Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to t...Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracelhilar matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.展开更多
Negative energy balance in early lactating dairy cows results in a massive release of fatty acids （FA） into the blood in nonesterified fatty acids （NEFA） form. Large quantities of circulating NEFA may alter the se...Negative energy balance in early lactating dairy cows results in a massive release of fatty acids （FA） into the blood in nonesterified fatty acids （NEFA） form. Large quantities of circulating NEFA may alter the serum FA profile of phospholipids （PL） fraction, which is responsible for cellular plasma membrane integrity and intercellular signaling. The objective of this study was to determine the effects of subcutaneous fat stores, as assessed by body condition score （BCS） on a scale of one to five, around the time of calving and the subsequent lipomobilization on FA profile of serum NEFA and PL lipid fractions, and on productive performance. Based on BCS, cows were retrospectively dichotomized into two groups： over-conditioned （BCS _〉 3.25） and control （BCS _〈 3.0）. 22 cows had serum samples obtained at -28, -7, 8, 18 and 28 d relative to parturition and analyzed for the FA profile of the NEFA and PL fractions. As expected, over-conditioned cows had greater total plasma NEFA concentrations and decreased dry matter intake. Milk yield and composition did not differ between groups. More importantly however, several FA in the NEFA fraction of plasma lipids varied significantly, including C14：1, C16：0, C18：0 and C20：3n3. In the PL fraction, other FA varied significantly by BCS around time of parturition, including C16：0, C17：0, total C18：2 cis, and C20：2. In summary, BCS did affect FA profile of serum NEFA and PL lipid fractions. This may have drastic consequences for circulating immune cells and their ability to fight infection by altering their FA profile.展开更多
OBJECTIVES: To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro, and to examine whether the combined presence of elevated ...OBJECTIVES: To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro, and to examine whether the combined presence of elevated FFAs and glucose may cross-amplify their individual injurious effects. METHODS: Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24 - 96 h. Morphologic alterations were observed using a phase contrast microscope and an electron microscope. Inhibition of proliferation was measured by a colorimetric 3-[4, 5-dimethyl thiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell viability was determined using trypan blue exclusion. Distribution of cells along phases of the cell cycle was analyzed by flow cytometry. RESULTS: Glucose 15 or 30 mmol/L, palmitate (PA) 0.25 or 0.5 mmol/L, and oleate (OA) 0.5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose-and-time-dependent manner. After treatment with elevated glucose and/or FFAs, the G(0)/G(1) phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G(0)/G(1) phase. The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L + PA 0.25 mmol/L, glucose 30 mmol/L + OA 0.5 mmol/L, glucose 30 mmol/L + PA 0.25 mmol/L + OA 0.5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone. CONCLUSION: Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro. These changes were cross-amplified in the combined presence of high levels of glucose and FFAs.展开更多
s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs ...s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs and glucose may cross amplify their individual injurious effects Methods Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24-96 h Morphologic alterations were observed using a phase contrast microscope and an electron microscope Inhibition of proliferation was measured by a colorimetric 3 [4, 5 dimethyl thiazol 2 yl] 2, 5 diphenyltetrazolium bromide (MTT) assay Cell viability was determined using trypan blue exclusion Distribution of cells along phases of the cell cycle was analyzed by flow cytometry Results Glucose 15 or 30 mmol/L, palmitate (PA) 0 25 or 0 5 mmol/L, and oleate (OA) 0 5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose and time dependent manner After treatment with elevated glucose and/or FFAs, the G 0/G 1 phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G 0/G 1 phase The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L+PA 0 25 mmol/L, glucose 30 mmol/L+OA 0 5 mmol/L, glucose 30 mmol/L+PA 0 25 mmol/L+OA 0 5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone Conclusion Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro These changes were cross amplified in the combined presence of high levels of glucose and FFAs展开更多
基金Partially supported by the National Natural Science Foundation of China(81373465)
文摘Abstract The lipids present in hepatic stellate cells （HSCs） lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracelhilar matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.
文摘Negative energy balance in early lactating dairy cows results in a massive release of fatty acids （FA） into the blood in nonesterified fatty acids （NEFA） form. Large quantities of circulating NEFA may alter the serum FA profile of phospholipids （PL） fraction, which is responsible for cellular plasma membrane integrity and intercellular signaling. The objective of this study was to determine the effects of subcutaneous fat stores, as assessed by body condition score （BCS） on a scale of one to five, around the time of calving and the subsequent lipomobilization on FA profile of serum NEFA and PL lipid fractions, and on productive performance. Based on BCS, cows were retrospectively dichotomized into two groups： over-conditioned （BCS _〉 3.25） and control （BCS _〈 3.0）. 22 cows had serum samples obtained at -28, -7, 8, 18 and 28 d relative to parturition and analyzed for the FA profile of the NEFA and PL fractions. As expected, over-conditioned cows had greater total plasma NEFA concentrations and decreased dry matter intake. Milk yield and composition did not differ between groups. More importantly however, several FA in the NEFA fraction of plasma lipids varied significantly, including C14：1, C16：0, C18：0 and C20：3n3. In the PL fraction, other FA varied significantly by BCS around time of parturition, including C16：0, C17：0, total C18：2 cis, and C20：2. In summary, BCS did affect FA profile of serum NEFA and PL lipid fractions. This may have drastic consequences for circulating immune cells and their ability to fight infection by altering their FA profile.
文摘OBJECTIVES: To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro, and to examine whether the combined presence of elevated FFAs and glucose may cross-amplify their individual injurious effects. METHODS: Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24 - 96 h. Morphologic alterations were observed using a phase contrast microscope and an electron microscope. Inhibition of proliferation was measured by a colorimetric 3-[4, 5-dimethyl thiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell viability was determined using trypan blue exclusion. Distribution of cells along phases of the cell cycle was analyzed by flow cytometry. RESULTS: Glucose 15 or 30 mmol/L, palmitate (PA) 0.25 or 0.5 mmol/L, and oleate (OA) 0.5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose-and-time-dependent manner. After treatment with elevated glucose and/or FFAs, the G(0)/G(1) phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G(0)/G(1) phase. The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L + PA 0.25 mmol/L, glucose 30 mmol/L + OA 0.5 mmol/L, glucose 30 mmol/L + PA 0.25 mmol/L + OA 0.5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone. CONCLUSION: Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro. These changes were cross-amplified in the combined presence of high levels of glucose and FFAs.
文摘s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs and glucose may cross amplify their individual injurious effects Methods Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24-96 h Morphologic alterations were observed using a phase contrast microscope and an electron microscope Inhibition of proliferation was measured by a colorimetric 3 [4, 5 dimethyl thiazol 2 yl] 2, 5 diphenyltetrazolium bromide (MTT) assay Cell viability was determined using trypan blue exclusion Distribution of cells along phases of the cell cycle was analyzed by flow cytometry Results Glucose 15 or 30 mmol/L, palmitate (PA) 0 25 or 0 5 mmol/L, and oleate (OA) 0 5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose and time dependent manner After treatment with elevated glucose and/or FFAs, the G 0/G 1 phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G 0/G 1 phase The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L+PA 0 25 mmol/L, glucose 30 mmol/L+OA 0 5 mmol/L, glucose 30 mmol/L+PA 0 25 mmol/L+OA 0 5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone Conclusion Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro These changes were cross amplified in the combined presence of high levels of glucose and FFAs
