The Experts below are selected from a list of 105 Experts worldwide ranked by ideXlab platform
Margaret C. Neville - One of the best experts on this subject based on the ideXlab platform.
-
Distribution and source of Lipoprotein Lipase in mouse mammary gland.
Journal of lipid research, 1991Co-Authors: Dalan R. Jensen, Robert H Eckel, Jacqueline Etienne, Daniel H. Bessesen, Margaret C. NevilleAbstract:During lactation Lipoprotein Lipase (LPL) is elevated in mammary tissue and depressed in adipose tissue to redirect lipids for incorporation into milk fat. The cellular origin of Lipoprotein Lipase in mammary tissue is thought to be the mammary epithelial cell which is the predominant cell type noticeable in the lactating gland; however, mammary adipocytes are also present. If Lipoprotein Lipase is produced by adipocytes in other sites of the body, then the question remains as to why mammary adipocytes have not been shown to produce Lipoprotein Lipase. In this study we present several lines of evidence that indicate that the mammary adipocyte is a source of LPL in the lactating mammary gland of mice. This evidence includes the absence of extracellular and intracellular Lipoprotein Lipase activity in two types of primary mammary epithelial cell cultures and a similarity in the changes of Lipoprotein Lipase activity in genital adipose tissue from nonpregnant mice and lactating mammary tissue to the nutritional state of the animal. Other evidence presented here includes strong localization of Lipoprotein Lipase protein and messenger RNA by fluorescence immunohistochemistry and in situ hybridization, respectively, to interstitial cells located between epithelial structures. We postulate that these interstitial cells are regressed, lipid-deleted mammary adipocytes.
Robert H Eckel - One of the best experts on this subject based on the ideXlab platform.
-
striated muscle gene therapy for the treatment of Lipoprotein Lipase deficiency
PLOS ONE, 2018Co-Authors: Katherine E Gadek, Monica N Hall, Mitchell Sungello, Andrew E Libby, Drew Maclaskey, Robert H Eckel, Hong Wang, Bradley B OlwinAbstract:: Excessive circulating triglycerides due to reduction or loss of Lipoprotein Lipase activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for Lipoprotein Lipase deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in multiple tissues including striated muscle and adipose tissue, Lipoprotein Lipase is trafficked to blood vessel endothelial cells where it is anchored at the plasma membrane and hydrolyzes triglycerides into free fatty acids. We conditionally knocked out Lipoprotein Lipase in differentiated striated muscle tissue lowering striated muscle Lipoprotein Lipase activity causing hypertriglyceridemia. We then crossed Lipoprotein Lipase striated muscle knockout mice with mice possessing a conditional avian retroviral receptor gene and injected mice with either a human Lipoprotein Lipase retrovirus or an mCherry control retrovirus. Post-heparin plasma Lipoprotein Lipase activity increased for three weeks following human Lipoprotein Lipase retroviral infection compared to mCherry infected mice. Human Lipoprotein Lipase infected mice had significantly lower blood triglycerides compared to mCherry controls and were comparable to wild-type blood triglyceride levels. Thus, targeted delivery of human Lipoprotein Lipase into striated muscle tissue identifies a potential therapeutic target for Lipoprotein Lipase deficiency.
-
Distribution and source of Lipoprotein Lipase in mouse mammary gland.
Journal of lipid research, 1991Co-Authors: Dalan R. Jensen, Robert H Eckel, Jacqueline Etienne, Daniel H. Bessesen, Margaret C. NevilleAbstract:During lactation Lipoprotein Lipase (LPL) is elevated in mammary tissue and depressed in adipose tissue to redirect lipids for incorporation into milk fat. The cellular origin of Lipoprotein Lipase in mammary tissue is thought to be the mammary epithelial cell which is the predominant cell type noticeable in the lactating gland; however, mammary adipocytes are also present. If Lipoprotein Lipase is produced by adipocytes in other sites of the body, then the question remains as to why mammary adipocytes have not been shown to produce Lipoprotein Lipase. In this study we present several lines of evidence that indicate that the mammary adipocyte is a source of LPL in the lactating mammary gland of mice. This evidence includes the absence of extracellular and intracellular Lipoprotein Lipase activity in two types of primary mammary epithelial cell cultures and a similarity in the changes of Lipoprotein Lipase activity in genital adipose tissue from nonpregnant mice and lactating mammary tissue to the nutritional state of the animal. Other evidence presented here includes strong localization of Lipoprotein Lipase protein and messenger RNA by fluorescence immunohistochemistry and in situ hybridization, respectively, to interstitial cells located between epithelial structures. We postulate that these interstitial cells are regressed, lipid-deleted mammary adipocytes.
Rousseau Gama - One of the best experts on this subject based on the ideXlab platform.
-
Diurnal variation in Lipoprotein Lipase activity.
Annals of Clinical Biochemistry, 2002Co-Authors: Mp Arasaradnam, Linda M. Morgan, John Wright, Rousseau GamaAbstract:BACKGROUND We investigated whether variations in Lipoprotein Lipase activity, a key post-prandial enzyme involved in the removal of circulating dietary triglycerides, could contribute to the previously described nocturnal lipid intolerance. METHODS We studied Lipoprotein Lipase activity in 12 healthy volunteers (five women, seven men) at 11:30 h and 23:30 h on two separate occasions. Subjects consumed a high-fat mixed meal at 07:30 h for the morning study or 19:30 h for the evening study. Then, after a 4-h fast, subjects were given an intravenous bolus of 7,500 U heparin. Blood samples were collected before and 15 min after heparin administration for measurement of Lipoprotein Lipase, hepatic Lipase, triglycerides and non-esterified fatty acids concentrations. RESULTS Post-prandial post-heparin Lipoprotein Lipase activity was greater in the morning than in the evening (16.5 +/- 1.4 versus 14.4 +/- 1.0 micromol oleate/mL/h; P< 0.05). Post-prandial post-heparin hepatic Lipase activity was also greater in the morning than in the evening (8.7 +/- 1.5 versus 81 +/- 1.6 micromol oleate/mL/h; P= 0.002). There were no other significant diurnal differences. CONCLUSION We report a diurnal variation in post-prandial Lipoprotein Lipase activity. This is consistent with the notion that decreased nocturnal insulin sensitivity extends to insulin's actions on Lipoprotein Lipase and provides a possible explanation for nocturnal lipid intolerance.
-
Diurnal variation in Lipoprotein Lipase activity.
Annals of clinical biochemistry, 2002Co-Authors: Mp Arasaradnam, John Wright, L Morgan, Rousseau GamaAbstract:We investigated whether variations in Lipoprotein Lipase activity, a key post-prandial enzyme involved in the removal of circulating dietary triglycerides, could contribute to the previously described nocturnal lipid intolerance. We studied Lipoprotein Lipase activity in 12 healthy volunteers (five women, seven men) at 11:30 h and 23:30 h on two separate occasions. Subjects consumed a high-fat mixed meal at 07:30 h for the morning study or 19:30 h for the evening study. Then, after a 4-h fast, subjects were given an intravenous bolus of 7,500 U heparin. Blood samples were collected before and 15 min after heparin administration for measurement of Lipoprotein Lipase, hepatic Lipase, triglycerides and non-esterified fatty acids concentrations. Post-prandial post-heparin Lipoprotein Lipase activity was greater in the morning than in the evening (16.5 +/- 1.4 versus 14.4 +/- 1.0 micromol oleate/mL/h; P< 0.05). Post-prandial post-heparin hepatic Lipase activity was also greater in the morning than in the evening (8.7 +/- 1.5 versus 81 +/- 1.6 micromol oleate/mL/h; P= 0.002). There were no other significant diurnal differences. We report a diurnal variation in post-prandial Lipoprotein Lipase activity. This is consistent with the notion that decreased nocturnal insulin sensitivity extends to insulin's actions on Lipoprotein Lipase and provides a possible explanation for nocturnal lipid intolerance.
André Bensadoun - One of the best experts on this subject based on the ideXlab platform.
-
Lipoprotein Lipase lpl on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy
Journal of Clinical Investigation, 2003Co-Authors: Hiroaki Yagyu, Guangping Chen, Masayoshi Yokoyama, Kumiko Hirata, Ayanna S Augustus, Yuko Kako, Toru Seo, Peer E Lutz, Martin Merkel, André BensadounAbstract:Lipoprotein Lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although Lipoprotein Lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for Lipoprotein Lipase actions. To study whether nontransferable Lipoprotein Lipase has physiological actions, we placed an alpha-myosin heavy-chain promoter upstream of a human Lipoprotein Lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered Lipoprotein Lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human Lipoprotein Lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, Lipoprotein Lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.
-
Effect of chlorate on the sulfation of Lipoprotein Lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects Lipoprotein Lipase degradation.
Journal of Biological Chemistry, 1991Co-Authors: A J Hoogewerf, L A Cisar, D C Evans, André BensadounAbstract:Abstract In avian-cultured adipocytes 76% of the newly synthesized Lipoprotein Lipase is degraded before release into the medium (Cupp, M., Bensadoun, A., and Melford, K. (1987) J. Biol. Chem. 262, 6383-6388). The same group (Cisar, L. A., Hoogewerf, A. J., Cupp, M., Rapport, C. A., and Bensadoun, A. (1989) J. Biol. Chem. 264, 1767-1774) has proposed that the interaction of Lipoprotein Lipase with a class of cell surface heparan sulfate proteoglycans is necessary for degradation to occur. To test further this hypothesis, the binding capacity of the plasma membrane for the Lipase was decreased by inhibiting the sulfation of glycosaminoglycans with sodium chlorate, an inhibitor of sulfate adenyltransferase. Chlorate decreased sulfate incorporation into trypsin-releasable heparan sulfate proteoglycans to 20% of control levels. The amount of uronic acid in the trypsin-releasable heparan sulfate proteoglycans remained constant. Therefore, chlorate decreased sulfation density on heparan sulfate chains by approximately 5-fold. In the same fractions, chlorate increased the median heparan sulfate Mr measured on Sephacryl S-300. Chlorate decreased the maximum binding of 125I-Lipoprotein Lipase to adipocytes by 4-fold, but no significant effects on the affinity constants were observed. Chlorate increased Lipoprotein Lipase secretion in a dose-dependent relationship up to 30 mM. Utilizing a pulse-chase protocol, it was shown that Lipase synthesis in control and chlorate-treated cells was not significantly different and that the increased secretion could be accounted for by a decreased Lipoprotein Lipase degradation rate. In control cells 77 +/- 11% of the synthesized enzyme was degraded whereas in chlorate-treated cells degradation was reduced to 42 +/- 9% of the synthesized amount. The present study shows that decreased sulfation of heparan sulfate proteoglycans decreases the maximum binding of the Lipase for the adipocyte cell surface. Consistent with the model that binding of Lipoprotein Lipase to cell surface heparan sulfate is required for Lipase degradation, degradation is reduced in chlorate-treated cultures. In this report it is also shown that chlorate inhibits Lipoprotein Lipase sulfation and that desulfation of the enzyme has no effect on its catalytic efficiency or on its binding to cultured adipocytes.
Dalan R. Jensen - One of the best experts on this subject based on the ideXlab platform.
-
Distribution and source of Lipoprotein Lipase in mouse mammary gland.
Journal of lipid research, 1991Co-Authors: Dalan R. Jensen, Robert H Eckel, Jacqueline Etienne, Daniel H. Bessesen, Margaret C. NevilleAbstract:During lactation Lipoprotein Lipase (LPL) is elevated in mammary tissue and depressed in adipose tissue to redirect lipids for incorporation into milk fat. The cellular origin of Lipoprotein Lipase in mammary tissue is thought to be the mammary epithelial cell which is the predominant cell type noticeable in the lactating gland; however, mammary adipocytes are also present. If Lipoprotein Lipase is produced by adipocytes in other sites of the body, then the question remains as to why mammary adipocytes have not been shown to produce Lipoprotein Lipase. In this study we present several lines of evidence that indicate that the mammary adipocyte is a source of LPL in the lactating mammary gland of mice. This evidence includes the absence of extracellular and intracellular Lipoprotein Lipase activity in two types of primary mammary epithelial cell cultures and a similarity in the changes of Lipoprotein Lipase activity in genital adipose tissue from nonpregnant mice and lactating mammary tissue to the nutritional state of the animal. Other evidence presented here includes strong localization of Lipoprotein Lipase protein and messenger RNA by fluorescence immunohistochemistry and in situ hybridization, respectively, to interstitial cells located between epithelial structures. We postulate that these interstitial cells are regressed, lipid-deleted mammary adipocytes.