Efecto de la dieta CAF sobre la capacidad de EX4 de modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis en músculo de ratones / Effect of the CAF diet on the ability of EX4 to modulate the expression of protein markers of fatty acid oxidation and thermogenesis in mouse muscle

El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.

The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.

Histamine stimulates thermogenesis of brown and beige fat / 生理学报

β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.

Thermoregulatory and perceptual responses of lean and obese fit and unfit girls exercising in the heat / Respostas termorregulatórias e perceptivas de meninas magras e obesas com alta e baixa aptidão aeróbica exercitando-se no calor

Abstract Objective: To verify the thermoregulatory and perceptual responses of obese and lean girls, either fit or unfit, exercising in the heat at a similar rate of metabolic heat production per unit body mass. Methods: A total of 34 pubescent girls were allocated in four groups: 12 obese fit, 9 obese unfit, 5 lean fit, and 8 lean unfit. The obese groups (13.2 ± 1.4 years, 40.5% ± 5.8% fat by DXA) differed in their aerobic fitness (V˙O2peak 76.0 ± 8.1 vs. 56.6 ± 5.8 mL.kg muscle mass-1.min-1), as well as the lean groups (13.1 ± 1.6 years, 24.0% ± 4.8% fat) (V˙O2peak 74.5 ± 2.9 vs. 56.2 ± 5.0 mL.kg muscle mass-1 min-1). Girls cycled two bouts of 25 min with a 10 min rest in between, at ∼5.4 W.kg-1 in the heat (36 °C and 40% relative humidity) and they were kept euhydrated. Rectal and skin temperatures and heart rate were measured every 5 min. Perceptual responses were evaluated throughout the exercise. Results: Initial rectal temperature was higher in the obese subjects compared to the lean subjects (37.5 ± 0.3 and 37.2 ± 0.3 °C). No difference was observed among the girls whom were obese (eight fit or unfit) and lean (also fit or unfit) throughout the exercise in rectal temperature (37.6 ± 0.2, 37.5 ± 0.3, 37.5 ± 0.3, 37.4 ± 0.3 °C, respectively), skin temperature (34.8 ± 0.8, 35.1 ± 1.0, 34.4 ± 0.9, 35.2 ± 0.9 °C), and heart rate (128 ± 18; 118 ± 12, 130 ± 16, 119 ± 16 beats min-1). No differences were observed in perceptual responses among groups. Conclusion: Regardless of the adiposity or aerobic fitness, pubescent girls had similar thermoregulatory and perceptual responses while cycling in the heat at similar metabolic heat production.

Resumo Objetivo: Verificar as respostas termorregulatórias e perceptivas de meninas obesas e magras, com alta e baixa aptidão aeróbica, exercitando-se no calor com produção metabólica de calor similar por massa corporal. Métodos: Um total de 34 meninas púberes foram alocadas em quatro grupos: 12 obesas com alta aptidão aeróbica, 9 obesas com baixa aptidão aeróbica, 5 magras com alta aptidão aeróbica e 8 magras com baixa aptidão aeróbica. Os grupos obesos (13,2 ± 1,4 anos, 40,5% ± 5,8% de gordura por DXA) diferiram em sua aptidão aeróbica (V˙O2peak 76,0 ± 8,1 vs. 56,6 ± 5,8 mL.kg de massa muscular-1.min-1), bem como os grupos magros (13,1 ± 1,6 anos, 24,0% ± 4,8% de gordura) (V˙O2peak 74,5 ± 2,9 vs. 56,2 ± 5,0 mL.kg de massa muscular-1min-1). As meninas pedalaram duas sessões de 25 minutos com descanso de 10 minutos entre as sessões, a ∼5,4 W.kg-1 no calor (36∘C e 40% de umidade relativa) e foram mantidas hidratadas. As temperaturas retal e cutânea e a frequência cardíaca foram medidas a cada 5 minutos. As respostas perceptivas foram avaliadas durante o exercício. Resultados: A temperatura retal inicial foi maior nas meninas obesas em comparação com as magras (37,5 ± 0,3 e 37,2 ± 0,3 °C). Não houve diferença entre as meninas obesas (com alta aptidão aeróbica ou não) e magras (também com alta aptidão aeróbica ou não) durante todo o exercício em relação à temperatura retal (37,6 ± 0,2; 37,5 ± 0,3; 37,5 ± 0,3; 37,4 ± 0,3 °C; respectivamente), temperatura da pele (34,8 ± 0,8; 35,1 ± 1,0; 34,4 ± 0,9; 35,2 ± 0,9 °C), e frequência cardíaca (128 ± 18; 118 ± 12, 130 ± 16, 119 ± 16 batimentos.min-1). Não foram observadas diferenças nas respostas perceptivas entre os grupos. Conclusão: Independentemente da adiposidade ou do condicionamento aeróbico, as meninas púberes tiveram respostas termorregulatórias e perceptivas semelhantes, enquanto pedalavam no calor com uma produção metabólica de calor similar.

Effect of the fatty acid composition of meals on postprandial energy expenditure: a systematic review

SUMMARY The energy imbalance produced by an increase in caloric intake and/or decrease in energy expenditure induces obesity. However, the fatty acid composition of a diet can affect the metabolism in different ways, having a role in the development of obesity. AIM To determine the effect of different fatty acids types and composition on Diet-Induced Thermogenesis (DIT) and postprandial energy expenditure in humans. METHODS A search in the PubMed and Web of Science databases, yielded a total of 269 potential articles as a first result; 254 were excluded according to the criteria. RESULTS Fifteen articles were used for this systematic review. The studies analyzed report different effects of the fatty acids of the treatment on the diet-induced thermogenesis. Evidence indicates that the consumption of polyunsaturated fatty acids causes a greater DIT than saturated fatty acids. Also, the consumption of medium-chain fatty acids compared to long-chain fatty acids has been shown to increase DIT. Likewise, the use of certain oils has shown positive effects on postprandial energy expenditure, as is the case of olive oil, compared to rapeseed oil. CONCLUSIONS The use of specific types of fatty acids in the everyday diet can increase postprandial energy expenditure in humans. Nevertheless, longer-term studies are required.

RESUMO O desequilíbrio energético produzido pelo aumento da ingestão calórica e/ou diminuição do gasto energético provoca obesidade. Sem embargo, a composição de ácidos graxos da dieta pode afetar diferencialmente o metabolismo, tendo um papel no desenvolvimento da obesidade. OBJETIVO Determinar os efeitos de diferentes tipos de ácidos graxos e sua composição na termogênese induzida por dieta e no gasto energético pós-prandial em humanos. MÉTODOS Uma busca nas bases de dados da PubMed e da Web of Science gerou um total de 269 artigos potenciais como primeiro resultado; 254 foram excluídos de acordo com os critérios. RESULTADOS Quinze artigos foram utilizados para esta revisão sistemática. Os estudos analisados informam os efeitos diferenciais dos ácidos graxos no tratamento da termogênese induzida pela dieta. As evidências indicam que o consumo dos ácidos graxos poli-insaturados ocasiona maior DIT que os ácidos graxos saturados. Além disso, demonstra-se que o consumo dos ácidos graxos da cadeia média, em comparação com os ácidos graxos da cadeia longa, aumenta o DIT. Do mesmo modo, o uso de certos azeites demonstra os efeitos positivos sobre o gasto de energia pós-prandial, como é o caso do azeite de oliva, em comparação com o azeite de colza. CONCLUSÃO O uso de tipos específicos de ácidos graxos na dieta habitual pode aumentar o gasto de energia pós-prandial nos seres humanos. Sem embargo, é necessária maior investigação no longo prazo.

Efecto antimicrobiano de la terapia fotodinámica versus la terapia láser sobre la Porphyromona gingivalis: Estudio in vitro / Efeito antimicrobiano da terapia laser versão daterapia photodinâmica na Porphyromonas gingivalis: Estudo in vitro / Antimicrobial effect of photodynamic therapy versus laser therapy on Porphyromone gingivalis: In vitro study

En la actualidad existen diferentes aplicaciones del láser en Odontología; esta Terapia se basa en la emisión de energía luminosa con diferente longitud de onda dependiendo del procedimiento que se realice generan efectos físicos y químicos que producen repuestas biológicas y terapéuticas como cicatrización de heridas, efectos analgésicos y antiinflamatorios además de inhibir la progresión de gingivitis y periodontitis. Objetivo: Evaluar el efecto antimicrobiano de la Terapia Fotodinámica (TFD) y de la Terapia Láser sobre colonias de Porphyromona Gingivalis (Pg). Materiales y Métodos: Estudio experimental, in vitro. La muestra estuvo constituida por 48 disoluciones de (Pg) que aprox. contiene 1000 colonias, se dividieron en 6 grupos de 8 muestras cada uno siendo: G1: 0.05% Azul de Metileno AM + luz led, G2: 0.1%AM + luz led, G3: 0.05% AM + Laser, G4: 0.1%AM + Laser, G5 Terapia Láser (30") y G6: Terapia Láser (60"). Los datos obtenidos fueron analizados estadísticamente mediante la prueba de Kruskal Wallis y U Mann Whitney con un nivel de significancia de 5%. Resultados: Los valores medios de ufc fueron de 190,1, 187,8, 23,6, 13,1, 2,1 y 0,0 para G1, G2, G3, G4, G5 y G6 respectivamente. Obteniéndose una significancia (p<0,001) que permitió inferir que la capacidad antimicrobiana fue distinta para los diferentes protocolos empleados. Conclusión: La TFD con láser y el uso del Láser fueron más efectivas que la TFD con luz led en la reducción de colonias bacterianas (Pg).

At present there are different applications of the laser in Dentistry; This Therapy is based on the emission of luminous energy with different wavelengths. Depending on the procedure performed, they generate physical and chemical effects that produce biological and therapeutic responses such as wound healing, analgesic and anti-inflammatory effects, as well as inhibiting the progression of gingivitis and periodontitis. Objective: To evaluate the antimicrobial effect of Photodynamic Therapy (PDT) and Laser Therapy on colonies of Porphyromona Gingivalis (Pg). Materials and Methods: Experimental study, in vitro. The sample consisted of 48 solutions of (Pg) that approx. contains 1000 colonies, were divided into 6 groups of 8 samples each being: G1: 0.05% Methylene blue AM + led light, G2: 0.1% AM + led light, G3: 0.05% AM + Laser, G4: 0.1% AM + Laser, G5 Laser Therapy (30 ") and G6: Laser Therapy (60"). The data obtained were statistically analyzed by the Mann Whitney U test with a level of significance of 5%. Results: The mean cfu values were 190.1, 187.8, 23.6, 13.1, 2.1 and 0.0 for G1, G2, G3, G4, G5 and G6 respectively. obtained a Significance (p <0.001) that allowed us to infer that the antimicrobial capacity was different for the different protocols used. Conclusion: The PDT with laser and the use of the laser were more effective than the PDT with led light in the reduction of bacterial colonies (Pg).

Atualmente existem diferentes aplicações do laser na Odontologia; esta terapia baseia-se na emissão de energia luminosa com comprimentos de onda diferentes, dependendo do procedimento realizado geram efeitos físicos e químicos que produzem respostas biológicas e terapêuticas como cicatrização de feridas, efeitos analgésicos e anti-inflamatórios além de inibir a progressão da gengivite e periodontite. Objetivo: Avaliar o efeito antimicrobiano da Terapia Fotodinâmica (TFD) e Laser Therapy em colônias de Porphyromona Gingivalis (Pg). Materiais e Métodos: Estudo experimental, in vitro. A amostra foi composta por 48 soluções de (Pg) que aprox. contém 1000 colônias, foram divididos em 6 grupos de 8 amostras sendo: G1: 0,05% azul de metileno AM + luz led, G2: 0,1% AM + luz led, G3: 0,05% AM + Laser, G4: 0,1% AM + Laser, Terapia Laser G5 (30 ") e G6: Terapia Laser (60"). Os dados obtidos foram analisados estatisticamente pelos testes de Kruskal Wallis e U Mann Whitney, com nível de significância de 5%. Resultados: Os valores médios de ufc foram 190,1, 187,8, 23,6, 13,1, 2,1 e 0,0 para G1, G2, G3, G4, G5 e G6, respectivamente. Obteve-se significância (p <0,001) que permitiu inferir que a capacidade antimicrobiana foi diferente para os diferentes protocolos utilizados. Conclusão: A TFD com laser e o uso de laser foram mais efetivos que TFD com luz LED na redução de colônias bacterianas (Pg).

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia / 医学前沿

Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BATactivation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.

Regulation of adiposity by mTORC1 / Controle da adiposidade por mTORC1

ABSTRACT Obesity is characterized by an excessive increase in the adipose tissue mass, and is associated with higher incidence of several chronic metabolic diseases, such as type 2 diabetes. Therefore, its increasing prevalence is a public health concern, and it is important to better understand its etiology to develop new therapeutic strategies. Evidence accumulated over the years indicates that obesity is associated with a marked activation in adipose tissue of the mechanistic target of rapamycin complex 1 (mTORC1), a signaling pathway that controls lipid metabolism, and adipocyte formation and maintenance. Curiously, mTORC1 is also involved in the control of nonshivering thermogenesis and recruitment as well as browning of white adipose tissue. In this review, we explored mTORC1 functions in adipocytes and presented evidence, suggesting that mTORC1 may either increase or reduce adiposity, depending on the conditions and activation levels.

RESUMO A obesidade é caracterizada pelo aumento excessivo da massa de tecido adiposo, estando associada à maior incidência de diversas doenças metabólicas crônicas, como diabetes tipo 2. Sua crescente prevalência é uma questão de saúde pública, e faz-se importante compreender melhor sua etiologia, para desenvolver novas estratégias terapêuticas. As evidências acumuladas por muitos anos indicam que a obesidade está associada à significativa ativação no tecido adiposo do complexo 1 da proteína alvo mecanístico da rapamicina (mTORC1), uma via de sinalização que regula o metabolismo de lipídeos, bem como a formação e manutenção de adipócitos. Curiosamente, mTORC1 também está envolvido no controle da termogênese, independente do tremor muscular, e no recrutamento e browning de tecido adiposo branco. Nesta revisão, exploramos as diferentes funções do mTORC1 em adipócitos e apresentamos evidências que sugerem que o mTORC1 pode aumentar ou reduzir a adiposidade, dependendo das condições e de seu nível de ativação.

Water temperature, body mass and fasting heat production of pacu (Piaractus mesopotamicus)

ABSTRACT Knowledge on fasting heat production (HEf) of fish is key to develop bioenergetics models thus improving feeding management of farmed species. The core of knowledge on HEf of farmed, neotropical fish is scarce. This study assessed the effect of body mass and water temperature on standard metabolism and fasting heat production of pacu, Piaractus mesopotamicus, an omnivore, Neotropical fresh water characin important for farming and fisheries industries all through South American continent. An automated, intermittent flow respirometry system was used to measure standard metabolic rate (SMR) of pacu (17 - 1,050 g) at five water temperatures: 19, 23, 26, 29 and 33 °C. Mass specific SMR increased with increasing water temperature but decreased as function of body mass. The allometric exponent for scaling HEf was 0.788, and lied in the range recorded for all studied warm-water fish. The recorded van't Hoff factor (Q10) for pacu (2.06) shows the species low response to temperature increases. The model HEf = 0.04643×W0.7882×T1.837 allows to predict HEf (kJ d-1) from body mass (W, kg) and water temperature (T, °C), and can be used in bioenergetical models for the species.

[Comparison of moderate and high volume aerobic training on gene expression of uncoupling protein 1 [UCP-1] in subcutaneous white adipose tissue of wistar rats]

Introduction: The aim of this study was to investigate the effect of moderate and high volume aerobic training on the expression of Uncoupling Protein 1[UCP-1] gene in subcutaneous WAT [sub-WAT]

Materials and Methods: Twenty-four rats were assigned randomly into three groups: 1] control [n=8] 2] moderate-volume aerobic training [n=8] and 3] high-volume aerobic training [n=8]. Subjects of training groups underwent continuous aerobic training on the treadmill for 8 weeks, 5 sessions per week at two different volumes of training. The Real Time-PCR method was used to measure the expression ratio of UCP-1 gene

Results: Data showed that although the expression ratio of UCP1 gene in the moderate volume aerobic training group was significantly higher than control group [P=0.014], its expression ratio in the high volume aerobic training group did not differ significantly from controls [P=0.36]; neither was the gene expression ratio different between moderate and high volume aerobic training groups [P=0.59]

Conclusion: Results indicate that moderate volume aerobic training, had an obvious effect in inducing UCP1 gene expression in subcutaneous adipose tissue, while the high volume aerobic training did not. Thus, increasing the volume of aerobic training to high levels may not be a key factor in promoting the non-shivering theremogenesis of sub-WAT

Metronidazole thermogel improves retention and decreases permeation through the skin

ABSTRACT Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex(r) (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex(r). Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex(r), but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex(r), when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex(r) for the topical application of MTZ with improved efficacy and reduced side effects.

Bile Acid Receptor Farnesoid X Receptor: A Novel Therapeutic Target for Metabolic Diseases

Bile acid has been well known to serve as a hormone in regulating transcriptional activity of Farnesoid X receptor (FXR), an endogenous bile acid nuclear receptor. Moreover, bile acid regulates diverse biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism and energy expenditure. Alteration of bile acid metabolism has been revealed in type II diabetic (T2D) patients. FXR-mediated bile acid signaling has been reported to play key roles in improving metabolic parameters in vertical sleeve gastrectomy surgery, implying that FXR is an essential modulator in the metabolic homeostasis. Using a genetic mouse model, intestinal specific FXR-null mice have been reported to be resistant to diet-induced obesity and insulin resistance. Moreover, intestinal specific FXR agonism using gut-specific FXR synthetic agonist has been shown to enhance thermogenesis in brown adipose tissue and browning in white adipose tissue to increase energy expenditure, leading to reduced body weight gain and improved insulin resistance. Altogether, FXR is a potent therapeutic target for the treatment of metabolic diseases.

HOXC10 suppresses browning of white adipose tissues

Given that increased thermogenesis in white adipose tissue, also known as browning, promotes energy expenditure, significant efforts have been invested to determine the molecular factors involved in this process. Here we show that HOXC10, a homeobox domain-containing transcription factor expressed in subcutaneous white adipose tissue, is a suppressor of genes involved in browning white adipose tissue. Ectopic expression of HOXC10 in adipocytes suppresses brown fat genes, whereas the depletion of HOXC10 in adipocytes and myoblasts increases the expression of brown fat genes. The protein level of HOXC10 inversely correlates with brown fat genes in subcutaneous white adipose tissue of cold-exposed mice. Expression of HOXC10 in mice suppresses cold-induced browning in subcutaneous white adipose tissue and abolishes the beneficial effect of cold exposure on glucose clearance. HOXC10 exerts its effect, at least in part, by suppressing PRDM16 expression. The results support that HOXC10 is a key negative regulator of the process of browning in white adipose tissue.

Skeletal Muscle Thermogenesis and Its Role in Whole Body Energy Metabolism

Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis.

Thermographic analysis and autonomic response in the hands of patients with leprosy

Abstract: Background: Low temperatures and slow blood flow may result from peripheral neuropathy caused by leprosy, and the simple detection of cold fingers could already be a preliminary classification for these patients. Objective: To investigate whether infrared thermography would be able to measure this change in temperature in the hands of people with leprosy. Method: The study assessed 17 leprosy patients who were under treatment at the National Reference Center for Sanitary Dermatology and Leprosy, Uberlândia/MG, and 15 people without leprosy for the control group. The infrared camera FLIR A325 and Therma CAM Researcher Professional 2.9 software were used to measure the temperature. The room was air-conditioned, maintaining the temperature at 25°C; the distance between the camera and the limb was 70 cm. The vasomotor reflex of patients was tested by a cold stress on the palm. Results: The study showed a significant interaction between the clinical form of leprosy and temperature, where the control group and the borderline-borderline form revealed a higher initial temperature, while borderline-lepromatous and lepromatous leprosy showed a lower temperature. Regarding vasomotor reflex, lepromatous leprosy patients were unable to recover the initial temperature after cold stress, while those with the borderline-tuberculoid form not only recovered but exceeded the initial temperature. Conclusion: Thermography proved a potential tool to assist in the early detection of neuropathies, helping in the prevention of major nerve damage and the installation of deformities and disabilities that are characteristic of leprosy.

Food Intake and Thermogenesis in Adipose Tissue

Brown adipose tissue (BAT) is regarded as a key target for developing interventions to prevent and treat obesity and age-related diseases. In addition, uncoupling pro tein 1 (UCP1)

Eosinophils and Type 2 Cytokine Signaling in Macrophages Support the Biogenesis of Cold-induced Beige Fat

Brown adipose generates heat via oxidation of fatty acids by a mitochondrial uncoupling protein 1 (UCP1)-dependent process. In addition, a subpopulation of cells within subcutaneous white adipose tissue, known as beige adipocytes, also plays a role in thermogenesis. The biogenesis of beige adipocytes is induced by thermogenic signals, such as chronic cold exposure. Recently, it has been reported that eosinophils, type 2 cytokines of IL-4/13, and alternatively activated macrophages control the thermogenic cycle of beige adipocytes. Alternatively, activated macrophages induce UCP1+ beige adipocytes through secretion of catecholamines. These results define the role of type 2 immune responses in the regulation of energy homeostasis.

Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity

Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine that has various functions in both neuronal and non-neuronal systems. In the central nervous system, 5-HT regulates mood and feeding behaviors as a neurotransmitter. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. Unfortunately, some drugs were withdrawn due to the development of unwanted peripheral side effects, such as valvular heart disease and pulmonary hypertension. Recent studies revealed that peripheral 5-HT plays an important role in metabolic regulation in peripheral tissues, where it suppresses adaptive thermogenesis in brown adipose tissue. Inhibition of 5-HT synthesis reduced the weight gain and improved the metabolic dysfunction in a diet-induced obesity mouse model. Genome-wide association studies also revealed genetic associations between the serotonergic system and obesity. Several genetic polymorphisms in tryptophan hydroxylase and 5-HT receptors were shown to have strong associations with obesity. These results support the clinical significance of the peripheral serotonergic system as a therapeutic target for obesity and diabetes.

The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells

The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001). Moreover, FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006), hemoglobin levels (rs =0.210, P=0.049), and percentage of peripheral blood blasts (rs =0.256, P=0.027), but inversely correlated with hemoglobin levels in the control group (rs =–0.391, P<0.0001). AML patients with high CD34+ expression showed significantly higher FAMLF-CS expression than those with low CD34+ expression (P=0.041). Our results showed that FAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.

Endoscopic Dacryocystorhinostomy Using Ultrasonic Bone Aspirator

PURPOSE: To report the results of 15 endoscopic dacryocystorhinostomy (eDCR) cases using ultrasonic bone aspirator (UBA) and evaluate the UBA efficiency in these surgeries. METHODS: Fifteen eyes of 12 patients presenting with nasolacrimal duct obstruction were evaluated in the present study. eDCR and osteotomy were performed using UBA (Cusa excel, Integra, New Jersey, NJ, USA) from January 2014 to June 2014. RESULTS: All the patients showed complete resolution of the epiphora. There were no complications or recurrences for a minimum of 10 months postoperatively. CONCLUSIONS: This is the first report on eDCR using UBA. The surgeries were successful and no complications were observed. eDCR using UBA is an easy, safe and effective technique with minimal heat production, minimal damage to the surrounding soft tissue and quick and precise bone removal.