Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidin...Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidine phosphate guanosine (CpG) oligodinucleotide (ODN1826), a Toll-like receptor 9 (TLR9) agonist was administered in combination with D-galactosamine (GalN) that caused relatively liver-specific inflammation and toxicity. In the control mice group injected with phosphate-buffered saline (PBS) (acute psychological stress model associated with blood sampling), the serum triglyceride (TG) levels showed a rapid decrease followed by a rebound at 24 h as we have recently reported. However, such a TG rebound was impaired in the CpG/GalN- and solely CpG-treated groups of mice despite an absence of liver injury based on serum alanine aminotransferase levels in the latter group. Thus, the stress-associated serum TG rebound was abrogated by the injection of a sub-hepatotoxic CpG dose. In the second experiment, we simply measured the hepatic CD36 and SACRB1 (the gene for scavenger receptor B1 (SR-B1)) transcripts after the i.p. administration of PBS, CpG or CpG/GalN. There was a remarkable elevation of hepatic CD36 transcript expression in both the CpG- and CpG/GalN-treated mice at 8 h post-CpG injection whereas the increase in the PBS-treated mice was slower than the former two groups, suggesting that hepatic CD36 transcript expression is more pronounced in the combined stress models than under psychological stress alone. The individual mice data showed that the increase in CD36 expression was accompanied by a reduction in SCARB1 mRNA, showing reciprocal regulation between these two genes. Together with our previously reported findings, these data suggest that, in a murine model combining psychological stress with TLR-triggered hepatic inflammation, the psychological stress facilitates liver uptake of plasma TG (and its components fatty acids), but the subsequent re-esterification and/or release of TG-rich lipopr展开更多
In this article, we report the changes in serum triglyceride (TG) levels that occurred during repeated tail blood sampling using a mouse restrainer. We used three groups of mice, namely, “PBS-restrained” “PBS-unres...In this article, we report the changes in serum triglyceride (TG) levels that occurred during repeated tail blood sampling using a mouse restrainer. We used three groups of mice, namely, “PBS-restrained” “PBS-unrestrained” and “mock-restrained”. The mice in the PBS-restrained and PBS-unrestrained groups were intraperitoneally (i.p.) injected with 100 mL PBS and tail blood sampling was performed at 1, 5, 8, 24, and 48 h after i.p. injection. For the mock-restrained group, no i.p. injection was performed whereas the subsequent tail blood sampling was similarly performed. During the tail blood sampling, the mice of the two “restrained” groups were placed inside the restrainer designed from an open-ended 50 mL conical tube. The blood from the mice in the PBS-unrestrained group mice was sampled from the tail held by the operator’s hands while being allowed to move on a stage. Strikingly, in all of the three groups, the serum TG level initially decreased to remarkably low levels (approximately 30 mg/dL) after several blood samplings were performed over 8 h. This decrease was followed by a 2 - 3-fold increase in the levels relative to that in the control mice in the subsequent 24 - 48 h time period. We concluded that the acute stress associated with blood sampling caused alterations in TG levels. Serum levels of free fatty acid showed only modest changes. Changes in TG levels were not associated with serum corticosterone levels but with a dramatic increase in CD36 transcript levels in the liver. The relevance of this finding to the previously reported release of lipoprotein lipase (LPL) from white fatty tissue into the plasma during acute stress is also discussed.展开更多
文摘Changes in lipid metabolism have been implicated in protection against infectious diseases. In the first experiment of this study, we measured clinical lipid parameters in a murine model where the unmethylated cytidine phosphate guanosine (CpG) oligodinucleotide (ODN1826), a Toll-like receptor 9 (TLR9) agonist was administered in combination with D-galactosamine (GalN) that caused relatively liver-specific inflammation and toxicity. In the control mice group injected with phosphate-buffered saline (PBS) (acute psychological stress model associated with blood sampling), the serum triglyceride (TG) levels showed a rapid decrease followed by a rebound at 24 h as we have recently reported. However, such a TG rebound was impaired in the CpG/GalN- and solely CpG-treated groups of mice despite an absence of liver injury based on serum alanine aminotransferase levels in the latter group. Thus, the stress-associated serum TG rebound was abrogated by the injection of a sub-hepatotoxic CpG dose. In the second experiment, we simply measured the hepatic CD36 and SACRB1 (the gene for scavenger receptor B1 (SR-B1)) transcripts after the i.p. administration of PBS, CpG or CpG/GalN. There was a remarkable elevation of hepatic CD36 transcript expression in both the CpG- and CpG/GalN-treated mice at 8 h post-CpG injection whereas the increase in the PBS-treated mice was slower than the former two groups, suggesting that hepatic CD36 transcript expression is more pronounced in the combined stress models than under psychological stress alone. The individual mice data showed that the increase in CD36 expression was accompanied by a reduction in SCARB1 mRNA, showing reciprocal regulation between these two genes. Together with our previously reported findings, these data suggest that, in a murine model combining psychological stress with TLR-triggered hepatic inflammation, the psychological stress facilitates liver uptake of plasma TG (and its components fatty acids), but the subsequent re-esterification and/or release of TG-rich lipopr
文摘In this article, we report the changes in serum triglyceride (TG) levels that occurred during repeated tail blood sampling using a mouse restrainer. We used three groups of mice, namely, “PBS-restrained” “PBS-unrestrained” and “mock-restrained”. The mice in the PBS-restrained and PBS-unrestrained groups were intraperitoneally (i.p.) injected with 100 mL PBS and tail blood sampling was performed at 1, 5, 8, 24, and 48 h after i.p. injection. For the mock-restrained group, no i.p. injection was performed whereas the subsequent tail blood sampling was similarly performed. During the tail blood sampling, the mice of the two “restrained” groups were placed inside the restrainer designed from an open-ended 50 mL conical tube. The blood from the mice in the PBS-unrestrained group mice was sampled from the tail held by the operator’s hands while being allowed to move on a stage. Strikingly, in all of the three groups, the serum TG level initially decreased to remarkably low levels (approximately 30 mg/dL) after several blood samplings were performed over 8 h. This decrease was followed by a 2 - 3-fold increase in the levels relative to that in the control mice in the subsequent 24 - 48 h time period. We concluded that the acute stress associated with blood sampling caused alterations in TG levels. Serum levels of free fatty acid showed only modest changes. Changes in TG levels were not associated with serum corticosterone levels but with a dramatic increase in CD36 transcript levels in the liver. The relevance of this finding to the previously reported release of lipoprotein lipase (LPL) from white fatty tissue into the plasma during acute stress is also discussed.
