Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more comple...Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required, but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1) which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferator- activated receptor-alpha (PPAR-α) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-α (TNF-α), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.展开更多
Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, pho...Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, phospholipids occupies 4% respectively. Studies have continued that thetransforms of HSC phenotype follows the changing of the cell lipid. After the activation of HSC, with HSC phenotype changing from fat-storing cells into myofibroblast, the lipid droplets decreased or disappeared gradually, which means HSCs are under the differentiating process of removing adipose, meawhile triglyceride, and the main content of lipid droplets, also obviously reduced. It was ever declined that during the process of HSC re-fating, the activated HSC would turn into quiescent state. Therefore this shows HSCs fat metabolism is closely related to the biological activity.展开更多
In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplet...In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplets and much higher numbers of mitochondria than WAT. The mitochondria in BAT uncouple large amounts of fuel oxidation from ATP for heat generation. Accumulating evidences have demonstrated that increased activity and/or amount of BAT can reverse obesity and improve insulin resistance, which highlights that BAT plays an important role in energy metabolism. In this review, we summarized recent findings that shows advantageous effects of BAT activation in metabolic diseases. In addition, we presented the function and role of brown and beige fat cells and regulatory factors for them. Finally, we discussed the potential application of brown adipocytes-based therapy and pharmacological intervention to increase BAT activity for the treatment of obesity and related diseases including insulin resistance, cardiovascular diseases and type 2 diabetes.展开更多
Activating transcription factor 5(ATF5) is a member of the activating transcription factor/cA MP response element binding protein(ATF/CREB) family, and is highly expressed in liver and adipose tissue. Previous reports...Activating transcription factor 5(ATF5) is a member of the activating transcription factor/cA MP response element binding protein(ATF/CREB) family, and is highly expressed in liver and adipose tissue. Previous reports have shown that ATF5 promoted 3T3-L1 preadipocytes differentiation. In this study, we found that ATF5 was highly expressed in mature adipocytes, suggesting a potential role of ATF5 in mature adipocytes, which has not been reported previously. To understand the function of ATF5 in mature adipocytes, we knocked down the expression of ATF5 in 3T3-L1 mature adipocytes and observed decreased lipid droplets. Consistent with the in vitro experiment, the knockdown of ATF5 in white adipose tissue led to less adipose tissue and smaller adipocytes size. Further research revealed that the inhibition of ATF5 diminished the adipocytes size via the inhibition of fatty acid synthetase, stearyl coenzyme A desaturation enzyme 1, and the induction of carnitine palmitoyl transferase 1, one key enzyme of lipid metabolism. In addition, ATF5 knockdown in inguinal white adipose tissue improved whole body insulin sensitivity.Our work provides a new understanding of ATF5 function in mature adipocytes and a potential therapeutic target of diabetes.展开更多
基金Supported by New Research Grant from the University of Nebraska Medical Center, the NIAAA, and Medical Research Funds from the Department of Veterans Affairs, United States
文摘Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required, but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1) which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferator- activated receptor-alpha (PPAR-α) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-α (TNF-α), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.
文摘Hepatic stellate cells（HSCs） are a kind of fat-storing cells, the lipid droplets are rich in the Cytoplasm, in which retinyl ester accounts for 42%, triglyceride occupies 28%, cholesterol （total） occupies 13%, phospholipids occupies 4% respectively. Studies have continued that thetransforms of HSC phenotype follows the changing of the cell lipid. After the activation of HSC, with HSC phenotype changing from fat-storing cells into myofibroblast, the lipid droplets decreased or disappeared gradually, which means HSCs are under the differentiating process of removing adipose, meawhile triglyceride, and the main content of lipid droplets, also obviously reduced. It was ever declined that during the process of HSC re-fating, the activated HSC would turn into quiescent state. Therefore this shows HSCs fat metabolism is closely related to the biological activity.
文摘In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplets and much higher numbers of mitochondria than WAT. The mitochondria in BAT uncouple large amounts of fuel oxidation from ATP for heat generation. Accumulating evidences have demonstrated that increased activity and/or amount of BAT can reverse obesity and improve insulin resistance, which highlights that BAT plays an important role in energy metabolism. In this review, we summarized recent findings that shows advantageous effects of BAT activation in metabolic diseases. In addition, we presented the function and role of brown and beige fat cells and regulatory factors for them. Finally, we discussed the potential application of brown adipocytes-based therapy and pharmacological intervention to increase BAT activity for the treatment of obesity and related diseases including insulin resistance, cardiovascular diseases and type 2 diabetes.
基金supported by the National Key Basic Research Project (2013CB530601 to X. Li)the National Natural Science Foundation of China (81270954, 31571401 to X. Li)
文摘Activating transcription factor 5(ATF5) is a member of the activating transcription factor/cA MP response element binding protein(ATF/CREB) family, and is highly expressed in liver and adipose tissue. Previous reports have shown that ATF5 promoted 3T3-L1 preadipocytes differentiation. In this study, we found that ATF5 was highly expressed in mature adipocytes, suggesting a potential role of ATF5 in mature adipocytes, which has not been reported previously. To understand the function of ATF5 in mature adipocytes, we knocked down the expression of ATF5 in 3T3-L1 mature adipocytes and observed decreased lipid droplets. Consistent with the in vitro experiment, the knockdown of ATF5 in white adipose tissue led to less adipose tissue and smaller adipocytes size. Further research revealed that the inhibition of ATF5 diminished the adipocytes size via the inhibition of fatty acid synthetase, stearyl coenzyme A desaturation enzyme 1, and the induction of carnitine palmitoyl transferase 1, one key enzyme of lipid metabolism. In addition, ATF5 knockdown in inguinal white adipose tissue improved whole body insulin sensitivity.Our work provides a new understanding of ATF5 function in mature adipocytes and a potential therapeutic target of diabetes.
