Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functi...Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functioning as symbionts within the host,possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host.This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures,as well as the underlying mechanism involving the"gut-brain"axis.Methods Broilers were subjected to gut microbiota interference with or without antibiotics(control or ABX)starting at 1 day of age.At 21 day of age,they were divided into 4 groups and exposed to different environments for 7 d:The control and ABX groups at room temperature(RT,24±1℃,60%relative humidity(RH),24 h/d)and the control-HT and ABX-HT groups at high temperature(HT,32±1℃,60%RH,24 h/d).Results The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens(P<0.05).Under HT conditions,the microbiota intervention reduced the rectal temperature of broiler chickens(P<0.05),inhibited the expression of avUCP and thermogenesisrelated genes in breast muscle and liver(P<0.05),and thus decreased thermogenesis capacity.Furthermore,the gut microbiota intervention blunted the hypothalamic‒pituitary‒adrenal axis and hypothalamic–pituitary–thyroid axis activation induced by HT conditions.By analyzing the cecal microbiota composition of control and ABX chickens maintained under HT conditions,we found that Alistipes was enriched in control chickens.In contrast,antibioticinduced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes(P<0.05).Moreover,this difference was accompanied by increased hypothalamic 5-hydroxytryptamine(5-HT)content and TPH2 expression(P<0.05).Conclusions These findings underscore the critical role of the gut microbiota in regulating broiler thermogenesis via the gut-brain axis and suggest that the hypothalamic 5-HT pathway may be a potential mechanism by which the gut microbiota affects thermoregulation in broilers.展开更多
Purpose: Frailty is a state of declined vitality of the body and mind with age in which life functions are impaired. In addition, there is a difference in the susceptibility of older women to frailty compared with tha...Purpose: Frailty is a state of declined vitality of the body and mind with age in which life functions are impaired. In addition, there is a difference in the susceptibility of older women to frailty compared with that of older men. Therefore, assessing and encouraging physical activity in older adults before they become frail is essential. We aimed to clarify the relationship between calf circumference and body composition and assess the potential association between calf circumference and physical activity indices in older women. Methods: This cross-sectional study included 18 healthy older adults (age 69.0 ± 5.7 years). The physical characteristics, calf circumference, body composition, calf muscle thickness, and physical activity questionnaire that included items on exercise-related activity thermogenesis (EAT) and nonexercise activity thermogenesis (NEAT) were assessed. The association between calf circumference and these additional measures was examined. Results: Positive and significant correlations were found between the calf circumference and body weight, body mass index (BMI), skeletal muscle mass, skeletal muscle mass index, calf muscle thickness, total questionnaire score, and NEAT score (r = 0.66 - 0.87). However, no significant correlations were observed between the calf circumference and EAT scores. Conclusion: Calf circumference in older women may reflect NEAT activity. Improving NEAT activity is an important health-promoting factor in older women.展开更多
Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed tha...Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.展开更多
An immense amount of information has now accrued about the factors that influence the increment of heat and the efficiency with which the energy of food is used by different animal species. Heat increment is one of th...An immense amount of information has now accrued about the factors that influence the increment of heat and the efficiency with which the energy of food is used by different animal species. Heat increment is one of the major factors that decrease the efficiency of energy utilization. In growing animals, the free energy content of the basal ATP requirement is typically about one-third of dietary basal heat production （thermogenesis）. Thermogenesis is an evolutionary and biologically significant mechanism for adaptive, homeostatic heat production in animals, including shivering thermogenesis （ST）, nonshivering thermogenesis （NST）, diet-induced thermogenesis （DIT）, febrile response （fever）, and so on. The main focus of this review is on the effect of DIT on energy metabolism.展开更多
Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all physical activities other than volitional sporting-like exercise. NEAT includes all the activities that render us vibrant, unique and indepen...Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all physical activities other than volitional sporting-like exercise. NEAT includes all the activities that render us vibrant, unique and independent beings such as working, playing, and dancing. Because people of the same weight have markedly variable activity levels, it is not surprising that NEAT varies substantially between people by 2000 kcal/day. Evidence suggests that low NEAT may occur in obesity but in a very specific fashion. Obese individuals appear to exhibit an innate tendency to be seated for 2.5 hours per day more than sedentary lean counterparts. If obese individuals were to adopt the lean ‘NEAT-o-type’, they could potentially expend an additional 350 kcal/day. Obesity was rare a century ago and the human genotype has not changed over that time. Thus, the obesity epidemic may reflect the emergence of a chair-enticing environment to which those with an innate tendency to sit, did so and became obese. To reverse obesity therefore, we need to develop individual strategies to promote standing & ambulating time by 2.5 hours per day but also re-engineer our work, school and home environments to render active living the option of choice.展开更多
Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we sh...Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we show that a specific orexin receptor type 2(OX2R)agonist[Ala11,D-Leu15]-OxB(OB-Ala)inhibited intrascapular brown adipose tissue(iBAT)thermogenesis by reducing sympathetic output to iBAT.This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself.Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus.Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop.Our study uncovers a novel primary action site of orexin in the regulation of energy balance.展开更多
Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strateg...Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.展开更多
Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of br...Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in mice.However,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical modality.This study aimed at identifying a potential GPCR target to induce beige fat.We found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers.Inversely,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers.Moreover,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway.We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1.In conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.展开更多
基金the National Natural Science Foundation of China,grant numbers 32372935,32072781.
文摘Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functioning as symbionts within the host,possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host.This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures,as well as the underlying mechanism involving the"gut-brain"axis.Methods Broilers were subjected to gut microbiota interference with or without antibiotics(control or ABX)starting at 1 day of age.At 21 day of age,they were divided into 4 groups and exposed to different environments for 7 d:The control and ABX groups at room temperature(RT,24±1℃,60%relative humidity(RH),24 h/d)and the control-HT and ABX-HT groups at high temperature(HT,32±1℃,60%RH,24 h/d).Results The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens(P<0.05).Under HT conditions,the microbiota intervention reduced the rectal temperature of broiler chickens(P<0.05),inhibited the expression of avUCP and thermogenesisrelated genes in breast muscle and liver(P<0.05),and thus decreased thermogenesis capacity.Furthermore,the gut microbiota intervention blunted the hypothalamic‒pituitary‒adrenal axis and hypothalamic–pituitary–thyroid axis activation induced by HT conditions.By analyzing the cecal microbiota composition of control and ABX chickens maintained under HT conditions,we found that Alistipes was enriched in control chickens.In contrast,antibioticinduced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes(P<0.05).Moreover,this difference was accompanied by increased hypothalamic 5-hydroxytryptamine(5-HT)content and TPH2 expression(P<0.05).Conclusions These findings underscore the critical role of the gut microbiota in regulating broiler thermogenesis via the gut-brain axis and suggest that the hypothalamic 5-HT pathway may be a potential mechanism by which the gut microbiota affects thermoregulation in broilers.
文摘Purpose: Frailty is a state of declined vitality of the body and mind with age in which life functions are impaired. In addition, there is a difference in the susceptibility of older women to frailty compared with that of older men. Therefore, assessing and encouraging physical activity in older adults before they become frail is essential. We aimed to clarify the relationship between calf circumference and body composition and assess the potential association between calf circumference and physical activity indices in older women. Methods: This cross-sectional study included 18 healthy older adults (age 69.0 ± 5.7 years). The physical characteristics, calf circumference, body composition, calf muscle thickness, and physical activity questionnaire that included items on exercise-related activity thermogenesis (EAT) and nonexercise activity thermogenesis (NEAT) were assessed. The association between calf circumference and these additional measures was examined. Results: Positive and significant correlations were found between the calf circumference and body weight, body mass index (BMI), skeletal muscle mass, skeletal muscle mass index, calf muscle thickness, total questionnaire score, and NEAT score (r = 0.66 - 0.87). However, no significant correlations were observed between the calf circumference and EAT scores. Conclusion: Calf circumference in older women may reflect NEAT activity. Improving NEAT activity is an important health-promoting factor in older women.
文摘Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.
基金the projects of the Natural Science Foundation of Yunnan Province (2003C0048M,2006C0033Q)the 973 Prophase Project of China (2007CB116201-3)
文摘An immense amount of information has now accrued about the factors that influence the increment of heat and the efficiency with which the energy of food is used by different animal species. Heat increment is one of the major factors that decrease the efficiency of energy utilization. In growing animals, the free energy content of the basal ATP requirement is typically about one-third of dietary basal heat production （thermogenesis）. Thermogenesis is an evolutionary and biologically significant mechanism for adaptive, homeostatic heat production in animals, including shivering thermogenesis （ST）, nonshivering thermogenesis （NST）, diet-induced thermogenesis （DIT）, febrile response （fever）, and so on. The main focus of this review is on the effect of DIT on energy metabolism.
文摘Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all physical activities other than volitional sporting-like exercise. NEAT includes all the activities that render us vibrant, unique and independent beings such as working, playing, and dancing. Because people of the same weight have markedly variable activity levels, it is not surprising that NEAT varies substantially between people by 2000 kcal/day. Evidence suggests that low NEAT may occur in obesity but in a very specific fashion. Obese individuals appear to exhibit an innate tendency to be seated for 2.5 hours per day more than sedentary lean counterparts. If obese individuals were to adopt the lean ‘NEAT-o-type’, they could potentially expend an additional 350 kcal/day. Obesity was rare a century ago and the human genotype has not changed over that time. Thus, the obesity epidemic may reflect the emergence of a chair-enticing environment to which those with an innate tendency to sit, did so and became obese. To reverse obesity therefore, we need to develop individual strategies to promote standing & ambulating time by 2.5 hours per day but also re-engineer our work, school and home environments to render active living the option of choice.
基金supported by grants from the National Natural Science Foundation of China (Grants No. 31800971 and 81873654)
文摘Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we show that a specific orexin receptor type 2(OX2R)agonist[Ala11,D-Leu15]-OxB(OB-Ala)inhibited intrascapular brown adipose tissue(iBAT)thermogenesis by reducing sympathetic output to iBAT.This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself.Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus.Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop.Our study uncovers a novel primary action site of orexin in the regulation of energy balance.
基金funded by National Natural Science Foundation of China(NSFC 82070877)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-JB-010,2021-I2M-1-005)The National High Technology Research and Development Program of China(2017YFE0112900).
文摘Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.
基金funded by the National Natural Science Foundation of China(81570764)Guangzhou Science and Technology Project(201807010069)+2 种基金Shenzhen Science and Technology Project(JCYJ20190807154205627)Guangdong Natural Science Fund(2020A1515010365)Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population(2018B030322003KF01)received by Zhonghan Yang。
文摘Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in mice.However,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical modality.This study aimed at identifying a potential GPCR target to induce beige fat.We found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers.Inversely,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers.Moreover,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway.We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1.In conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.
基金内蒙古自治区重点研发和成果转化计划国际科技合作项目“引进肉羊运输福利标准成果示范项目(项目编号:2022YFYZ0001)”澳大利亚昆士兰大学资助的动物福利国际合作项目“Evaluation and Improvement of Sheep Welfare duringDaily Feeding Management and Transport in Cold Weather in InnerMongolia”农业重大技术协同推广项目“绒山羊提质增效关键技术集成推广与创新应用项目”。
