Obesity, which underlies various metabolic and cardio- vascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing ne...Obesity, which underlies various metabolic and cardio- vascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissi- pation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and dis- cuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better under- standing of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limi- tations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.展开更多
目的探讨缺血后处理对大鼠肝大部切除合并缺血再灌注损伤后残肝再生的影响。方法健康清洁级雄性SD大鼠90只,体质量230-280g。按随机数字表法将其随机分为单纯肝切除组(SH)、缺血再灌注组(IR)、后处理组(IPO)。各组大鼠肝左、中...目的探讨缺血后处理对大鼠肝大部切除合并缺血再灌注损伤后残肝再生的影响。方法健康清洁级雄性SD大鼠90只,体质量230-280g。按随机数字表法将其随机分为单纯肝切除组(SH)、缺血再灌注组(IR)、后处理组(IPO)。各组大鼠肝左、中叶切除,残肝(右、尾叶)做不同处理:SH组不阻断其血流,IR组阻断血流30min后恢复灌注,IPO组阻断血流30min,并于恢复灌注前进行30-30s循环3次IPO。术后1、6、12、24、48h取各组大鼠下腔静脉血及残肝组织,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、HGF、残肝组织PCNA阳性细胞比率和ATP、ADP、AMP含量,并计算残肝再生度。结果(1)IPO组1-48h各时点ALT、AST活性分别是(138±20)、(340±22)、(770±55)、(389±60)、(113±25)U/L和(247±31)、(509±51)、(972±77)、(955±159)、(222±44)U/L,明显低于IR组相应时点的ALT、AST活性,分别为(2944±37)、(560±69)、(1222±162)、(540±40)、(161±15)U/L和(439±34)、(669±94)、(1347±118)、(1274±223)、(403.4±68)U/L(均P〈0.05);(2)IPO组24、48h肝再生度(18.8%4-3.2%、34.0%4±3.5%)和PCNA阳性细胞比率(43.9%±2.7%、56.2%±4.0%)分别高于IR组的(11.3%.4±2.9%、26.8%±2.5%)和(34.5%4-2.8%、48.8%.4±1.8%)(P〈0.05);(3)IPO组24、48 h HGF水平[(2614±54)和(2524±103)pg/m]明显高于IR组[(99±47)和(70±19)pg/ml](P〈0.05);(4)IPO组24、48h肝组织ATP含量分别为(22.20±3.6)和(12.87±2.49)μg∥g,明显高于相应时点的IR组含量(P〈0.05),但低于同时点的SH组含量(P〈0.05)。结论缺血后处理对肝大部切除合并缺血再灌注后残肝的再生具有促进作用,其机制与促进HGF生成,维持肝脏的能量代谢�展开更多
文摘Obesity, which underlies various metabolic and cardio- vascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissi- pation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and dis- cuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better under- standing of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limi- tations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.
文摘目的探讨缺血后处理对大鼠肝大部切除合并缺血再灌注损伤后残肝再生的影响。方法健康清洁级雄性SD大鼠90只,体质量230-280g。按随机数字表法将其随机分为单纯肝切除组(SH)、缺血再灌注组(IR)、后处理组(IPO)。各组大鼠肝左、中叶切除,残肝(右、尾叶)做不同处理:SH组不阻断其血流,IR组阻断血流30min后恢复灌注,IPO组阻断血流30min,并于恢复灌注前进行30-30s循环3次IPO。术后1、6、12、24、48h取各组大鼠下腔静脉血及残肝组织,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、HGF、残肝组织PCNA阳性细胞比率和ATP、ADP、AMP含量,并计算残肝再生度。结果(1)IPO组1-48h各时点ALT、AST活性分别是(138±20)、(340±22)、(770±55)、(389±60)、(113±25)U/L和(247±31)、(509±51)、(972±77)、(955±159)、(222±44)U/L,明显低于IR组相应时点的ALT、AST活性,分别为(2944±37)、(560±69)、(1222±162)、(540±40)、(161±15)U/L和(439±34)、(669±94)、(1347±118)、(1274±223)、(403.4±68)U/L(均P〈0.05);(2)IPO组24、48h肝再生度(18.8%4-3.2%、34.0%4±3.5%)和PCNA阳性细胞比率(43.9%±2.7%、56.2%±4.0%)分别高于IR组的(11.3%.4±2.9%、26.8%±2.5%)和(34.5%4-2.8%、48.8%.4±1.8%)(P〈0.05);(3)IPO组24、48 h HGF水平[(2614±54)和(2524±103)pg/m]明显高于IR组[(99±47)和(70±19)pg/ml](P〈0.05);(4)IPO组24、48h肝组织ATP含量分别为(22.20±3.6)和(12.87±2.49)μg∥g,明显高于相应时点的IR组含量(P〈0.05),但低于同时点的SH组含量(P〈0.05)。结论缺血后处理对肝大部切除合并缺血再灌注后残肝的再生具有促进作用,其机制与促进HGF生成,维持肝脏的能量代谢�