Down-regulation of Adipose Tissue Lipoprotein Lipase during Fasting Requires That a Gene, Separate from the Lipase Gene, Is Switched On

During short term fasting, lipoprotein lipase (LPL) activity in rat adipose tissue is rapidly down-regulated. This down-regulation occurs on a posttranslational level; it is not accompanied by changes in LPL mRNA or protein levels. The LPL activity can be restored within 4 h by refeeding. Previously, we showed that during fasting there is a shift in the distribution of lipase protein toward an inactive form with low heparin affinity. To study the nature of the regulatory mechanism, we determined the in vivo turnover of LPL activity, protein mass, and mRNA in rat adipose tissue. When protein synthesis was inhibited with cycloheximide, LPL activity and protein mass decreased rapidly and in parallel with half-lives of around 2 h, and the effect of refeeding was blocked. This indicates that maintaining high levels of LPL activity requires continuous synthesis of new enzyme protein. When transcription was inhibited by actinomycin, LPL mRNA decreased with half-lives of 13.3 and 16.8 h in the fed and fasted states, respectively, demonstrating slow turnover of the LPL transcript. Surprisingly, when actinomycin was given to fed rats, LPL activity was not down-regulated during fasting, indicating that actinomycin interferes with the transcription of a gene that blocks the activation of newly synthesized LPL protein. When actinomycin was given to fasted rats, LPL activity increased 4-fold within 6 h, even in the absence of refeeding. The same effect was seen with α-amanitin, another inhibitor of transcription. The response to actinomycin was much less pronounced in aging rats, which are obese and insulin-resistant. These data suggest a default state where LPL protein is synthesized on a relatively stable mRNA and is processed into its active form. During fasting, a gene is switched on whose product prevents the enzyme from becoming active even though synthesis of LPL protein continues unabated. During short term fasting, lipoprotein lipase (LPL) activity in rat adipose tissue is rapidly down-regulated. This down-regulation occurs on a posttranslational level; it is not accompanied by changes in LPL mRNA or protein levels. The LPL activity can be restored within 4 h by refeeding. Previously, we showed that during fasting there is a shift in the distribution of lipase protein toward an inactive form with low heparin affinity. To study the nature of the regulatory mechanism, we determined the in vivo turnover of LPL activity, protein mass, and mRNA in rat adipose tissue. When protein synthesis was inhibited with cycloheximide, LPL activity and protein mass decreased rapidly and in parallel with half-lives of around 2 h, and the effect of refeeding was blocked. This indicates that maintaining high levels of LPL activity requires continuous synthesis of new enzyme protein. When transcription was inhibited by actinomycin, LPL mRNA decreased with half-lives of 13.3 and 16.8 h in the fed and fasted states, respectively, demonstrating slow turnover of the LPL transcript. Surprisingly, when actinomycin was given to fed rats, LPL activity was not down-regulated during fasting, indicating that actinomycin interferes with the transcription of a gene that blocks the activation of newly synthesized LPL protein. When actinomycin was given to fasted rats, LPL activity increased 4-fold within 6 h, even in the absence of refeeding. The same effect was seen with α-amanitin, another inhibitor of transcription. The response to actinomycin was much less pronounced in aging rats, which are obese and insulin-resistant. These data suggest a default state where LPL protein is synthesized on a relatively stable mRNA and is processed into its active form. During fasting, a gene is switched on whose product prevents the enzyme from becoming active even though synthesis of LPL protein continues unabated. Lipoprotein lipase (LPL) 1The abbreviations used are: LPLlipoprotein lipase 1The abbreviations used are: LPLlipoprotein lipase plays an important physiological role in regulating the release of fatty acids from triglyceride-rich lipoproteins (1.Braun J.E.A. Severson D.L. Biochem. J. 1992; 287: 337-347Crossref PubMed Scopus (266) Google Scholar, 2.Eckel R.H. N. Engl. J. Med. 1989; 320: 1060-1068Crossref PubMed Scopus (851) Google Scholar, 3.Goldberg I.J. J. Lipid Res. 1996; 37: 693-707Abstract Full Text PDF PubMed Google Scholar, 4.Olivecrona T. Olivecrona G. Betteridge D.J. Illingworth D.R. Shepherd J. Lipoproteins in Health and Disease. Arnold, London1999: 223-246Google Scholar). The enzyme is synthesized in several extrahepatic tissues, but the highest activities are found in tissues that oxidize (e.g. heart and red skeletal muscle) or store (e.g. adipose tissue) fatty acids. After glycosylation, dimerization, and activation in the endoplasmic reticulum, the enzyme is secreted, transported through the extracellular matrix, and anchored to heparan sulfate proteoglycans on the intraluminal surface of nearby capillaries (3.Goldberg I.J. J. Lipid Res. 1996; 37: 693-707Abstract Full Text PDF PubMed Google Scholar,4.Olivecrona T. Olivecrona G. Betteridge D.J. Illingworth D.R. Shepherd J. Lipoproteins in Health and Disease. Arnold, London1999: 223-246Google Scholar). lipoprotein lipase lipoprotein lipase LPL is regulated at the level of gene expression in several physiological states: during fetal and early postnatal life, the enzyme is present in the liver but is then suppressed (5.Peinado-Onsurbe J. Staels B. Deeb S.S. Ramı́rez I. Llobera M. Auwerx J.H. Biochim. Biophys. Acta. 1992; 1131: 281-286Crossref PubMed Scopus (33) Google Scholar); in the mammary gland, the enzyme is switched on during lactation (6.McBride O.W. Korn E.D. J. Lipid Res. 1963; 4: 17-23Abstract Full Text PDF PubMed Google Scholar); in macrophages, it is switched on when the cells are activated (7.Auwerx J.H. Deeb S.S. Brunzell J.D. Peng R. Chait A. Biochemistry. 1988; 27: 2651-2655Crossref PubMed Scopus (98) Google Scholar); and in brown adipose tissue, the enzyme is switched on during cold adaptation (8.Carneheim C. Nedergaard J. Cannon B. Am. J. Physiol. 1988; 254: E155-E161PubMed Google Scholar). In white adipose tissue, LPL activity changes during the day according to the nutritional state. This appears to be mediated by posttranscriptional mechanisms. During short term fasting, LPL activity in rat adipose tissue decreases without corresponding changes in the levels of mRNA and protein mass, thereby reducing the specific activity (activity/protein mass ratio) (18.Doolittle M.H. Ben-Zeev O. Elovson J. Martin D. Kirchgessner T.G. J. Biol. Chem. 1990; 265: 4570-4577Abstract Full Text PDF PubMed Google Scholar, 20.Masuno H. Blanchette-Mackie E.J. Schultz C.J. Spaeth A.E. Scow R.O. Okuda H. J. Lipid Res. 1992; 33: 1343-1349Abstract Full Text PDF PubMed Google Scholar, 21.Park J.-W. Oh M.-S. Yang J.-Y. Park B.-H. Rho H.-W. Lim S.-N. Jhee E.-C. Kim H.-R. Biochim. Biophys. Acta Lipids Lipid Metab. 1995; 1254: 45-50Crossref PubMed Scopus (17) Google Scholar, 22.Masuno H. Blanchette-Mackie E.J. Chernick S.S. Scow R.O. J. Biol. Chem. 1990; 265: 1628-1638Abstract Full Text PDF PubMed Google Scholar). We have found that this occurs because the distribution of lipase protein shifts toward an inactive form (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar) and that refeeding for 4 h can restore the suppressed activity (10.Bergö M. Olivecrona G. Olivecrona T. Am. J. Physiol. Endocrinol. Metab. 1996; 271: E1092-E1097Crossref PubMed Google Scholar). The signal and mechanism for these changes in the activity status of the enzyme are unknown. To delineate the regulatory mechanism, we determined the turnover rates for LPL mRNA, mass, and activity in rat adipose tissue in the fed and fasted states and explored whether the regulation during feeding, fasting, and refeeding requires synthesis of new mRNA or protein. The results point to a novel mechanism and a new perspective on the nutritional regulation of LPL in adipose tissue. Male Sprague-Dawley rats (23 days old) weighing around 60 g were bought from Möllegaard Breeding Center (Ejby, Denmark). After transport to Umeå they were allowed to acclimatize for 7–10 days; during this time, they reached a weight of ∼120 g. The rats were kept in a well ventilated room at 21 °C and 40–50% humidity and had free access to standard laboratory chow (Laktamin AB, Stockholm, Sweden) and tap water. The light in the room was on between 6 a.m. and 6 p.m. In the fasting experiments, food was withdrawn from the cages at 6 a.m., and a grid was placed at the bottom of the cages to prevent coprophagia. In the refeeding experiments, the rats were put back on standard chow at 6 a.m. after a 24 h fast, and were killed at 12 noon by cervical dislocation. The adipose depot used in all experiments was periepididymal adipose tissue. The animal ethics committee in Umeå approved all animal experiments. Actinomycin-D, cycloheximide, bovine serum albumin, aprotinin (Trasylol), and HEPES were from Sigma. Leupeptin and pepstatin were from the Peptide Institute (Osaka, Japan). Heparin was from Lövens (Malmö, Sweden). The substrate for the LPL activity assay was 3H-labeled triolein in Intralipid (10%) from Amersham Biosciences, Inc. Parker medium (Parker 199) was from SBL (Stockholm, Sweden). All other reagents were of the highest commercial grade possible. Actinomycin and cycloheximide were dissolved in 0.9% NaCl (saline) and injected intraperitoneally at concentrations of 2 and 35 mg/kg body weight, respectively, The injected was LPL was from tissues by in a and (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar). The was for at after which the the and the for adipose tissue and the for other tissues was used for assay of LPL activity and LPL activity was (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar). 4 of tissue was for 60 at °C with substrate in the of of serum from fasted rats of and bovine serum The was After of the fatty acids were and for of lipase activity of fatty acids LPL was with a assay (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar). of tissue were in with was mediated the by a at was with a LPL mRNA was (10.Bergö M. Olivecrona G. Olivecrona T. Am. J. Physiol. Endocrinol. Metab. 1996; 271: E1092-E1097Crossref PubMed Google Scholar) with a assay from and Biochem. PubMed Scopus Google Scholar). LPL synthesized from a was for h with from rat adipose tissue. of were The were on and for The were with a standard and to the of in the was by by and C. Biochem. PubMed Scopus Google Scholar). and inactive of LPL in tissue were on (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar). The were with a and the were for LPL activity and lipase in rat was T. Olivecrona G. N. M.H. of Lipoprotein Scholar). The substrate was 3H-labeled triolein into an by LPL present in the was inhibited by a high were by of In the for was The for was used for 24 h LPL activity to of fed LPL protein mass decreased to After refeeding for 6 h, LPL activity had increased to of fed but LPL protein mass In rats that had given cycloheximide to protein LPL activity and protein mass refeeding These data that LPL protein is rapidly and that the of LPL during refeeding requires synthesis of new of nutritional state on LPL activity and mass in rat adipose tissue during of transcription of rats were fasted for 24 h from 6 a.m. the the or were fed 6 a.m. the rats were injected with cycloheximide or of the rats were for 6 h the 12 the rats were killed by and adipose tissue was and for LPL activity and mass and are from experiments and are in a new of rats were fasted for 24 h from 6 a.m. the the or were fed 6 a.m. the rats were injected with cycloheximide or of the rats were for 6 h the 12 the rats were killed by and adipose tissue was and for LPL activity and mass and are from experiments and are To the turnover of LPL we fed rats, which have high LPL activity in adipose tissue LPL activity and protein mass to 40–50% of within 2 h after the of cycloheximide and then decreased of at 6 These data that after the of protein synthesis by cycloheximide, the half-lives of LPL activity and protein mass in adipose tissue are less 2 h and that LPL activity decreases a of protein turnover and not because the enzyme protein its In these experiments, we used which mRNA When fasted rats were injected with actinomycin and then LPL activity increased to the same level in fed rats LPL protein mass not of LPL activity during refeeding not synthesis of new we determined whether down-regulation of LPL activity during fasting requires synthesis of new rats were injected with actinomycin or and food was from the cages h activity in adipose tissue from rats had to of fed Surprisingly, in adipose tissue from rats, activity was increased of These that the down-regulation of activity during fasting requires synthesis of new mRNA and suggest during fasting, a gene is switched on whose product prevents LPL from becoming active even though synthesis of LPL protein continues unabated. We that we injected actinomycin into fasted rats with low adipose tissue LPL activity, we this active LPL to be was 6 h after of actinomycin into fasted rats, LPL activity in adipose tissue had increased 4-fold without refeeding with in LPL protein These data that transcription with actinomycin the signal that of LPL activity on refeeding. To the that the in LPL activity by actinomycin be by a effect on the LPL protein by the actinomycin we experiments. we determined whether actinomycin LPL activity when to tissue in actinomycin was at concentrations of and to of adipose tissue from fasted rats assay of LPL activity or to the activity assay In of actinomycin had effect on LPL activity not we experiments with another inhibitor of of rats were fasted for 24 was given free access to food was injected with mg/kg body weight in and was injected with h the rats were and adipose tissue LPL activity and protein mass were activity in adipose tissue increased from in the fasted to in the on refeeding. In the LPL specific activity increased fasted data not These results that the effect of actinomycin on LPL activity in adipose tissue was not a it be with an inhibitor of Previously, we showed that after 24 h of fasting, LPL activity in adipose tissue is but the level of LPL mRNA the same in the fed after 60 h of fasting, the mRNA level decreases to less of fed (10.Bergö M. Olivecrona G. Olivecrona T. Am. J. Physiol. Endocrinol. Metab. 1996; 271: E1092-E1097Crossref PubMed Google Scholar). this the effect of refeeding is In the we whether the effect of actinomycin was after When rats were fasted for 60 h, LPL activity was of fed When these rats were given actinomycin, the in LPL activity after 6 h was to of the level in fed This indicates that the of the effect of actinomycin on adipose tissue LPL activity on the level of LPL of the that the used for actinomycin in vivo is 2 mg/kg body In a LPL activity in adipose tissue increased from injected with to with mg/kg 6 h after a of 2 LPL activity reached in the to 6 mg/kg not in an in LPL activity a of 2 mg/kg was used in experiments. LPL activity in adipose tissue of 24 h fasted rats was of that in fed rats 4 h after of actinomycin, the activity had increased to of fed and by 6 h the activity was restored was through h In this in the fed and fasted states and for h after actinomycin LPL protein mass not In a LPL mRNA was in the adipose tissue at and 24 h after actinomycin The level of LPL mRNA was and in fed and 24 h fasted rats, After of actinomycin the LPL mRNA level decreased The for the were and for the fed and fasted states, This to half-lives of 13.3 h and 16.8 h of LPL mRNA in adipose tissue from rats of and 24 h fasted rats were injected with and 24 h, or rats were killed by and adipose tissue was for of LPL mRNA and are LPL h after the of actinomycin to fasted rats, LPL activity increased and in and In and in which adipose tissue high levels of LPL activity increased and with These changes were not accompanied by changes in LPL The in LPL activity in adipose tissue and the in other tissues after actinomycin in a in LPL activity to the after a heparin LPL activity in increased were changes in lipase activity in liver or in not Previously, we showed that there are of LPL protein in tissues that can be by In the fasted the inactive form with low heparin the distribution of lipase protein shifts from the inactive toward the active form (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google which a high for To whether actinomycin had an effect to that of rats were fasted for 24 h and then injected with h adipose tissue were and and the LPL protein was on that in rats of the enzyme protein was in the which to the active in the fasted rats, the The between the were in the rats and in the fasted for the are and for fed and fasted rats, (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar). These data that LPL in adipose tissue from fasted rats injected with actinomycin is present in the active to LPL in adipose tissue from fed We have that the mechanism that LPL toward the inactive form on fasting is in adipose tissue from obese rats M. Olivecrona G. Olivecrona T. J. Metab. PubMed Scopus Google Scholar). actinomycin interferes with the same mechanism, its effect be in aging To this rats weighing 6 g were fasted for 24 h and then injected with actinomycin In response to actinomycin, LPL activity increased to of in 6 h This was in to the rats 2 where LPL activity was to of These data that the response of adipose tissue LPL to actinomycin is in aging This study that in fasting rats, a gene is switched on in adipose tissue that the tissue an inactive form of of mRNA synthesis by actinomycin the down-regulation of LPL activity in adipose tissue during of actinomycin or α-amanitin, another inhibitor of to fasted rats restored LPL activity within 6 for results is that actinomycin in vivo changes the levels of a or changes activity to the adipose tissue and that the effect on LPL activity is from the that this is not the In these actinomycin a in LPL activity in from fasted rats vivo Biochim. Biophys. Acta. PubMed Scopus Google Scholar, D.R. Biochem. J. PubMed Scopus Google Scholar). This indicates that the effect of actinomycin is a in the adipose tissue, to changes in or in have that and of the are important in the of LPL with high heparin (1.Braun J.E.A. Severson D.L. Biochem. J. 1992; 287: 337-347Crossref PubMed Scopus (266) Google H. Olivecrona T. J. Biol. Chem. 1989; Full Text PDF PubMed Google Scholar, M.H. Ben-Zeev O. Elovson J. Martin D. Kirchgessner T.G. J. Biol. Chem. 1990; 265: 4570-4577Abstract Full Text PDF PubMed Google Scholar, O. M.H. Elovson J. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar, 20.Masuno H. Blanchette-Mackie E.J. Schultz C.J. Spaeth A.E. Scow R.O. Okuda H. J. Lipid Res. 1992; 33: 1343-1349Abstract Full Text PDF PubMed Google Scholar, 21.Park J.-W. Oh M.-S. Yang J.-Y. Park B.-H. Rho H.-W. Lim S.-N. Jhee E.-C. Kim H.-R. Biochim. Biophys. Acta Lipids Lipid Metab. 1995; 1254: 45-50Crossref PubMed Scopus (17) Google Scholar). the of by in the endoplasmic to be a for the of activity O. M.H. Elovson J. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar, 20.Masuno H. Blanchette-Mackie E.J. Schultz C.J. Spaeth A.E. Scow R.O. Okuda H. J. Lipid Res. 1992; 33: 1343-1349Abstract Full Text PDF PubMed Google Scholar, 21.Park J.-W. Oh M.-S. Yang J.-Y. Park B.-H. Rho H.-W. Lim S.-N. Jhee E.-C. Kim H.-R. Biochim. Biophys. Acta Lipids Lipid Metab. 1995; 1254: 45-50Crossref PubMed Scopus (17) Google Scholar). that have processed in the have that are to by the enzyme showed that the form of the LPL protein in adipose tissue of fed rats, the form in adipose tissue of fasted rats (18.Doolittle M.H. Ben-Zeev O. Elovson J. Martin D. Kirchgessner T.G. J. Biol. Chem. 1990; 265: 4570-4577Abstract Full Text PDF PubMed Google Scholar). We have found that the active form of on is to the inactive form is G. T. and T. These data suggest that the mechanism for down-regulation of LPL during fasting the or of newly synthesized in the endoplasmic or early for a specific mechanism for of the enzyme from on by the lipase LPL in from these is in the endoplasmic in an inactive form with that are to H. Blanchette-Mackie E.J. Chernick S.S. Scow R.O. J. Biol. Chem. 1990; 265: 1628-1638Abstract Full Text PDF PubMed Google Scholar, Ben-Zeev O. A. M.H. J. Lipid Res. Full Text Full Text PDF PubMed Google Scholar). is that this is to the mechanism that LPL on cycloheximide to protein we the turnover of the LPL LPL activity and mass in adipose tissue from fed and fasted rats decreased rapidly and in with a of less 2 This that turnover of LPL activity is with turnover of LPL protein. are for this LPL protein be within the adipose tissue or the enzyme be transported with for in the liver Llobera M. G. Olivecrona T. Am. J. Physiol. 1988; 254: Google Scholar, T. G. H. G. Biochim. Biophys. Acta. 1988; PubMed Scopus Google Scholar). The turnover of LPL mRNA to During term fasting the to be 24 h in white adipose tissue (10.Bergö M. Olivecrona G. Olivecrona T. Am. J. Physiol. Endocrinol. Metab. 1996; 271: E1092-E1097Crossref PubMed Google Scholar) and h in brown adipose tissue A. Kirchgessner T.G. Cannon B. Nedergaard J. Am. J. Physiol. 1992; Google Scholar). During weight in obese rats R.H. Am. J. Physiol. PubMed Google Scholar) and during in B. J. Lipid Res. 1992; 33: Full Text PDF PubMed Google LPL mRNA turnover was found to be In the present the of LPL mRNA was 13.3 h in the fed state. During cold adaptation in rat brown adipose tissue, LPL activity mediated by increased transcription of the LPL to a specific enzyme is that the turnover of LPL mRNA A. Kirchgessner T.G. Cannon B. Nedergaard J. Am. J. Physiol. 1992; Google Scholar). this mechanism in white adipose tissue can the of LPL mRNA G. Olivecrona T. Biochem. J. 1988; PubMed Scopus Google Scholar). this mechanism not to during fasting the turnover of LPL mRNA not 16.8 this mRNA was for continuous synthesis of LPL protein even after the had given a stable mRNA, it is not for the to rapidly LPL activity on a the regulation be mediated on the or posttranslational a effect on in adipose tissue by lipase activity and by LPL In an showed that the effect of on LPL in is mediated by a protein that to the LPL and blocks its G. D. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). This the whether the same protein the down-regulation of LPL activity on this were the effect of actinomycin on LPL activity be to the transcription of this protein. of that this is not the that the mechanism for down-regulation of LPL during short term fasting is posttranslational and that the levels of LPL protein (9.Bergö M. Olivecrona G. Olivecrona T. Biochem. J. 1996; 313: 893-898Crossref PubMed Scopus (109) Google Scholar, M.H. Ben-Zeev O. Elovson J. Martin D. Kirchgessner T.G. J. Biol. Chem. 1990; 265: 4570-4577Abstract Full Text PDF PubMed Google Scholar, 20.Masuno H. Blanchette-Mackie E.J. Schultz C.J. Spaeth A.E. Scow R.O. Okuda H. J. Lipid Res. 1992; 33: 1343-1349Abstract Full Text PDF PubMed Google Scholar, 22.Masuno H. Blanchette-Mackie E.J. Chernick S.S. Scow R.O. J. Biol. Chem. 1990; 265: 1628-1638Abstract Full Text PDF PubMed Google Scholar). a in LPL synthesis mediated the in LPL activity on fasting there have to be an in LPL The present study that this is not the the turnover of LPL protein was the same in the fed and in the fasted an in LPL activity in rat in the of actinomycin D.R. Biochem. J. PubMed Scopus Google Scholar). This effect was by by the LPL protein. We have that this occurs in The in LPL activity in adipose tissue after actinomycin was when rats were given which a in LPL protein This indicates that the protein is activated by actinomycin synthesis of its it is that a of LPL by a decreased to a in the of in the LPL The nutritional regulation of LPL in adipose tissue a default state by a LPL activity that can be after in this study suggest another perspective on the the default state is by a high LPL activity and mass synthesized from a stable mRNA where the newly synthesized LPL is processed into the active form. The enzyme is then and transported to nearby capillaries where it on This to in tissues that LPL heart and skeletal During of between or during LPL mRNA and protein mass LPL activity in adipose tissue can be suppressed by the of a gene product that newly synthesized LPL to be into an inactive form. or of actinomycin the expression of this active LPL to be is there a to LPL during The of adipose LPL on results in the of fatty acids that can be by the tissue or be into the in form. The between these in adipose tissue 1995; PubMed Scopus Google from after a to release into the during of the of the fatty the down-regulation of LPL during fasting the of that through the adipose tissue. to LPL to the of fatty acids seen in with or it to an increased of in adipose tissue. with this found that activity in adipose tissue during fasting was in obese in J. 1989; PubMed Scopus Google Scholar). in obese activity was to a suggest that this to a in that LPL activity in these was not down-regulated during the fasting this be to we have found in obese rats where activity to be down-regulated on fasting M. Olivecrona G. Olivecrona T. J. Metab. PubMed Scopus Google Scholar). This the that on and the gene that LPL activity in adipose tissue be in and We are to for