Papel de la célula grasa en el riesgo cardiovascular / Role of the fat cell in cardiovascular risk

Resumen La obesidad es una enfermedad crónica, no transmisible, que recientemente ha tenido una connotación especial debido al aumento de su prevalencia en países en vía de desarrollo. Este incremento está relacionado con un aumento en la aparición de enfermedades metabólicas y el riesgo cardiovascular. Si bien la prevalencia de obesidad está aumentando en todos los países del mundo, existen diferencias regionales tanto en la prevalencia como en las tendencias de la obesidad. Por consiguiente, comprender los impulsores de estas diferencias regionales podría ayudar a proporcionar orientación para las estrategias de intervención más prometedoras. A pesar de considerarse una eventualidad simple en una proporción de lo que se ingiere y lo que se gasta, existen muchos factores que regulan esta enfermedad. No es sencillo encontrar medidas terapéuticas para la obesidad, pues sus causas son múltiples. En forma reciente, ha despertado un especial interés la caracterización funcional de los adipocitos, específicamente de los adipocitos beige, dado que su función está íntimamente relacionada con las circunstancias externas del ambiente y tienen una flexibilidad que les permite producir energía y mejorar muchos de los parámetros metabólicos en los individuos. En este manuscrito se hará énfasis en las características de las células adiposas y su influencia en el riesgo cardiovascular.

Abstract Obesity is a chronic non-transmissible disease that has recently had a special connotation due to the increase of its prevalence in developing countries. The increase in obesity is related to an expansion in the appearance of metabolic diseases and cardiovascular risk. Although the prevalence of obesity is increasing in all countries of the world, there are regional differences in both the prevalence and trends of obesity. Therefore, understanding the circumstances of these regional differences could help provide guidance for the most promising intervention strategies. Despite being considered a simple outcome in a proportion of what is ingested and what is spent, there are many factors that regulate this disease. It is not easy to find therapeutic measures for obesity, because their causes are multiple. Recently, the functional characterization of adipocytes, especially Beige adipocytes, has been of particular interest since their function is intimately related to the external circumstances of the environment and they have a flexibility that allows them to produce energy and improve many of the metabolic parameters in individuals. In the present manuscript we will focus on the characteristics of fat cells and their influence on cardiovascular risk.

Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions

BACKGROUND: Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (T(reg)) expression under intermittent hypobaric conditions. METHODS: Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of T(regs) (CD4 + CD25 + Foxp3 + T cells), cytokines [tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined. RESULTS: Splenocytes, cultured with brown and white adipocytes, exhibited comparable T(reg) expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of T(regs). However, a decrease in T(regs) was found in the white adipocyte group. TNF-α levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions. CONCLUSION: Both brown and white adipocytes support T(reg) expression when they are cultured with splenocytes. Of note, brown adipocytes maintained T(reg) expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.

Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive inflammation. Recently, RA associated with a metabolic disorder was revealed to be non-responsive to RA medications. Metformin has been reported to have a therapeutic effect on RA and obesity. The aim of this investigation was to study the therapeutic effect and the underlying mechanism of metformin's action in an experimental model of collagen-induced arthritis (CIA) associated with obesity. Metformin was administered daily for 13 weeks to mice with CIA that had been fed a high-fat diet. Metformin ameliorated the development of CIA in obese mice by reducing autoantibody expression and joint inflammation. Furthermore, metformin decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing effect on the metabolic profile of obese CIA mice. In addition, metformin increased the production of pAMPK and FGF21. Metformin also induced the differentiation of brown adipose tissue (BAT), which led to a reciprocal balance between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo. These results suggest that metformin can dampen the development of CIA in obese mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus, metformin could be a therapeutic candidate for non-responsive RA.

Intraosseous Hibernoma: A Rare and Unique Intraosseous Lesion

BACKGROUND: Hibernoma is a rare benign tumor of adults that is composed of multivacuolated adipocytes resembling brown fat cells. Hibernoma typically occurs in soft tissue, and intraosseous examples are very rare. Intraosseous hibernomas can radiologically mimic metastatic carcinoma and other tumorous conditions. METHODS: To collect the intraosseous hibernomas, we searched the pathologic database and reviewed the hematoxylin and eosin (H&E)–stained slides of bone biopsy samples performed to differentiate radiologically abnormal bone lesions from 2006 to 2016. A total of six intraosseous hibernoma cases were collected, and clinical and radiological information was verified from electronic medical records. H&E slide review and immunohistochemical staining for CD68, pan-cytokeratin, and S-100 protein were performed. RESULTS: Magnetic resonance imaging of intraosseous hibernomas showed low signal intensity with slightly hyperintense foci on T1 and intermediate to high signal intensity on T2 weighted images. Intraosseous hibernomas appeared as heterogeneous sclerotic lesions with trabecular thickening on computed tomography scans and revealed mild hypermetabolism on positron emission tomography scans. Histopathologically, the bone marrow space was replaced by sheets of multivacuolated, foamy adipocytes resembling brown fat cells, without destruction of bone trabeculae. In immunohistochemical analysis, the tumor cells were negative for CD68 and pan-cytokeratin and positive for S-100 protein. CONCLUSIONS: Intraosseous hibernoma is very rare. This tumor can be overlooked due to its rarity and resemblance to bone marrow fat. Pathologists need to be aware of this entity to avoid misdiagnosis of this rare lesion.

The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes

BACKGROUND: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. METHODS: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. RESULTS: RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. CONCLUSION: RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.

Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders

Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.

Letter: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes (Endocrinol Metab 2016;31:328-35, Cheol Ryong Ku et al.)

No abstract available.

Response: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes (Endocrinol Metab 2016;31:328-35, Cheol Ryong Ku et al.)

No abstract available.

Effect of bone morphogenetic protein 7 on differentiation of adipose derived mesenchymal stem cells into brown adipocytes in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effect of bone morphogenetic protein(BMP7)on the differentiation of adipose derived mesenchymal stem cells(AD-MSCs)isolated from different adipose tissues into brown adipocytes in rats.</p><p><b>METHODS</b>Primary AD-MSCs were isolated from rate interscapular brown adipose tissue(iBAT),inguinal subcutaneous white adipose tissue(sWAT),and epididymal white adipose tissue(eWAT),respectively,and then cultivated in vitro. Differentiation of AD-MSCs into brown adipocytes was induced by BMP7. The characteristics of brown adipocytes were detected by immunofluorescence staining and oil red staining of cells. The expression levels of brown adipocyte-related genes were detected by polymerase chain reaction.</p><p><b>RESULTS</b>AD-MSCs from iBAT and sWAT were differentiated into cluster multilocular cells,which were stained red by oil red "O"staining and showed uncoupling protein 1-positive by immunofluorescent staining method. AD-MSCs from eWAT had a small number of scattered multilocular cells and showed uncoupling protein 1-negative. The results of reverse transcription-polymerase chain reaction showed that the uncoupling protein 1 gene was highly expressed in the iBAT group and sWAT group but was negative in the eWAT group.</p><p><b>CONCLUSION</b>AD-MSCs isolated from different adipose tissues in rats have different gene expression profiles and differentiation potentials.</p>

The Mechanism of White and Brown Adipocyte Differentiation

Obesity gives vent to many diseases such as type 2 diabetes, hypertension, and hyperlipidemia, being considered as the main causes of mortality and morbidity worldwide. The pathogenesis and pathophysiology of metabolic syndrome can well be understood by studying the molecular mechanisms that control the development and function of adipose tissue. In human body, exist two types of adipose tissue, the white and the brown one, which are reported to play various roles in energy homeostasis. The major and most efficient storage of energy occurs in the form of triglycerides in white adipose tissue while brown adipose tissue actively participates in both basal and inducible energy consumption in the form of thermogenesis. Recent years have observed a rapid and greater interest towards developmental plasticity and therapeutic potential of stromal cells those isolated from adipose tissue. The adipocyte differentiation involves a couple of regulators in the white or brown adipogenesis. Peroxisome proliferators-activated receptor-gamma actively participates in regulating carbohydrate and lipid metabolism, and also acts as main regulator of both white and brown adipogenesis. This review based on our recent research, seeks to highlight the adipocyte differentiation.

Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics

Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 microM) and partially by quetiapine (30 microM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPbeta, PPARgamma2, UCP-1, PGC-1alpha, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARgamma2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 microM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.

Hibernoma do couro cabeludo / Hibernoma of the hairy scalp

O hibernoma constitui-se em tumor benigno raro, derivado de gordura marrom que usualmente se manifesta como massa de crescimento lento e indolor. Este relato descreve a presença de hibernoma localizado no couro cabeludo em paciente adulta, feminino.

Hibernoma is a rare benign tumor of brown fat origin which usually manifests as a slowly growing, pain- less, soft-tissue mass. This case report describes the presence of hibernoma located on the scalp in an adult woman, female.

Imprint Cytology of Hibernoma: A Case Report / 대한세포병리학회지

Hibernoma is a rare, benign adipose tumor composed of brown fat cells with eosinophilic granular or multivacuolated cytoplasm. The cytologic features of hibernoma have been rarely reported and may mimic other polygonal cell neoplasms. We report the imprint cytologic features of a case of hibernoma in the left thigh of a 68-year-old woman. Microscopic examination showed large, round, or polygonal brown fat cells. The cells were arranged in fragments or clusters. The nuclei were uniformly round with finely granular chromatin. The cytoplasm was multivacuolated or univacuolated. The abundant eosinophilic granular cytoplasm was also present. No nuclear atypia were present. Immunohistochemical staining showed that cells were positive for S-100 protein.