both adipogenesis and osteogenesis. On the other hand, expression knock-down of RGS4 also resulted in decreased adipogenic differentiation but increased osteogenic differentiation. CONCLUSIONS: RGS2 and RGS4 are differentially regulated during adipogenic and osteogenic differentiation of hMSCs. In addition, both RGS2 and RGS4 play positive roles during adipogenesis but opposing roles during osteogenesis, with RGS2 as a positive regulator and RGS4 as a negative regulator. These results imply that members of RGS proteins may play multifaceted roles during human adipogenesis and osteogenesis to balance or counterbalance each other's function during those processes.

Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69; p<0.01). Marrow adipose tissue was not significantly increased in patients (CG = 32.8±11.2% vs PHPT = 38.6±12%). The serum levels of osteocalcin were higher in patients (CG = 8.6±3.6 ng/mL vs PHPT = 36.5±38.4 ng/mL; p<0.005), but no associations were observed between osteocalcin and insulin or between insulin and both marrow adipose tissue and bone mass. CONCLUSION: These results suggest that the increment of adipogenesis in the bone marrow microenvironment under conditions of high bone turnover due to primary hyperparathyroidism is limited. Despite the increased serum levels of osteocalcin due to primary hyperparathyroidism, these patients tend to have impaired insulin sensitivity.

Aging impairs osteoblast differentiation of mesenchymal stem cells grown on titanium by favoring adipogenesis

ABSTRACT Aging negatively affects bone/titanium implant interactions. Our hypothesis is that the unbalance between osteogenesis and adipogenesis induced by aging may be involved in this phenomenon. Objective We investigated the osteoblast and adipocyte differentiation of mesenchymal stem cells (MSCs) from young and aged rats cultured on Ti. Material and Methods Bone marrow MSCs derived from 1-month and 21-month rats were cultured on Ti discs under osteogenic conditions for periods of up to 21 days and osteoblast and adipocyte markers were evaluated. Results Cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene expression of RUNX2, osterix, ALP, bone sialoprotein, osteopontin, and osteocalcin were reduced in cultures of 21-month rats compared with 1-month rats grown on Ti. Gene expression of PPAR-γ , adipocyte protein 2, and resistin and lipid accumulation were increased in cultures of 21-month rats compared with 1-month rats grown on the same conditions. Conclusions These results indicate that the lower osteogenic potential of MSCs derived from aged rats compared with young rats goes along with the higher adipogenic potential in cultures grown on Ti surface. This unbalance between osteoblast and adipocyte differentiation should be considered in dental implant therapy to the elderly population.

New concepts in white adipose tissue physiology

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

La redistribución dinámica mitocondria-núcleo de la inmunofilina FKBP51 es regulada por pka para modular la expresión de genes durante el proceso de adipogénesis / [The dynamic mitochondria-nuclear redistribution of FKBP51 during the process of adipocyte differentiation is regulated by PKA].

Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90-Hsp70 and a high molecular weight immunophilin FKBP51 or FKBP52. We have found that FKBP51 level of expression progressively increases, FKBP52 decreases, whereas Hsp90, Hsp70, and p23 remain unchanged when 3T3-L1 preadipocytes differentiate. Interestingly, FKBP51 translocates from mitochondria to the nucleus at the onset of adipogenesis. FKBP51 transiently concentrates in the nuclear lamina, at a time that this nuclear compartment undergoes its reorganization. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. We found that the dynamic FKBP51 mitochondrial-nuclear shuttling is regulated by glucocorticoids and mainly on cAMP-PKA signaling since PKA inhibition by myristoilated-PKI, abrogated FKBP51 nuclear translocation induced by 3-isobutyl-1-methylxanthine (IBMX). It has been reported that PKA interacts with GR in a ligand dependent manner potentiating its transcriptional capacity. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutyryl-cAMP, compounds that induced nuclear translocation of FKBP51, therefore PKA may exert a dual role in the control of GR. In summary, the presence of FKBP51 in the nucleus may be critical for GR transcriptional control, and possibly for the control of other transcription factors that are not members of the nuclear receptor family but are regulated by PKA signaling pathway, when transcription has to be strictly controlled to succeed in the acquisition of the adipocyte phenotype.

In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis

The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.

Células-tronco derivadas de tecido adiposo humano: desafios atuais e perspectivas clínicas / Human adipose-derived stem cells: current challenges and clinical perspectives

As células-tronco adultas ou somáticas detêm grande promessa para a reparação e regeneração de tecidos. Atualmente, o interesse dos cientistas é contínuo na investigação da biologia de células-tronco mesenquimais, tanto em aspectos básicos, quanto no potencial de aplicações terapêuticas. As células-tronco adultas derivadas do estroma do tecido adiposo, em comparação com as células-tronco derivadas do estroma da medula óssea, apresentam como vantagem o método fácil de obtenção da fonte tecidual. As células-tronco adultas derivadas do estroma do tecido adiposo apresentam potencial para se diferenciarem em células de tecidos mesodérmicos, como os adipócitos, as cartilagens, os ossos e o músculo esquelético e não mesodérmicos, como os hepatócitos, as células pancreáticas endócrinas, os neurônios, os hepatócitos e as células endoteliais vasculares. Entretanto, os dados disponíveis na literatura científica sobre as características das células-tronco adultas derivadas do estroma do tecido adiposo e os procedimentos para sua obtenção e manipulação no laboratório são inconsistentes. É necessário o desenvolvimento de metodologias e procedimentos eficazes de isolamento dessas células para obtenção de células em quantidade e qualidade suficientes para aplicação terapêutica. Nesta revisão, são discutidos os métodos correntes de coleta de tecido adiposo, isolamento e caracterização de células-tronco adultas derivadas do estroma do tecido adiposo, com ênfase na futura aplicação em medicina regenerativa e nos possíveis desafios nesse recente campo da ciência.

Adult or somatic stem cells hold great promise for tissue regeneration. Currently, one major scientific interest is focused on the basic biology and clinical application of mesenchymal stem cells. Adipose tissue-derived stem cells share similar characteristics with bone marrow mesenchymal stem cells, but have some advantages including harvesting through a less invasive surgical procedure. Moreover, adipose tissue-derived stem cells have the potential to differentiate into cells of mesodermal origin, such as adipocytes, cartilage, bone, and skeletal muscle, as well as cells of non-mesodermal lineage, such as hepatocytes, pancreatic endocrine cells, neurons, cardiomyocytes, and vascular endothelial cells. There are, however, inconsistencies in the scientific literature regarding methods for harvesting adipose tissue and for isolating, characterizing and handling adipose tissue-derived stem cells. Future clinical applications of adipose tissue-derived stem cells rely on more defined and widespread methods for obtaining cells of clinical grade quality. In this review, current methods in adipose tissue-derived stem cell research are discussed with emphasis on strategies designed for future applications in regenerative medicine and possible challenges along the way.

Controle da adipogênese por ácidos graxos: [revisão] / Control of adipogenesis by fatty acids: [review]

A obesidade é um dos principais problemas de saúde pública. Indivíduos obesos são mais suscetíveis a desenvolver doenças cardiovasculares e diabetes melito tipo 2. A obesidade resulta do aumento no tamanho e no número de adipócitos. O balanço entre adipogênese e adiposidade determina o grau de obesidade do indivíduo. Adipócitos maduros secretam adipocinas, tais como TNFα, IL-6, leptina e adiponectina, e lipocina, o ácido palmitoleico ω-7. A produção de adipocinas é maior na obesidade, o que contribui para o estabelecimento de resistência periférica à insulina. O conhecimento dos eventos moleculares que regulam a diferenciação dos pré-adipócitos e de células-tronco mesenquimais em adipócitos (adipogênese) é importante para o entendimento da gênese da obesidade. A ativação do fator de transcrição PPARγ é essencial na adipogênese. Certos ácidos graxos são ligantes de PPARγ e podem, assim, controlar a adipogênese. Além disso, alguns ácidos graxos atuam como moléculas sinalizadoras em adipócitos, regulando sua diferenciação ou morte. Dessa forma, a composição lipídica da dieta e os agonistas de PPARγ podem regular o balanço entre adipogênese e morte de adipócitos e, portanto, a obesidade.

Obesity is one of the major Public Health problems. Obese individuals are more susceptible to develop cardiovascular diseases and type 2 diabetes mellitus. The obesity results from the increase in size and number of the adipocytes. The balance between adipogenesis and adiposity determines the degree of obesity. Mature adipocytes secrete adipokines, such as TNFα, IL-6, leptine and adiponectin, and lipokine, the palmitoleic acid ω-7. The production of adipokines is increased in obesity, contributing to the onset of peripheral insulin resistance. The knowledge about the molecular events that regulate the differentiation of pre-adipocytes and mesenchymal stem cells into adipocytes (adipogenesis) is important for the comprehension of the genesis of obesity. Activation of transcription factor PPARγ plays an essential role in the adipogenesis. Certain fatty acids are PPARγ ligands and can control adipogenesis. Moreover, some fatty acids act as signaling molecules regulating their differentiation into adipocytes or death. Accordingly, the lipid composition of the diet and PPARγ agonists can regulate the balance between adipogenesis and death of adipocytes and, therefore, the obesity.

Adipogénesis y osteoporosis: [revisión] / Adipogenesis and osteoporosis: [review]

Mesenchymal stem cells (MSCs) found in bone marrow stroma, are able to differentiate into osteoblasts and adipocytes, among other cellphenotypes. In normal bone marrow balance osteoblastic an adipocytes cell differentiation favour bone formation, while in osteoporosis there is an increased adipocytes content. Since osteoblasts and adipocytes originate from a common MSC precursor cell, here we discuss whether quantitative and qualitative stem cell defects may be the cause of alterations in the number and function of differentiated cells. This review analyzes some conditions that contribute to different osteogenic/adipogenic potentials in human bone marrow MSCs obtained from control and osteoporotic postmenopausal women. We analyze the protective effect exerted by locally generated factors like estradiol and leptin on MSCs differentiation, because altered bioavailability of these factors may play a role in osteoporosis. Osteoporotic MSCs (o-MSCs) are characterized by increased adipogenic potential as compared to control cells. Leptin exerted a direct protective action against adiposeness only in control cells. In contrast, leptin action on o-MSCs is hampered, suggesting that inadequate leptin action may be associated to lipid accumulation in bone marrow.

Infeccions as the etiology for obesity / Infecções na etiologia da obesidade

The role of infection on obesity development has been questioned since the early 1980's. Several studies on animals have shown that fisiopathologic mechanisms through which infections can produce obesity do exist. At least eight types of obesity-inducing viruses have been identified in animals, especially poultry and mice. Studies on humans are far less convincing; however, two adenoviruses, Ad-36 and SMAM-1, have shown adipogenic properties. In vitro studies with 3T3-L1 cells stated the activation of the enzymatic pathway that leads to fatty tissue accumulation; in vivo studies have also detected higher levels of antibodies against such viruses on obese subjects. Although most known infections nowadays cause obesity through central nervous system lesions, the Ad-36 adenovirus infection affects fatty tissue directly, raising doubts regarding central role component in this case.

Desde o início dos anos 1980, o papel das infecções tem sido debatido quanto à etiologia da obesidade. Diversos estudos em modelos animais têm demonstrado que mecanismos fisiopatológicos ativados pelas infecções podem induzir também à obesidade. Pelo menos oito tipos de obesidade induzidas por viroses foram caracterizadas em animais, especialmente em camundongos e galinhas. Estudos em humanos existem, mas são menos convincentes. No entanto, duas adenoviroses (Ad-36 e SMAN-1) apresentam características adipogênicas. Estudos in vitro com a linhagem celular 3T3-L1 demonstraram que ativações enzimáticas levam ao acúmulo de gordura celular. Estudos in vivo detectaram níveis elevados de anticorpos contra certas viroses especialmente em indivíduos obesos. A maioria das infecções potenciais causadoras de obesidade atua produzindo ativações ou lesões no sistema nervoso central. Por outro lado, a infecção por Ad-36 adenovírus afeta diretamente o tecido adiposo, expandindo dessa forma a etiologia viral da obesidade para mecanismos hipotalâmicos e periféricos.

O tecido adiposo como órgão endócrino: da teoria à prática: [revisão] / Adipose tissue as an endocrine organ: from theory to practice: [review]

OBJETIVOS Mostrar os avanços na pesquisa sobre o papel fisiológico do tecido adiposo branco, ressaltando o seu papel endócrino em processos inflamatórios, no comportamento alimentar, na sensibilização à insulina e na modulação do processo de aterogênese. Abordar o potencial papel do tecido adiposo como fonte de células-tronco para regeneração de tecidos, com especial ênfase para a adipogênese e suas conseqüências para a geração de obesidade. FONTES DE DADOS: Informações importantes constantes da literatura científica foram compiladas de modo a que esta leitura contenha uma síntese esclarecedora dos aspectos mencionados acima. SÍNTESE DOS DADOS:O tecido adiposo possui, além das suas funções clássicas como principal estoque de energia metabólica, suprindo as necessidades energéticas em períodos de carência mediante a lipólise, a capacidade de sintetizar e secretar vários hormônios, as adipocinas. Estas agem em diversos processos, como o controle da ingestão alimentar (leptina) e o controle da sensibilidade à insulina e de processos inflamatórios (TNF-alfa, IL-6, resistina, visfatina, adiponectina). Além disso, como o tecido adiposo contém também células indiferenciadas, tem a habilidade de gerar novos adipócitos, regenerando o próprio tecido (adipogênese), bem como originar outras células (mioblastos, condroblastos, osteoblastos), fato este que tem grande potencial terapêutico em futuro não muito distante. CONCLUSÃO: Amplia-se o leque de possibilidades funcionais do tecido adiposo. A compreensão dessas potencialidades pode fazer deste tecido o grande aliado no combate de moléstias que atualmente vêm assumindo proporções epidêmicas (obesidade, diabetes melito, hipertensão arterial e arteriosclerose), nas quais o tecido adiposo ainda é tido como um grande vilão.

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.

MicroRNAs: nova classe de reguladores gênicos envolvidos na função endócrina e câncer / MicroRNAs: novel class of gene regulators involved in endocrine function and cancer / MicroRNAs: novel class of gene regulators involved in endocrine function and cancer

MicroRNAs (miRNAs) representam uma nova classe de RNAs endógenos de ~22 nucleotídeos, que atuam como silenciadores pós-transcricionais, inibindo a tradução de RNAs mensageiros-alvo. Descobertos há pouco mais de uma década em Caenorhabditis elegans, os miRNAs são hoje reconhecidos como reguladores fundamentais da expressão gênica em plantas e animais. Até o momento, identificaram-se 462 genes de miRNA no genoma humano e estima-se que esse número supere 1000 miRNAs distintos. Análises bioinformáticas indicam que um único miRNA atue em diversos RNAs mensageiros, influenciando múltiplas vias de sinalização concomitantemente e apresentando enorme potencial regulatório. Apesar da biologia dos miRNAs ser ainda pouco entendida, essas moléculas já foram relacionadas a diversos processos biológicos. Além disso, a expressão anômala destes pequenos RNAs tem sido associada a diferentes patologias humanas, inclusive aquelas relacionadas ao sistema endócrino e câncer.

MicroRNAs (miRNAs) represent a novel class of endogenous ~22-nucleotide RNAs that negatively regulate gene expression by inhibiting translation of target RNAs. Discovered just over a decade ago in Caenorhabditis elegans, miRNAs are now recognized as one of the major regulatory gene families in plants and animals. In the human genome, 462 miRNA genes have been discovered and the estimated number of miRNAs is as high as 1000. Bioinformatics analysis indicated that a unique miRNA acts on several mRNA, influencing multiple signaling pathways concomitantly, thus presenting enormous regulatory potential. Although the biology of miRNAs is not well understood, recent evidences have linked these molecules to diverse biological processes. Moreover, aberrant expression of miRNAs has been associated to human disease, including that related to the endocrine system and cancer.

O tecido adiposo como centro regulador do metabolismo / The adipose tissue as a regulatory center of the metabolism

Os avanços da pesquisa sobre as propriedades metabólicas do tecido adiposo e as recentes descobertas sobre sua capacidade em produzir hormônios atuantes em processos fisiológicos e fisiopatológicos, estão revolucionando conceitos sobre a sua biologia. O seu envolvimento em processos como obesidade, diabetes mellitus tipo 2, hipertensão arterial, arteriosclerose, dislipidemias, processos inflamatórios agudos e crônicos, entre outros, indicam que a compreensão das suas propriedades funcionais contribuirão para melhorar o prognóstico daquelas doenças, cuja prevalência vem crescendo de forma preocupante. Nesta revisão, abordamos aspectos funcionais dos adipócitos, como o metabolismo, a participação na homeostase energética, a sua habilidade endócrina e a adipogênese, entendida como a capacidade de pré-adipócitos, presentes no parênquima do tecido, de se diferenciarem em novos adipócitos e reconstituírem o tecido. Além disso, estamos incluindo estudos sobre as relações entre o tecido adiposo e a glândula pineal, aspecto novo e pouco conhecido, mas, como será visto, muito promissor da fisiologia do adipócito com possíveis repercussões favoráveis para a terapêutica das moléstias relacionadas com a obesidade.

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.