Hormone-sensitive Lipase Deficiency in Mice Changes the Plasma Lipid Profile by Affecting the Tissue-specific Expression Pattern of Lipoprotein Lipase in Adipose Tissue and Muscle

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (−40%) and TG (−63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (−90%) and strongly decreased ketone body concentrations in plasma (−80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an “anti-atherogenic” lipoprotein profile. Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (−40%) and TG (−63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (−90%) and strongly decreased ketone body concentrations in plasma (−80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an “anti-atherogenic” lipoprotein profile. white adipose tissue hormone-sensitive lipase triglycerides adipose tissue brown adipose tissue non-esterified fatty acids knock-out wild type lipoprotein lipase total cholesterol high density lipoprotein very low density lipoprotein fractional catabolic rate absolute catabolic rate phospholipid fast protein liquid chromatography wild type In mammals, white adipose tissue (WAT)1 is the most important storage organ of TG. The mobilization of TG during fasting or periods of increased energy demand, and the release of non-esterified fatty acids (NEFA) is an essential process that supplies non-adipose organs with substrates for energy conversion (1.Sztalryd C. Kraemer F.B. Am. J. Physiol. 1994; 266: 179-185Crossref PubMed Google Scholar, 2.Langfort J. Ploug T. Ihlemann J. Enevoldsen L.H. Stallknecht B. Saldo M. Kjaer M. Holm C. Galbo H. Adv. Exp. Med. Biol. 1998; 441: 219-228Crossref PubMed Scopus (46) Google Scholar). NEFA absorbed by skeletal and cardiac muscle are predominantly used for oxidation and energy production. In the liver, NEFA are also used for oxidation but, in addition, are utilized for several other metabolic processes. NEFA can be stored as hepatic TG droplets, used for the synthesis of ketone bodies, or incorporated into VLDL (3.Bulow J. Simonsen L. Wiggins D. Humphreys S.M. Frayn K.N. Powell D. Gibbons G.F. J. Lipid Res. 1999; 40: 2034-2043Abstract Full Text Full Text PDF PubMed Google Scholar, 4.Gibbons G.F. Islam K. Pease R.J. Biochim. Biophys. Acta. 2000; PubMed Scopus Google Scholar). VLDL are from the into the vascular are by associated lipoprotein lipase (LPL) Scopus Google Scholar, T. J. Scholar). process supplies as with NEFA, an of fatty important enzyme for the mobilization of TG and NEFA in is hormone-sensitive lipase lipase diglycerides, cholesteryl esters B. H. PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar, K. D. J. Lipid Res. Full Text PDF PubMed Google Scholar, K. H. Kraemer F.B. J. Biol. Full Text Full Text PDF PubMed Scopus Google and the levels of expression are in and brown adipose tissue the enzyme is also in many other including muscle J. Ploug T. Ihlemann J. Enevoldsen L.H. Stallknecht B. Saldo M. Kjaer M. Holm C. Galbo H. Adv. Exp. Med. Biol. 1998; 441: 219-228Crossref PubMed Scopus (46) Google Holm C. J. Med. 1994; Google C. Biophys. Res. PubMed Scopus Google and H. H. B. Holm C. 1999; PubMed Scopus Google Scholar). In the HSL activity for most of the lipolysis in and lipid K.N. Humphreys S.M. Am. J. Physiol. 1994; 266: Google Scholar, K.N. Humphreys S.M. PubMed Scopus Google Scholar). In the enzyme activity is by as of activity 1999; PubMed Google Scholar, PubMed Scopus Google Scholar, J. Biol. Full Text PDF PubMed Google Scholar, J. Physiol. PubMed Scopus Google Scholar, J. Physiol. PubMed Scopus Google results in a in the levels that protein K. Res. 1998; Google Scholar). of HSL the of a HSL and 1999; Full Text Full Text PDF PubMed Scopus Google which the enzyme from the to the lipid In to HSL to and to the lipid the HSL and with the enzyme the of HSL in the of TG was by in HSL knock-out mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar). HSL deficiency was with body and that lipase in to for the of TG in the of HSL-ko mice exhibited increased of and changes in the lipid of and other of the body J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). in lipolysis with decreased NEFA and release when HSL was for a role of HSL in the of TG and and the release of NEFA M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). a the plasma levels of NEFA are decreased in fasting mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google the plasma NEFA strongly affect lipid synthesis and in hepatic and T. M. D. Biophys. Res. 1998; PubMed Scopus Google Scholar). decreased NEFA release in HSL-ko mice is expected to result in decreased hepatic VLDL synthesis and other metabolic we the role of HSL deficiency the metabolism of plasma lipids and lipoproteins in HSL-ko demonstrate that decreased plasma NEFA levels in mice are associated with decreased hepatic VLDL decreased and the depletion of TG stores in the liver. the of plasma VLDL is increased of the coordinate up-regulation of the tissue-specific LPL activity in muscle and which results in plasma TG levels and increased HDL cholesterol concentrations in fed and fasted HSL-ko of HSL for the metabolism of stores is from in mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. L. L. Res. PubMed Scopus Google Scholar, H. M. PubMed Scopus Google Scholar). In the of the of TG and is to a of plasma NEFA concentrations in fasted animals J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar). In the present study we that decreased plasma NEFA concentrations in the plasma lipoprotein with decreased plasma TG levels and increased total and HDL cholesterol In the liver, HSL-ko mice exhibited decreased VLDL decreased TG storage droplets, and decreased NEFA that are by of of NEFA the to the of lipid storage feeds into or to lipid storage the of fatty acids for VLDL G.F. PubMed Scopus Google Scholar). TG by a TG and the Res. 1998; PubMed Scopus Google TG are incorporated into VLDL by a process that lipid protein PubMed Scopus Google Scholar). Our are with and that in a of decreased plasma NEFA as observed in fasted HSL-ko stores and VLDL synthesis are decreased. is to that of fatty acids to lipid and VLDL as hepatic fatty synthesis from the vascular system, for the deficiency of fatty transport from to the the of NEFA that for or was to a in the ketone body in plasma that of fatty is also when HSL-mediated of NEFA from stores is increased ketone body by also to the in ketone body in plasma of fasted In of the of ketone as an energy in the low rates of hepatic ketone body in HSL-ko mice a during fasting in hepatic VLDL as a result of the TG lipolysis in of HSL-ko mice was also associated with in the catabolic of VLDL increased in HSL-ko mice with The increased is mainly by the TG in In when the was as a of the a decreased was in Because in the is a of the result of decreased VLDL synthesis in decreased TG in fasted HSL-ko animals was not a result of decreased VLDL was also caused by the induction of LPL in cardiac and skeletal muscle. The of LPL in muscle an to the of energy in a of low plasma concentrations of NEFA and TG-rich lipoproteins. The of LPL in was to be of the LPL was markedly in of HSL-ko In LPL was induced in fasted mice in fed mice with LPL activity in the muscle and of fasted mice is expected to plasma TG in to the decreased VLDL synthesis in HSL-ko the tissue-specific LPL activity in cardiac muscle to be in the of TG-rich lipoproteins H. 1999; PubMed Scopus Google Scholar). LPL activity in is the total tissue LPL activity is the tissue is increased in mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, J. L. L. Res. PubMed Scopus Google Scholar). is to that the total activity of the body is by the tissue-specific in cardiac muscle, skeletal muscle, and which are increased in fasted HSL-ko for the coordinate of LPL in the or of HSL to be In AT, a of LPL and HSL was a of storage and mobilization K.N. Humphreys S.M. Adv. PubMed Scopus Google Scholar). coordinate of the tissue not of LPL activity in muscle and and of LPL in is a LPL levels were in these in HSL-ko and in LPL are a result of changes in enzyme or enzyme to the in the of LPL observed in in to and as and J. 1999; PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar). The that the induction of LPL in mice are several are the lack of induction of LPL in of HSL-ko mice in to a in is that the up-regulation of LPL is by the lipid stores in the as a the increased for fatty acids for lipid stores in H. M. PubMed Scopus Google Scholar, H. B. Holm C. PubMed Scopus Google Scholar). the decreased of fatty acids or a essential fatty from plasma or changes in the of HSL deficiency the of The is also with in to other LPL is in of that increased and lipid as observed in HSL-ko mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google LPL expression the induction of LPL was in cardiac muscle, in with the that the heart is NEFA as the of cardiac muscle TG stores were decreased in HSL-ko The heart also the to of fatty acids as TG M. J. Biol. 266: Full Text PDF PubMed Google Scholar). TG is a fatty and fatty In fasted HSL-ko the cardiac TG was markedly an of fatty which was not by the up-regulation of the tissue LPL plasma TG levels as a result of decreased hepatic VLDL synthesis and increased VLDL are associated with increased plasma cholesterol and HDL cholesterol These are in with the that increased of TG-rich lipoproteins to the induction of LPL is an important of HDL cholesterol is generally that the lipolysis of and VLDL as that with hepatic are to by the of lipid and B. H. B. Biochim. Biophys. Acta. PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, 2000; PubMed Scopus Google Scholar, M. S.M. L.H. K. M. L. C. K. M. D. J. K. B. 1999; PubMed Scopus Google Scholar, M. J. T. C. M. K. C. 1999; PubMed Scopus Google Scholar, M. H. J. 1999; PubMed Scopus Google Scholar, 2000; PubMed Scopus Google Scholar). is to that the increased LPL in muscle and for the observed in HDL cholesterol we that the changes observed in mice an important for the enzyme in the of lipid and lipoprotein In mammals, white adipose tissue (WAT)1 is the most important storage organ of TG. The mobilization of TG during fasting or periods of increased energy demand, and the release of non-esterified fatty acids (NEFA) is an essential process that supplies non-adipose organs with substrates for energy conversion (1.Sztalryd C. Kraemer F.B. Am. J. Physiol. 1994; 266: 179-185Crossref PubMed Google Scholar, 2.Langfort J. Ploug T. Ihlemann J. Enevoldsen L.H. Stallknecht B. Saldo M. Kjaer M. Holm C. Galbo H. Adv. Exp. Med. Biol. 1998; 441: 219-228Crossref PubMed Scopus (46) Google Scholar). NEFA absorbed by skeletal and cardiac muscle are predominantly used for oxidation and energy production. In the liver, NEFA are also used for oxidation but, in addition, are utilized for several other metabolic processes. NEFA can be stored as hepatic TG droplets, used for the synthesis of ketone bodies, or incorporated into VLDL (3.Bulow J. Simonsen L. Wiggins D. Humphreys S.M. Frayn K.N. Powell D. Gibbons G.F. J. Lipid Res. 1999; 40: 2034-2043Abstract Full Text Full Text PDF PubMed Google Scholar, 4.Gibbons G.F. Islam K. Pease R.J. Biochim. Biophys. Acta. 2000; PubMed Scopus Google Scholar). VLDL are from the into the vascular are by associated lipoprotein lipase (LPL) Scopus Google Scholar, T. J. Scholar). process supplies as with NEFA, an of fatty important enzyme for the mobilization of TG and NEFA in is hormone-sensitive lipase lipase diglycerides, cholesteryl esters B. H. PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar, K. D. J. Lipid Res. Full Text PDF PubMed Google Scholar, K. H. Kraemer F.B. J. Biol. Full Text Full Text PDF PubMed Scopus Google and the levels of expression are in and brown adipose tissue the enzyme is also in many other including muscle J. Ploug T. Ihlemann J. Enevoldsen L.H. Stallknecht B. Saldo M. Kjaer M. Holm C. Galbo H. Adv. Exp. Med. Biol. 1998; 441: 219-228Crossref PubMed Scopus (46) Google Holm C. J. Med. 1994; Google C. Biophys. Res. PubMed Scopus Google and H. H. B. Holm C. 1999; PubMed Scopus Google Scholar). In the HSL activity for most of the lipolysis in and lipid K.N. Humphreys S.M. Am. J. Physiol. 1994; 266: Google Scholar, K.N. Humphreys S.M. PubMed Scopus Google Scholar). In the enzyme activity is by as of activity 1999; PubMed Google Scholar, PubMed Scopus Google Scholar, J. Biol. Full Text PDF PubMed Google Scholar, J. Physiol. PubMed Scopus Google Scholar, J. Physiol. PubMed Scopus Google results in a in the levels that protein K. Res. 1998; Google Scholar). of HSL the of a HSL and 1999; Full Text Full Text PDF PubMed Scopus Google which the enzyme from the to the lipid In to HSL to and to the lipid the HSL and with the enzyme the of HSL in the of TG was by in HSL knock-out mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar). HSL deficiency was with body and that lipase in to for the of TG in the of HSL-ko mice exhibited increased of and changes in the lipid of and other of the body J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). in lipolysis with decreased NEFA and release when HSL was for a role of HSL in the of TG and and the release of NEFA M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). a the plasma levels of NEFA are decreased in fasting mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar). the plasma NEFA strongly affect lipid synthesis and in hepatic and T. M. D. Biophys. Res. 1998; PubMed Scopus Google Scholar). decreased NEFA release in HSL-ko mice is expected to result in decreased hepatic VLDL synthesis and other metabolic we the role of HSL deficiency the metabolism of plasma lipids and lipoproteins in HSL-ko demonstrate that decreased plasma NEFA levels in mice are associated with decreased hepatic VLDL decreased and the depletion of TG stores in the liver. the of plasma VLDL is increased of the coordinate up-regulation of the tissue-specific LPL activity in muscle and which results in plasma TG levels and increased HDL cholesterol concentrations in fed and fasted HSL-ko of HSL for the metabolism of stores is from in mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. L. L. Res. PubMed Scopus Google Scholar, H. M. PubMed Scopus Google Scholar). In the of the of TG and is to a of plasma NEFA concentrations in fasted animals J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar). In the present study we that decreased plasma NEFA concentrations in the plasma lipoprotein with decreased plasma TG levels and increased total and HDL cholesterol In the liver, HSL-ko mice exhibited decreased VLDL decreased TG storage droplets, and decreased NEFA that are by of of NEFA the to the of lipid storage feeds into or to lipid storage the of fatty acids for VLDL G.F. PubMed Scopus Google Scholar). TG by a TG and the Res. 1998; PubMed Scopus Google TG are incorporated into VLDL by a process that lipid protein PubMed Scopus Google Scholar). Our are with and that in a of decreased plasma NEFA as observed in fasted HSL-ko stores and VLDL synthesis are decreased. is to that of fatty acids to lipid and VLDL as hepatic fatty synthesis from the vascular system, for the deficiency of fatty transport from to the the of NEFA that for or was to a in the ketone body in plasma that of fatty is also when HSL-mediated of NEFA from stores is increased ketone body by also to the in ketone body in plasma of fasted In of the of ketone as an energy in the low rates of hepatic ketone body in HSL-ko mice a during fasting in hepatic VLDL as a result of the TG lipolysis in of HSL-ko mice was also associated with in the catabolic of VLDL increased in HSL-ko mice with The increased is mainly by the TG in In when the was as a of the a decreased was in Because in the is a of the result of decreased VLDL synthesis in decreased TG in fasted HSL-ko animals was not a result of decreased VLDL was also caused by the induction of LPL in cardiac and skeletal muscle. The of LPL in muscle an to the of energy in a of low plasma concentrations of NEFA and TG-rich lipoproteins. The of LPL in was to be of the LPL was markedly in of HSL-ko In LPL was induced in fasted mice in fed mice with LPL activity in the muscle and of fasted mice is expected to plasma TG in to the decreased VLDL synthesis in HSL-ko the tissue-specific LPL activity in cardiac muscle to be in the of TG-rich lipoproteins H. 1999; PubMed Scopus Google Scholar). LPL activity in is the total tissue LPL activity is the tissue is increased in mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, J. L. L. Res. PubMed Scopus Google Scholar). is to that the total activity of the body is by the tissue-specific in cardiac muscle, skeletal muscle, and which are increased in fasted HSL-ko for the coordinate of LPL in the or of HSL to be In AT, a of LPL and HSL was a of storage and mobilization K.N. Humphreys S.M. Adv. PubMed Scopus Google Scholar). coordinate of the tissue not of LPL activity in muscle and and of LPL in is a LPL levels were in these in HSL-ko and in LPL are a result of changes in enzyme or enzyme to the in the of LPL observed in in to and as and J. 1999; PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar). The that the induction of LPL in mice are several are the lack of induction of LPL in of HSL-ko mice in to a in is that the up-regulation of LPL is by the lipid stores in the as a the increased for fatty acids for lipid stores in H. M. PubMed Scopus Google Scholar, H. B. Holm C. PubMed Scopus Google Scholar). the decreased of fatty acids or a essential fatty from plasma or changes in the of HSL deficiency the of The is also with in to other LPL is in of that increased and lipid as observed in HSL-ko mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google LPL expression the induction of LPL was in cardiac muscle, in with the that the heart is NEFA as the of cardiac muscle TG stores were decreased in HSL-ko The heart also the to of fatty acids as TG M. J. Biol. 266: Full Text PDF PubMed Google Scholar). TG is a fatty and fatty In fasted HSL-ko the cardiac TG was markedly an of fatty which was not by the up-regulation of the tissue LPL plasma TG levels as a result of decreased hepatic VLDL synthesis and increased VLDL are associated with increased plasma cholesterol and HDL cholesterol These are in with the that increased of TG-rich lipoproteins to the induction of LPL is an important of HDL cholesterol is generally that the lipolysis of and VLDL as that with hepatic are to by the of lipid and B. H. B. Biochim. Biophys. Acta. PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, 2000; PubMed Scopus Google Scholar, M. S.M. L.H. K. M. L. C. K. M. D. J. K. B. 1999; PubMed Scopus Google Scholar, M. J. T. C. M. K. C. 1999; PubMed Scopus Google Scholar, M. H. J. 1999; PubMed Scopus Google Scholar, 2000; PubMed Scopus Google Scholar). is to that the increased LPL in muscle and for the observed in HDL cholesterol we that the changes observed in mice an important for the enzyme in the of lipid and lipoprotein The of HSL for the metabolism of stores is from in mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, M. C. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. L. L. Res. PubMed Scopus Google Scholar, H. M. PubMed Scopus Google Scholar). In the of the of TG and is to a of plasma NEFA concentrations in fasted animals J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar). In the present study we that decreased plasma NEFA concentrations in the plasma lipoprotein with decreased plasma TG levels and increased total and HDL cholesterol In the liver, HSL-ko mice exhibited decreased VLDL decreased TG storage droplets, and decreased NEFA that are by of of NEFA the to the of lipid storage feeds into or to lipid storage the of fatty acids for VLDL G.F. PubMed Scopus Google Scholar). TG by a TG and the Res. 1998; PubMed Scopus Google TG are incorporated into VLDL by a process that lipid protein PubMed Scopus Google Scholar). Our are with and that in a of decreased plasma NEFA as observed in fasted HSL-ko stores and VLDL synthesis are decreased. is to that of fatty acids to lipid and VLDL as hepatic fatty synthesis from the vascular system, for the deficiency of fatty transport from to the liver. the of NEFA that for or was to a in the ketone body in plasma that of fatty is also when HSL-mediated of NEFA from stores is increased ketone body by also to the in ketone body in plasma of fasted In of the of ketone as an energy in the low rates of hepatic ketone body in HSL-ko mice a during fasting in Decreased hepatic VLDL as a result of the TG lipolysis in of HSL-ko mice was also associated with in the catabolic of VLDL increased in HSL-ko mice with The increased is mainly by the TG in In when the was as a of the a decreased was in Because in the is a of the result of decreased VLDL synthesis in The decreased TG in fasted HSL-ko animals was not a result of decreased VLDL was also caused by the induction of LPL in cardiac and skeletal muscle. The of LPL in muscle an to the of energy in a of low plasma concentrations of NEFA and TG-rich lipoproteins. The of LPL in was to be of the LPL was markedly in of HSL-ko In LPL was induced in fasted mice in fed mice with LPL activity in the muscle and of fasted mice is expected to plasma TG in to the decreased VLDL synthesis in HSL-ko the tissue-specific LPL activity in cardiac muscle to be in the of TG-rich lipoproteins H. 1999; PubMed Scopus Google Scholar). LPL activity in is the total tissue LPL activity is the tissue is increased in mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google Scholar, J. L. L. Res. PubMed Scopus Google Scholar). is to that the total activity of the body is by the tissue-specific in cardiac muscle, skeletal muscle, and which are increased in fasted HSL-ko The for the coordinate of LPL in the or of HSL to be In AT, a of LPL and HSL was a of storage and mobilization K.N. Humphreys S.M. Adv. PubMed Scopus Google Scholar). coordinate of the tissue not of LPL activity in muscle and and of LPL in is a LPL levels were in these in HSL-ko and in LPL are a result of changes in enzyme or enzyme to the in the of LPL observed in in to and as and J. 1999; PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar). The that the induction of LPL in mice are several are the lack of induction of LPL in of HSL-ko mice in to a in is that the up-regulation of LPL is by the lipid stores in the as a the increased for fatty acids for lipid stores in H. M. PubMed Scopus Google Scholar, H. B. Holm C. PubMed Scopus Google Scholar). the decreased of fatty acids or a essential fatty from plasma or changes in the of HSL deficiency the of The is also with in to other LPL is in of that increased and lipid as observed in HSL-ko mice J. T. H. Kraemer F.B. 2000; PubMed Scopus Google LPL expression the The induction of LPL was in cardiac muscle, in with the that the heart is NEFA as the of cardiac muscle TG stores were decreased in HSL-ko The heart also the to of fatty acids as TG M. J. Biol. 266: Full Text PDF PubMed Google Scholar). TG is a fatty and fatty In fasted HSL-ko the cardiac TG was markedly an of fatty which was not by the up-regulation of the tissue LPL Decreased plasma TG levels as a result of decreased hepatic VLDL synthesis and increased VLDL are associated with increased plasma cholesterol and HDL cholesterol These are in with the that increased of TG-rich lipoproteins to the induction of LPL is an important of HDL cholesterol is generally that the lipolysis of and VLDL as that with hepatic are to by the of lipid and B. H. B. Biochim. Biophys. Acta. PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, 2000; PubMed Scopus Google Scholar, M. S.M. L.H. K. M. L. C. K. M. D. J. K. B. 1999; PubMed Scopus Google Scholar, M. J. T. C. M. K. C. 1999; PubMed Scopus Google Scholar, M. H. J. 1999; PubMed Scopus Google Scholar, 2000; PubMed Scopus Google Scholar). is to that the increased LPL in muscle and for the observed in HDL cholesterol In we that the changes observed in mice an important for the enzyme in the of lipid and lipoprotein