Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

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.

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.

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.

Brown adipose tissue: what have we learned since its recent identification in human adults / Tecido adiposo marrom: o que aprendemos desde sua recente identificação em humanos adultos

Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis. Arq Bras Endocrinol Metab. 2014;58(9):889-99.

O tecido adiposo marrom, órgão essencial para a termorregulação de animais hibernantes e pequenos devido à sua capacidade desacopladora, era até poucos anos considerado presente apenas em recém-nascidos na espécie humana. A identificação do tecido adiposo marrom em adultos com o desenvolvimento e uso da tomografia de emissão de pósitron marcado com 18-fluorodesoxiglicose (PET-FDG) gerou questões sobre sua real importância para nosso metabolismo. Nesta revisão, discutiremos o que aprendemos nesse tempo, assim como conceitos antigos e novos, alguns marginalizados por décadas, como a termogênese induzida por dieta. Arq Bras Endocrinol Metab. 2014;58(9):889-99.

Grasa parda / Postgraduate medical specialties

La obesidad ha alcanzado proporciones epidèmicas, las complicaciones relacionadas con ella contribuyen sustancialmente al costo de salud.

Funciona el tejido adiposo marrón como un depósito de acidos grasos poliinsaturados de cadena larga durante el desarrollo postnatal del cerebro? / [Is brown adipose tissue a store of long chain polyunsaturated fatty acids during postnatal developing brain?]

Mammals along their early postnatal period develop a substantial amount of a very active brown adipose tissue (BAT). Through this work we explored the possibility that BAT may function as a long chain polyunsaturated fatty acids reservoir (LC-PUFA) during the rapid growth of brain structures. In new born rats 1, 6, 12 and 20 days old, we analyzed fatty acid percentage of triglycerides (TG) and phospholipid fractions, and the absolute amount of TG. In 6 day old rats we also evaluated the extend of further desaturation of 1-14C linoleic acid administered by intraperitoneal injection. Results demonstrated a drastic increase of TG concentration during experimental period (1,5; 40; 118; 120 mg/g wet weight) and LC-PUFA percentage was higher in [quot ]1 and 6[quot ] than [quot ]12 and 20[quot ] days old rats (16-17% vs 5%). Our results showed that BAT stored important amounts of LC-PUFA. On the other hand, 1-14C linoleic acid incorporation was higher in liver than BAT. In contrast, the desaturated products of 1-14C linoleic acid /1-14C linoleic acid ratio was greater in BAT than liver (>4). This could indicate that BAT synthesizes LC-PUFA in addition to store it. In summary we demonstrated than BAT is an important reservoir of LC-PUFA during postnatal brain growth.

Los mamíferos como el hombre y la rata, poseen durante su desarrollo postnatal temprano un tejido adiposo marrón (TAM) muy activo. En este trabajo se exploró la posibilidad de que el TAM funcione como un depósito de ácidos grasos poliinsaturados de cadena larga (AGPI-CL), durante el período de máximo crecimiento postnatal del cerebro de rata. En el TAM de ratas de 1, 6, 12 y 20 días de edad analizamos la concentración de triglicéridos (TG) y la composición de ácidos grasos en los TG y fosfolípidos (FL). Además, en ratas de 6 días de edad evaluamos la capacidad del TAM para desaturar 1- 14C ácido linoleico administrado por vía intraperitoneal. Los resultados mostraron un rápido incremento en la concentración de TG durante el período experimental (1,5; 40; 118; 120 mg /g de peso húmedo). El porcentaje de AGPI-CL fue mayor en las ratas de 1 y 6 días de edad que en las de 12 y 20 días (16-17% vs 5%). Por otra parte, la incorporación de 1-14C ácido linoleico fue más alta en el hígado que en el TAM, aunque la relación "productos desaturados de 1-14C ácido linoleico / 1-14C ácido linoleico" fue mayor en el TAM que en el hígado (>4), lo cual podría indicar que este tejido además de almacenar AGPI-CL los sintetiza. En resumen, nuestros resultados demuestran que el TAM es depósito importante de AGPICL durante el período de máximo desarrollo postnatal del cerebro.

Mielolipoma gigante: relato de caso e revisão da literatura / Giant myelolipoma: case report and review of the literature

Mielolipomas são tumores benignos raros compostos por tecido adiposo maduro e por elementos hematopoiéticos. Geralmente são menores que 5 cm e assintomáticos, embora lesões maiores podem apresentar-se com dor ou hemorragia retroperitoneal. Descrevemos um caso de mielolipoma gigante, associado à hemorragia retroperitoneal após biópsia por punção com agulha fina

O teor de sódio da dieta modula a expressão gênica dor transportadores de glicose em diferentes territórios do organismo / Dietary sodium modulates glucose transporters gene expression in different territories of organism

Verificamos o efeito do teor de sódio da dieta sobre a expressão gênica dos transportadores de glicose em tecido adiposo branco e marrom, muscular esquelético e cardíaco, intestino e rim de ratos tratados cronicamente com dietas normossódica (NS), hipossódica (LS) e hipersódica (HS).Em HS, aumento da sensibilidade insulínica se relacionou com aumentada expressão do gene do GLUT4 e translocação da sua proteína. Por outro lado, modulações na expressão gênica dos transportadores de glicose em intestino (SGLT1 e GLUT2) e rim (SGLT2, GLUT2 e GLUT1) foram observadas em HS e LS, mas não repercutiram em alterações de absorção intestinal e reabsorção renal de glicose.In the present study we verified the effect of dietary sodium content on the glucose transporters gene expression in white and brown adipose tissues, skeletal and cardiac muscles, intestine and kidney of chronically treated rats with normal- (NS), low- (LS) or hig- (HS) sodium diets. HS-treated rats showed higher insulin sensitivity, which was related to increased GLUT4 gene expression in insulin sensitive tissues, as well, to increased protein translocation. However, the modulations of HS and LS on intestinal (SGLT1 and GLUT2) and renal (SGLT2, GLUT2 and GLUT1) glucose transporters expressions did not reflect on intestinal absorption and renal reabsorption of glucose...

Changes in thyroid hormone and insulin status of the brown adipose tissue of cold acclimated rats on short term exposure to heat.

Acclimation of rats to cold caused 45% increase in the concentration of triidothyronine (T3) and 35% increase in the concentration of thyroxine (T4) in serum. Exposure of cold-acclimated rats to heat (12 hr, 37 degrees C) failed to decrease the concentrations of thyroid hormones in circulation. The concentration of T3 in brown adipose tissue (BAT) increased almost 10-fold on cold acclimation. Iodothyronine deiodinase activity also registered 3-fold increase. Exposure of cold-acclimated animals to heat caused decrease in the concentration of T3 in BAT without appreciably affecting T4 concentration. In liver tissue, the changes in hormone concentrations were quite small compared to those in BAT. On thyroidectomy or when fed with propyl thiouracil, rats could not survive exposure to the cold. The concentration of insulin in circulation showed small increase, while that in the tissues showed significant decrease on acclimation of rats to the cold. The concentration of the hormone in BAT registered significant increase on exposure of cold-acclimated animals to heat (12 hr, 37 degrees C). The increase in liver was marginal. The temperature-dependent response of T3 indicates an important role for this hormone in rapid physiological response in BAT.