Effect of diet and physical exercise on weight, body composition, and resting metabolic rate in obese chilean adults

ABSTRACT Background: Diet and exercise are the mainstay of weight reduction programs. Aim: To evaluate the effect of diet and exercise on body weight and composition and resting metabolic rate (RMR) in obese adults. Material and Methods: Twenty-eight obese adults aged 22 to 61 years (18 women) completed four months of diet and exercise. They attended monthly nutritional consultations, and two-three weekly exercise sessions. At baseline and the end of the intervention, anthropometry, body composition by bioimpedance and RMR by indirect calorimetry (IC) were measured. Metabolic adaptation, defined as a decrease in thermogenesis to an extent greater than predicted based on the change in body weight and composition, was calculated. RESULTS: Significant reductions in body weight and fat mass were observed in both genders. Fat-free mass decreased in women and remained unchanged in men. RMR remained stable. Metabolic adaptation was observed in 11/27 participants. Fat mass change in participants with and without metabolic adaptation was 8 Kg and 4,4 kg, respectively (p = 0,018). In the linear regression analysis, male sex accounted for a higher RMR (247.80 Kcal, p = 0,006) than females. For each kg of fat and fat free mass, the RMR varies 7.25 Kcal, (p = 0.02) and 9.79 Kcal (p = 0,006), respectively. CONCLUSIONS: The intervention reduced body weight and fat mass and maintained RMR. Fat free mass decreased in women. Participants with metabolic adaptation showed greater changes in fat mass.

ANTECEDENTES: Para el tratamiento de la obesidad, la dieta y ejercicio físico (EF) contribuyen a reducir el peso corporal (PC), masa grasa (MG) y a mantener la masa libre de grasa (MLG) y tasa metabólica en reposo (TMR). Objetivo: Evaluar el efecto de la dieta y EF sobre el PC, composición corporal (CC), TMR y la presencia de adaptación metabólica. MATERIAL Y MÉTODOS: Veintiocho adultos obesos completaron cuatro meses de dieta y EF. Los adultos asistieron a consulta nutricional mensual y a 2-3 sesiones de EF semanal. En el período basal y después de la intervención se midió antropometría, CC por bioimpedanciometria y TMR por calorimetría indirecta. Se calculo la presencia de adaptación metabólica, definida como una disminución de la termogénesis mayor que la predicha por el cambio en peso y composición corporal. Resultados: Se observó una disminución significativa de PC y MG en hombres y mujeres. La MLG disminuyó en las mujeres y se mantuvo en los hombres. La TMR se mantuvo estable. Se observó adaptación metabólica en 11/27 participantes y una relación significativa con el cambio en MG (p = 0,018). En la regresión lineal, el sexo masculino da cuenta de una mayor TMR (247,80 Kcal, p = 0,006) que el sexo femenino. Por cada kg de MG y MLG la TMR varía 7,25 Kcal, (p = 0,02) y 9,79 Kcal, (p = 0,006) respectivamente. CONCLUSIONES: La intervención redujo el PC y la MG, y mantuvo TMR. La MLG disminuyó en las mujeres. Los sujetos con adaptación metabólica mostraron mayores cambios de MG.

Fructose consumption induces molecular adaptations involving thyroid function and thyroid-related genes in brown adipose tissue in rats

The increasing incidence of metabolic diseases is in part due to the high fructose consumption, a carbohydrate vastly used in industry, with a potent lipogenic capacity. Thyroid hormones (TH) are essential for metabolism regulation and are associated with changes in body weight, energy expenditure, insulin sensitivity, and dyslipidemia. This study aimed to investigate the influence of fructose intake on thyroid function and thyroid-related genes. Male Wistar rats were divided into Control (CT, n=8) and Fructose (FT - 10% in drinking water, n=8) groups for three weeks. The FT group showed higher glycemia and serum triacylglycerol, indicating metabolic disturbances, and increased thyroid mass, accompanied by higher expression of Srebf1c and Lpl, suggesting increased lipid synthesis. The FT group also presented higher expression of Tpo and Dio1 in the thyroid, suggesting activation of the thyroid gland, but with no alterations in serum TH concentrations. Brown adipose tissue (BAT) of the FT group exhibited higher expression of Dio2, Thra, and Thrb, indicating increased T3 intra-tissue bioavailability and signaling. These responses were accompanied by increased BAT mass and higher expression of Adrb3, Pparg, Srebf1c, Fasn, Ppara, and Ucp1, suggesting increased BAT adrenergic sensitivity, lipid synthesis, oxidation, and thermogenesis. Therefore, short-term fructose consumption induced thyroid molecular alterations and increased BAT expression of thyroid hormone-related signaling genes that potentially contributed to higher BAT activity.

Effects of N-Oleoylglycine and Oleate on Mitochondrial UCP1-independent Thermogenesis / 中国生物化学与分子生物学报

Besides UCP1-dependent thermogenesis pathways, UCP1-independent thermogenesis pathways also could increase heat production in adipose tissue to combat obesity. N-Acyl amino acids (NAAs) have been suggested as novel endogenous uncouplers to induce mitochondria UCP1-independent thermogenesis in adipose tissue. Here, we use mouse skeletal muscle C2C12 cells which lack of UCP1 as UCP1 negative cell models. Comparing with its corresponding common fatty acid—oleate, one of the NAAs—N-Oleoylglycine (NOGly), which is highly expressed in the plasma of HFD mice, is selected to study their effects and mechanisms on mitochondrial thermogenesis. We found that 60 μmol / L oleate could induce mitochondrial oxidative phosphorylation protein levels, as well as increase mitochondria thermogenesis-related genes (COX8b, DIO2, UCP3) expression (P < 0. 05) . However, 60 μmol / L NOGly damaged the production and oxidative phosphorylation of mitochondria, significantly down-regulated expression of thermogenic genes (PGC1a, COX8b, COX2, DIO2, UQCRFS1and UCP3) (P< 0. 01), induced the production of reactive oxygen species (ROS) in the mitochondria, and enhanced the oxidative stress in cells. Our study found that oleate can induce UCP1-independent thermogenesis under 60 μmol / L addition dose, whereas NOGly does not due to the induction of oxidative stress in cells.

Rnf20 deficiency in adipocyte impairs adipose tissue development and thermogenesis

RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

Higher increase degree of FGF21 post long-term interdisciplinary weight loss therapy preserves the free fat mass and rest metabolic rate in adolescents with obesity

ABSTRACT Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.

Duodenal-jejunal bypass reduces lipid accumulation in the brown adipose tissue of hypothalamic obese rats / Derivação duodeno-jejunal reduz o acúmulo de lipídios no tecido adiposo marrom de ratos com obesidade hipotalâmica

ABSTRACT Background: Thermogenic activity in the brown adipose tissue (BAT) of obese individuals is reduced, and this condition may be modified by bariatric surgery (BS). Aim: To characterize fat deposition in BAT from hypothalamic obese (HyO) rats submitted to duodenal-jejunal-bypass (DJB) surgery. Methods: For induction of hypothalamic obesity, newborn male Wistar rats were treated with subcutaneous injections of monosodium glutamate (MSG). The control (CTL) group received saline solution. At 90 days, the HyO rats were submitted to DJB or sham operation, generating the HyO-DJB and HyO-SHAM groups. At 270 days, the rats were euthanized, and the BAT was weighed and submitted to histological analysis. Results: Compared to BAT from CTL animals, the BAT from HyO-SHAM rats displayed increased weight, hypertrophy with greater lipid accumulation and a reduction in nucleus number. DJB effectively increased nucleus number and normalized lipid deposition in the BAT of HyO-SHAM rats, similar to that observed in CTL animals. Conclusion: DJB surgery avoided excessive lipid deposition in the BAT of hypothalamic obese rats, suggesting that this procedure could reactivate thermogenesis in BAT, and contribute to increase energy expenditure.

RESUMO Racional: A atividade termogênica no tecido adiposo marrom (TAM) de indivíduos obesos encontra-se reduzida, condição que pode ser modificada pela cirurgia bariátrica(CB). Objetivo: Verificar o efeito da derivação duodeno-jejunal (DDJ) sobre a morfologia do TAM de ratos com obesidade hipotalâmica. Métodos: Para indução da obesidade hipotalâmica (OHi), ratos Wistar neonatos receberam injeções subcutâneas de glutamato monossódico (MSG). O grupo controle (CTL) recebeu solução salina. Aos 90 dias, os ratos OHi foram submetidos à DDJ (grupo OHi-DDJ) ou a falsa operação (grupo OHi-FO). Aos 270 dias, eles foram eutanasiados e o TAM foi pesado e submetido à análise histológica. Resultados: Em comparação com os animais CTL, o TAM dos ratos OHi-FO apresentou aumento do peso, hipertrofia dos adipócitos com acúmulo de lipídios e redução do número de núcleos. A DDJ reduziu a deposição de gordura e o número de núcleos no TAM de ratos OHi-DDJ em comparação com os OHi-FO, com valores similares aqueles dos animais CTL. Conclusões: A DDJ foi capaz de evitar a deposição excessiva de lipídios no TAM de ratos com obesidade hipotalâmica, sugerindo que a cirurgia bariátrica poderia reativar a termogênese neste tecido adiposo, contribuindo para aumentar o gasto energético.

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.

Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase (AMPK)-dependent pathway

Obesity is a worldwide epidemic. Promoting browning of white adipose tissue (WAT) contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin (Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1 (UCP1) and other thermogenic genes in WAT and 3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase (AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.

Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats.@*METHODS@#In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw).@*RESULTS@#In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity.@*CONCLUSION@#These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.

Efecto de ingesta de calcio del desayuno en la termogénesis alimentaria y oxidación de grasas postprandial en mujeres con sobrepeso / Effect of Breakfast Calcium Intake on Food Thermogenesis and Posprandial Fat Oxidation in Overweight Women

Resumen Antecedentes: una alta ingesta de calcio se relaciona con mayor termogénesis alimentaria y oxidación de grasa posprandial. Objetivo: evaluar el efecto de la ingesta de calcio del desayuno con termogénesis alimentaria y oxidación de grasas posprandial, en mujeres con sobrepeso. Materiales y métodos: estudio experimental, aleatorizado, conformado por 16 mujeres (ocho en el grupo experimental y ocho en el grupo control) entre 20-25 años. Se evaluó IMC, composición corporal mediante bioimpedanciometría, tasa metabólica en reposo en ayuno y posprandial mediante calorimetría indirecta, oxidación de grasa mediante cociente respiratorio y vitamina D sérica por radioinmunoensayo. Se administró al azar un desayuno isocalórico (377 kcal), alto en calcio (625 mg) o habitual en calcio (306 mg). Se describió con mediana y percentiles, y se comparó con pruebas Mann-Whitney y Wilcoxon para muestras pareadas. Resultados: la mediana de masa grasa y masa libre de grasa fue 30,9 % (27,5-33,9); 69,1 % (66,2-72,5) en el grupo experimental y 32,2 % (30,1-34,7); 67,8 % (65,3-69,9) en el grupo control (p=0,372). El grupo experimental mostró un aumento estadísticamente significativo en la termogénesis posprandial después del desayuno (p=0,035). Ambos grupos mostraron una mediana en cociente respiratorio posprandial aproximado a 1, (p=0,207), oxidando preferentemente carbohidratos. Conclusiones: las mujeres con desayuno alto en calcio presentan posterior al desayuno mayor termogénesis alimentaria, pero no mayor oxidación de grasa posprandial.

Abstract Background: High calcium intake is related to higher food thermogenesis and posprandial fat oxidation. Objective: Evaluate the calcium intake level at breakfast and both food thermogenesis and posprandial fat oxidation in overweight women. Materials and Methods: Experimental study with a random sample of 16 women, experimental group (8) and control group (8) aged 20-25 years. BMI, body composition by bioimpedance, resting metabolic rate at fasting, and posprandial were evaluated by indirect calorimetry; fat oxidation by respiratory quotient; and serum vitamin D by radioimmunoassay. Two types of isocaloric (377 kcal) breakfasts that were high (625 mg) or habitual (306 mg) in calcium were randomly administered. Results were described by medians and percentiles, which were compared by the Mann-Whitney test and Wilcoxon matched-paired test. Results: Median fat mass and fat-free mass was 30.9 % (27.5-33.9) and 69.1 % (66.2-72.5), and 32.2 % (30.1-34.7) and 67.8% (65.3-69.9) in the experimental and control group, respectively (p=0.372). The experimental group exhibited a statistically significant increase in posprandial breakfast thermogenesis (p=0.035). Both groups showed an approximate posprandial RQ median of 1 (p=0.207); they tended to oxidize carbohydrates. Conclusions: Women who consumed a high calcium breakfast exhibited higher post-breakfast food thermogenesis, but posprandial fat oxidation was not higher.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy / Eficácia da hipotermia passiva e eventos adversos durante o transporte de recém-nascidos asfixiados de acordo com a gravidade da encefalopatia hipóxico-isquêmica

Abstract Objective To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and <33 °C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature < 33 °C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p < 0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. Conclusion The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport.

Resumo Objetivo Determinar se a eficácia da hipotermia passiva e eventos adversos durante o transporte estão relacionados à gravidade da encefalopatia hipóxico-isquêmica neonatal. Métodos Estudo retrospectivo de 67 neonatos com encefalopatia hipóxico-isquêmica (nascidos entre abril de 2009 e dezembro de 2013) transferidos para hipotermia terapêutica e resfriados durante o transporte. Resultados Foram transportados 56 recém-nascidos (84%) sem fontes externas de calor e 11 (16%) precisaram de uma fonte externa de calor. A temperatura média na saída foi de 34,4 ± 1,4 °C e o tempo médio de transporte foi de 3,3 ± 2,0 horas. A idade média na chegada foi de 5,6 ± 2,5 horas. A temperatura na chegada ficou entre 33-35 °C em 41 (61%) neonatos, entre 35°-36,5 °C em 15 (22%) e < 33 °C em 11 (16%). Neonatos com encefalopatia hipóxico-isquêmica grave apresentaram maior risco de temperatura < 33 °C na internação (RC 4,5; IC de 95% 1,1-19,3). A gravidade da encefalopatia hipóxico-isquêmica e o pH da artéria umbilical foram fatores de risco independentes para uma baixa temperatura na internação (p < 0,05). Eventos adversos durante o transporte, principalmente hipotensão e sangramento do tubo endotraqueal, ocorreram em 14 neonatos (21%), sem diferenças entre neonatos com encefalopatia hipóxico-isquêmica moderada ou grave. Conclusão O risco de super-resfriamento durante o transporte é maior em recém-nascidos com encefalopatia hipóxico-isquêmica grave e naqueles com acidose mais grave no nascimento. Os eventos adversos mais comuns durante o transporte estão relacionados a deterioração fisiológica e sangramento do tubo endotraqueal. Essa observação fornece informações úteis para identificar neonatos asfixiados que exigem maior vigilância clínica durante o transporte.

The dark side of browning

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.

Brown adipose tissue thermogenesis and energy metabolism / 体力科学

Obesity and diabetes have become a major epidemic problem. Preventing obesity has proven a challenge because this would require increased physical activity and/or reduced energy intake; both of which are difficult to enforce. Brown adipose tissue (BAT) is a major metabolic organ that contributes to the regulation of energy metabolism in small rodents. In humans, since its rediscovery in 2009, BAT has emerged as a potential target to fight obesity and related metabolic diseases such as type 2 diabetes. The BAT of humans is activated by acute cold exposure and mediates cold-induced thermogenesis. The metabolic activity of BAT demonstrates huge individual variation and is negatively associated with body fat accumulation and glucose intolerance. The decreased BAT can be reactivated and recruited by repeated cold exposure, which has the effects of increasing thermogenesis and decreasing body fat. Such effects of cold exposure can be mimicked by oral ingestion of some food ingredients with agonistic activity at temperature-sensitive transient receptor potential channels. To develop strategies to boost BAT thermogenesis for obesity prevention, more insight is needed into the physiological significance of human BAT and mechanisms by which BAT function is regulated by aging, as well as endogenous and environmental factors. This review will summarize the current knowledge on the activation of human BAT thermogenesis and its roles in obesity-related disorders.

Energy balance and its components: implications of intra- and inter-individual variation on energy intake and expenditure / 体力科学

Energy balance in human body undergoes constant change, leading to a change in the weight and body composition throughout life. Energy balance at a particular time point is influenced by the psychological, physiological, sociological, and environmental factors of that moment. In addition, the regulation of homeostasis continuously monitors and maintains the energy balance; however, it complicates the identification of factors influencing the energy balance. For understanding these factors, creating a model with comprehensive factors and testing it among a substantial number of individuals for dynamic changes in the energy balance may be warranted. However, till date, to the best of our knowledge, no studies report on comprehensive modeling, including homeostasis and the other factors. Thus, at this moment, summarizing previous studies for further research is required. Accordingly, this review summarizes 1) the basic factor of energy expenditure and intake; 2) interactive relationship between energy expenditure and intake; and 3) energy expenditure and intake during dynamic changes in the body weight caused by events such as overfeeding, underfeeding, growth and aging, and pregnancy.

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.

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.

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.

Effects of eating speed on diet-induced thermogenesis / 体力科学

Overweight or obesity becomes a worldwide public health issue; the global obesity pandemic. Strategies to effectively prevent overweight and obesity are needed. Slow eating, which involves chewing food slowly and thoroughly, can be an effective strategy to prevent overweight and obesity. Previous studies reported a relationship between rapid eating and overweight. Candidate factors inducing the relationship have been thought to be related to increases in appetite and energy intake through rapid eating, allowing the ingestion of a greater-than-optimal volume of food. While the counter effect of slow eating has been widely known, effects of eating speed on digestion, absorption, and metabolism has yet to be elucidated. If eating speed affects digestion, absorption, and metabolism, eating speed can be a factor explaining the relationship between eating speed and body composition. The present review is to summarize the effects of eating speed on digestion, absorption, and metabolism, consequently suggesting preferable effects of slowly eating on increasing energy expenditure after eating.

Peroxisome proliferator-activated receptor γ and regulation of adaptive thermogenesis / 国际药学研究杂志

Adaptive thermogenesis is an important manner to keep homeostasis of energy metabolism by non-shivering thermogenesis(NS). In addition to brown adipose tissue, the beige adipose tissue induced by cold stimulation in subcutaneous white adipose tissue (WAT) also proceeds NS in mice. Regulating NS to increase excess energy expense of the body may be a safe and effective method for the treatment of obesity, insulin resistance and the disorder of energy metabolism. Peroxisome proliferator-activated receptor γ(PPARγ) is an important transcription factor whose activator can induce the production of adipose tissue cell in pharmacological doses. This paper reviewes the function of PPARγ in adaptive thermogenesis and analyzes the possible mechanism of selective modulation of PPARγ. It may become the theoretical basis of a new generation of insulin sensitizing agent.

Adaptive thermogenesis of the brown adipose tissue in tree shrews (Tupaia belangeri) during cold acclimation / 中国实验动物学报

Objective To investigate the effect of ambient temperature on body mass, thermogenic activity and un-coupling protein-1 ( UCP1) content of brown adipose tissue ( BAT) in tree shrews ( Tupaia belangeri) , and to provide the-oretical basis for establishing tree shrews model of obesity.Methods Forty healthy adult tree shrews with similar body mass were uesd in our experiment.The tree shrews were divided into five groups (n=8):control group (0 d), the ani-mals were maintained under 25 ±1℃ and 12L:12D ( light : dark, lights on 08:00) photoperiod; and the animals were maintained under 5 ±1℃and 12L:12D photoperiod for 7 d, 14 d, 21 d and 28 d groups, respectively.At the end of ex-periment, the changes of body mass, nonshivering thermogenesis (NST), BAT mass and uncoupling protein 1 (UCP1) con-tent were determined.Results Compared with the control group (0 d), the body mass, NST, BAT mass and UCP1 con-tent of the cold acclimation groups were improved significantly, the BAT color also obviously deepened, and after cold accli-mation for 28 d, the body mass, NST, BAT mass and UCP1 content were increased by 26.32%, 20.65, 53.85%and 43%, respectively.Apparently, the UCP1 content was significantly positively correlated with BAT mass and NST.Conclusions BAT proliferation may be induced and UCP1 expression upregulated by cold acclimation in Tupaia belangeri, therefore, en-hancing the thermogenic activity of brown adipose tissue to increase energy expenditure.We would speculate that BAT might be used as a target organ for treatment of obesity by energetic approach in the future.