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At least 217 records · Page 12Linked to original sources
PubMed1998

Regulation of hormone-sensitive lipase expression by glucose in 3T3-F442A adipocytes.

Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in adipocyte lipolysis. We have studied the effect of glucose and long chain fatty acids on the HSL mRNA content of 3T3-F442A adipocytes. Exposure of the cells for 32 h to a medium without glucose led to a decrease by a factor of 2.5-3 in the HSL mRNA without a change in C/EBP alpha mRNA or triglyceride content of the adipocytes. The reduction in HSL mRNA level was accompanied by a decrease in HSL total activity. The effect of glucose exposure was observed after 24 h of exposure and was reversible. Treatment of the adipocytes with oleate did not affect HSL expression. These data show that glucose modulates HSL gene expression and hence could participate in the regulation of adipose tissue lipolysis.

3T3 Cells↗
PubMed2005

Investigation into the role of the hormone sensitive lipase -60C>G promoter variant in morbid obesity.

BACKGROUND: Hormone sensitive lipase (HSL) plays a central role in free fatty acid homeostasis in adipose tissue and in pancreatic beta-cells, where it contributes to the control of insulin secretion by generating long-chain fatty acids. AIM: We examined the frequency and association of the functional HSL promoter variant, -60C>G, in a German cohort of morbidly obese women (N=239) and men (N=55) and compared the frequency to a cohort of 199 blood donors, recruited from the same region. RESULTS: The rare allele frequency of -60C>G, in the obese individuals was significantly lower 0.031 (95% CI 0.02, 0.04), than that in the blood donors 0.061 (95% CI 0.04, 0.08) p=0.05. The association of the HSL -60C>G with lipid and glucose parameters was examined in the obese women (there were too few men for comparative analysis). In the obese women, those heterozygous for the -60G had significantly higher glucose levels compared to CC women, 142.71 (+/-16.23) mg/dl vs. 110.34 (+/-1.79) mg/dl, respectively (p=0.0001). There was no statistically significant difference in other parameters. CONCLUSION: This study confirms a role for HSL in glucose homeostasis and the reduced frequency of the low expressing -60G promoter variant in obese individuals, together with existing published data, suggests that this allele might be protective against obesity.

Adult↗
PubMed2002

The hormone-sensitive lipase i6 gene polymorphism and body fat accumulation.

BACKGROUND: The hormone sensitive lipase (HSL) catalyses the breakdown of adipose tissue triglycerides into free fatty acids. The objective of this study was to determine whether HSLi6 microsatellite allele 5 (A5) and/or homozygosity for this allele is associated with body fat in Swedes. DESIGN: A large case-control study on gender-specific association for several body fat-related clinical parameters to HSLi6 A5, and to HSLi6 A5 homozygosity, comparing A5 with the other alleles in group. The subjects were 323 obese patients (85 males, 238 females) without other metabolic complication, and 301 nonobese healthy individuals (134 males, 167 females). They were analyzed for various body fat-related clinical parameters, and HSLi6 genotype. RESULTS: Homozygosity for HSLi6 A5 was a risk factor for obesity, BMI > or = 30 kg m-2 (Odds ratio = 1.75, 95% CI 1.58-1.93) and body fat mass > 39.6% (Odds ratio = 1.89, 95% CI 1.60-2.23) in women. This genotype was also associated with increased diastolic blood pressure and triglyceride level among nonobese women, and with increased body fat mass and waist/hip ratio among nonobese men. CONCLUSION: HSLi6 A5 homozygosity is a risk factor for body fat accumulation.

Adult↗
PubMed2004

Absence of hormone-sensitive lipase inhibits obesity and adipogenesis in Lep ob/ob mice.

Hormone-sensitive lipase (HSL) plays a crucial role in the hydrolysis of triacylglycerol and cholesteryl ester in various tissues including adipose tissues. To explore the role of HSL in the metabolism of fat and carbohydrate, we have generated mice lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) by cross-breeding HSL(-/-) mice with genetically obese Lep(ob/ob) mice. Unexpectedly, Lep(ob/ob)/HSL(-/-) mice ate less food, gained less weight, and had lower adiposity than Lep(ob/ob)/HSL(+/+) mice. Lep(ob/ob)/HSL(-/-) mice had massive accumulation of preadipocytes in white adipose tissues with increased expression of preadipocyte-specific genes (CAAT/enhancer-binding protein beta and adipose differentiation-related protein) and decreased expression of genes characteristic of mature adipocytes (CCAAT/enhancer-binding protein alpha, peroxisome proliferator activator receptor gamma, and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1). Consistent with the reduced food intake, hypothalamic expression of neuropeptide Y and agouti-related peptide was decreased. Since HSL is expressed in hypothalamus, we speculate that defective generation of free fatty acids in the hypothalamus due to the absence of HSL mediates the altered expression of these orexigenic neuropeptides. Thus, deficiency of both leptin and HSL has unmasked novel roles of HSL in adipogenesis as well as in feeding behavior.

Adipocytes↗
PubMed2004

Effects of reduced free fatty acid availability on hormone-sensitive lipase activity in human skeletal muscle during aerobic exercise.

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerol (IMTG); however, its regulation in skeletal muscle is poorly understood. To examine the effects of reduced free fatty acid (FFA) availability on HSL activity in skeletal muscle during aerobic exercise, 11 trained men exercised at 55% maximal O2 uptake for 40 min after the ingestion of nicotinic acid (NA) or nothing (control). Muscle biopsies were taken at rest and 5, 20, and 40 min of exercise. Plasma FFA were suppressed (P < 0.05) in NA during exercise ( approximately 0.40 +/- 0.04 vs. approximately 0.07 +/- 0.01 mM). The respiratory exchange ratio (RER) was increased throughout exercise (0.020 + 0.008) after NA ingestion. However, the provision of energy from fat oxidation only decreased from 33% of the total in the control trial to 26% in the NA trial, suggesting increased IMTG oxidation in the NA trial. Mean HSL activity was 2.25 + 0.15 mmol x kg dry mass(-1) x min(-1) at rest and increased (P < 0.05) to 2.94 +/- 0.20 mmol x kg dry mass(-1) x min(-1) at 5 min in control. Contrary to the hypothesis, mean HSL was not activated to a greater extent in the NA trial during exercise (2.20 + 0.28 at rest to 2.88 + 0.21 mmol x kg dry mass(-1) x min(-1) at 5 min). No further HSL increases were observed at 20 or 40 min in both trials. There was variability in the response to NA ingestion, as some subjects experienced a large increase in RER and decrease in fat oxidation, whereas other subjects experienced no shift in RER and maintained fat oxidation despite the reduced FFA availability in the NA trial. However, even in these subjects, HSL activity was not further increased during the NA trial. In conclusion, reduced plasma FFA availability accompanied by increased epinephrine concentration did not further activate HSL beyond exercise alone.

Adult↗
PubMed1997

Evidence for hormone-sensitive lipase mRNA expression in human monocyte/macrophages.

The role of hormone-sensitive lipase (HSL) in the hydrolysis of adipose tissue triacylglycerol to provide free fatty acids for energy requirements has been well established. However, the role of HSL in other tissues, including macrophages, is not well understood. The demonstration that HSL is capable of hydrolyzing cholesteryl esters at approximately the same rate as triacylglycerol raised the possibility that HSL activity in macrophages may influence the accumulation of cholesteryl esters in foam cells of atherosclerotic lesions. We and others have previously demonstrated that HSL mRNA is expressed in murine peritoneal macrophages and macrophage cell lines; however, it was previously reported that HSL mRNA is absent in human monocyte-derived macrophages, suggesting that a species difference may exist. To clarify this point, we have further examined the issue of HSL mRNA expression in human macrophages. In the current study, we demonstrate that HSL mRNA is detectable in human monocyte-derived macrophages and in the THP-1 human monocyte cell line using reverse transcription coupled to polymerase chain reaction (RT-PCR). Specific amplification of cDNA derived from mRNA was ensured by using primers that span an intron within the human HSL gene, and the identity of PCR products as HSL was confirmed by hybridization to HSL cDNA and by DNA sequencing. Using a semiquantitative PCR assay, we establish that HSL mRNA levels in monocyte/macrophages are approximately 1/40 the levels in human adipose tissue. These results indicate that further studies addressing the role of HSL in macrophage metabolism and its potential role in development of foam cells in human atherosclerotic lesions are warranted.

Adipose Tissue↗
PubMed1989

p-nitrophenyl butyrate hydrolyzing activity of hormone-sensitive lipase from bovine adipose tissue.

The "esterase" activity of hormone-sensitive lipase (HSL) was studied using water-soluble p-nitrophenyl butyrate (PNPB) as a substrate. Bovine adipose tissue HSL was purified to near homogeneity by precipitation at pH 5.0, followed by chromatography on DEAE-cellulose, phenyl-Sepharose, and high performance ion-exchange columns on Mono Q and Mono S. The purified preparation hydrolyzed emulsified triolein and cholesteryl oleate (CO), and water-soluble PNPB. In the two last steps of purification, the elution profile of the CO-hydrolyzing activity coincided with that of PNPB-hydrolyzing activity. The HSL was adsorbed to heparin-Sepharose and the CO- and PNPB-hydrolyzing activities were eluted together in the same peak. Diisopropylfluorophosphate (DFP) strongly inhibited the HSL activities and the inhibition profiles of the triolein-; CO-, and PNPB-hydrolyzing activities were essentially identical. Only one polypeptide of Mr 84,000 in partial purified HSL fraction was labeled by affinity labeling with [3H]DFP. On digestion of the enzyme with trypsin, the triolein- and CO-hydrolyzing activities were lost more rapidly than the PNPB-hydrolyzing activity. Phosphorylation increased the triolein-hydrolyzing activity to 40% more than that of the control, but did not affect the CO- and PNPB-hydrolyzing activities.

Adipose Tissue↗
PubMed2000

Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells.

Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.

Adipocytes↗
PubMed1982

Net calcium fluxes in rat parotid acinar cells: evidence for a hormone-sensitive calcium pool in or near the plasma membrane.

The effects of receptor stimulation on net fluxes of 45Ca in parotid acinar cells were investigated. When cellular 45Ca content was near steady-state, muscarinic receptor activation by carbachol caused a net efflux of 45Ca (not always reproducible) followed by a net influx. In the presence of excess ethylene glycol bis (beta-aminoethyl ether) N,N,N,N-tetraacetic acid, net efflux invariably occurred, but the influx phase was prevented. When the muscarinic receptor antagonist atropine was added to the medium during the influx phase, an abrupt transient influx occurred followed by a return of net influx to the prestimulation level. When cellular responses believed to reflect intracellular ionized Ca (k + permeability, protein secretion) were examined under similar conditions, atropine invariably had an inhibitory effect. The Ca taken up in response to atropine apparently replenishes the hormone-sensitive pool of cellular Ca since it can be released subsequently by adrenoceptor activation. Taken together, these observations suggest that when atropine is administered to cholinergically activated cells, the hormone-sensitive Ca pool rapidly refills from the extracellular fluid without a concomitant increase in ionized intracellular Ca. Thus, it is suggested that this Ca pool is most likely associated with the plasma membrane.

Animals↗
PubMed1987

Regulation of bovine adipose tissue metabolism during lactation. 3. Adaptations of hormone-sensitive and lipoprotein lipases.

Activity of lipases in adipose tissue during pregnancy and lactation was investigated in Holstein cows producing 5950 to 10,000 kg milk per 305 d. Activity of cytoplasmic lipoprotein lipase per gram of tissue was 97, 78, 140, 162, 179, and 235% of 30 d prepartum at -15, 15, 30, 60, 180, and 349 d about calving in yr 1. In yr 2, lipoprotein lipase per gram was 100, 259, 838, 791, and 430% of -30 d at -15, 30, 60, 120, and 180 d. Adaptations in activity per milligram cytoplasm protein were similar to those per gram tissue. Hormone-sensitive lipase per milligram protein was 161, 251, 114, 126, and 252% of -30 d when measured at 30, 60, 120, 180, and 240 d postpartum. Activity per gram of tissue responded similarly to the lactation state. Lipoprotein lipase is thus not a large contributor to the peripartum bovine adipose adaptation but is important in reattainment of body composition in mid and late lactation. Hormone-sensitive lipase is also increased during peak and midlactation. The pattern of elevated activity of these oppositely directed lipases reflects the dichotomous forces of milk fat production and body fat recovery acting on adipose tissue of lactating heifers.

Adipose Tissue↗
PubMed1993

Increased expression of the mRNA for hormone-sensitive lipase in adipose tissue of cancer patients.

The expression of genes coding for regulatory enzymes involved in the uptake, synthesis and mobilisation of lipid was measured in adipose tissue of cancer patients. Total RNA was isolated from subcutaneous adipose tissue of control and cancer patients and the various mRNAs measured by Northern blot analysis. The total lipoprotein lipase enzymic activity and the relative levels of the mRNAs for lipoprotein lipase and for fatty acid synthase were not significantly different between cancer patients and control patients. However, there was a significant two-fold increase in the relative level of mRNA for hormone-sensitive lipase (HSL) in adipose tissue of cancer patients compared with control patients. The cancer patients also exhibited a two-fold elevation in serum triacylglycerol levels and serum free fatty acid levels. There was a significant correlation between the serum free fatty acid level and expression of HSL mRNA in the adipose tissue. The serum levels of insulin and tumour necrosis factor-alpha were not different between cancer and control patients. The results suggest that at least one of the mechanisms for depletion of lipid from adipose tissue in cancer patients operates at the level of increased expression of mRNA of the lipolytic regulatory enzyme, hormone-sensitive lipase.

Adipose Tissue↗
PubMed2002

Effects of dynamic exercise intensity on the activation of hormone-sensitive lipase in human skeletal muscle.

It has been proposed that hormone-sensitive lipase (HSL) regulates intramuscular triacylglycerol hydrolysis in skeletal muscle. The primary purpose of this study was to examine the early activation of HSL and the changes in the putative intramuscular and hormonal regulators of HSL activity at various aerobic exercise intensities. Eight male subjects cycled for 10 min at power outputs corresponding to 30, 60 and 90 % peak oxygen uptake (VO(2,peak)). Muscle samples were obtained at rest and following 1 and 10 min of exercise. Intramuscular triacylglycerol (mean +/- S.E.M.: 24.3 +/- 2.3 mmol (kg dry mass (DM))(-1)), long-chain fatty acyl CoA (13.9 +/- 1.4 micromol (kg DM)(-1)) and HSL activity (1.87 +/- 0.07 mmol min(-1) (kg DM)(-1))) were not different between trials at rest. HSL activity increased at 1 min of exercise at 30 and 60 % VO(2,peak), and to a greater extent at 90 % VO(2,peak). HSL activity remained elevated after 10 min of exercise at 30 and 60 % VO(2,peak), and decreased at 90 % VO(2,peak) from the rates observed at 1 min (1 min: 3.41 +/- 0.3 mmol min(-1) (kg DM)-1; 10 min: 2.92 +/- 0.26 mmol min(-1) (kg DM)(-1)), P < 0.05). There were no effects of exercise power output or time on long-chain fatty acyl CoA content. At 90 % VO(2,peak), skeletal muscle contents of ATP and phosphocreatine were decreased (P < 0.05), and free ADP and free AMP were increased (P < 0.05) during exercise. No changes in these metabolites occurred at 30 % VO(2,peak) and only modest changes were observed at 60 % VO(2,peak). Plasma adrenaline increased (P < 0.05) during exercise at 90 % VO(2,peak) only. These data suggest that a factor related to the onset of exercise (e.g. Ca2+) activates HSL early in exercise. Given the activation of HSL early in exercise, at a time when intramuscular triacylglycerol hydrolysis and fat oxidation are considered to be negligible, we propose that the control of intramuscular triacylglycerol hydrolysis is not solely related to the level of HSL activation, but must also be regulated by postactivational factors.

Adenosine Triphosphate↗
PubMed1997

Hormone-sensitive lipase (Lipe): sequence analysis of the 129Sv mouse Lipe gene.

Hormone-sensitive lipase (Lipe) catalyzes both the release lease of fatty acids from storage triglycerides in adipocytes and the liberation of cholesterol from cholesterol esters in steroidogenic tissues. Lipe activity is regulated in a tissue-, development- and hormone-specific fashion, the latter in large part by serine phosphorylation. We cloned and sequenced the Lipe gene from the 129Sv strain mouse, including 2.7 kb of the 5' nontranslated region. The primary transcript of the 129Sv Lipe locus spans 9.6 kb and contains 9 exons. We studied the curious hypervariable region immediately 5' to the regulatory serine residues by aligning the peptide and nucleic acid sequences of mouse, human, and rat Lipe. We propose that much of the variability is attributable to differences in the copy number of a 12-nucleotide repeat that shifts the intron 7 acceptor splice site. Introns 1 and 7 contain B1 elements, which in intron 7 are immediately adjacent to a tetranucleotide repeat. The mouse Lipe promoter region contains numerous potential binding motifs for factors implicated in adipose tissue expression and hormone responsiveness including adipocyte determination- and differentiation-dependent factor 1 (ADD1/SREBP1).

Amino Acid Sequence↗
PubMed1981

Hormone-sensitive lipase in differentiated 3T3-L1 cells and its activation by cyclic AMP-dependent protein kinase.

Differentiation of 3T3-L1 fibroblasts to adipocyte-like cells was accompanied by a 19-fold increase in neutral triglyceride lipase activity, a 12-fold increase in diglyceride lipase activity, a 10-fold increase in monoglyceride lipase activity, and a 280-fold increase in cholesterol esterase activity. In contrast, acid acylhydrolase activities did not increase during differentiation. The rate of glycerol release from unstimulated intact cells increased by more than 1 order of magnitude upon differentiation. Isoproterenol (1 microM) and 1-methyl-3-isobutylxanthine (0.1 mM) further stimulated this rate of glycerol release 3-fold. The neutral triglyceride lipase activity in cell-free preparations of differentiated cells was activated 105% by cyclic AMP-dependent protein kinase. Neutral cholesterol esterase, diglyceride lipase, and monoglyceride lipase were also activated (117%, 10%, and 37+, respectively) by cyclic AMP-dependent protein kinase. In contrast, protein kinase had no effect on any of the four lysosomal acid acylhydrolase activities. Thus, hormone-sensitive lipase, the most characteristic and functionally important enzyme of adipose tissue, has been characterized in differentiated 3T3-L1 cells. The 3T3-L1 cell should be a valuable model system in which to study regulation of hormone-sensitive lipase, particularly its long-term regulation.

Adipose Tissue↗
PubMed1978

[Response to an antiestrogen as a criterion for hormonal sensitivity of endometrial cancer].

A test is described for the evaluation of hormone sensitivity of endometrial cancer in vivo. The concentrations of progesterone and estradiol receptors, and the activities of ornithine-decarboxylase and 17 beta-hydroxysteroid oxido-reductase enzymes have been measured in the tumor, before and after administration of the anti-estrogen tamoxifen. The responses observed, in particular the increase of progesterone receptor, could allow a more rational approach to hormonal therapy of endometrial cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1990

Incorporation of hormone-sensitive lipase into phosphatidylcholine vesicles.

Enzymatically active, detergent-solubilized purified hormone-sensitive lipase (HSL) was incorporated into phosphatidylcholine (PC) vesicles, using a detergent-dialysis procedure with small PC vesicles, obtained by sonication, as phospholipid source and CHAPS, a zwitterionic bile-salt derivative, as detergent. Association of enzyme protein with the PC vesicles was verified by floatation in a discontinuous dextran gradient and by gel chromatography. An average of 35% of added HSL was incorporated into the vesicles. The vesicles were shown, by quasi-elastic light scattering and electron microscopy, to have a diameter of approximately 160 nm. The vesicle-associated HSL could be phosphorylated by cyclic AMP-dependent protein kinase. The vesicles were stable, both with regard to enzyme activity and size, for at least 4 days when stored at 4 degrees C. The preparation of detergent-free, vesicle-associated and stable HSL provides new possibilities to study some of its properties, and supports and extends the previous report (Holm, C., Fredrikson, G., and Belfrage, P., J. Biol. Chem. 261, 15659-15661, 1986) which demonstrated the amphiphilic character of HSL.

Animals↗
PubMed1999

The porcine hormone-sensitive lipase gene: sequence, structure, polymorphisms and linkage mapping.

The porcine hormone-sensitive lipase gene and its cDNA have been isolated and sequenced. Several putative regulatory sequences have been detected in the promotor region. The deduced amino acid sequence is 85% identical to the corresponding human, mouse and rat sequence. A search for polymorphisms revealed one intronic and one exonic polymorphism, the latter resulting in a conservative amino acid substitution. Linkage mapping located the LIPE gene close to the calcium release channel (CRC) locus on chromosome 6.

Amino Acid Sequence↗
PubMed1992

Chromosomal localization of the hormone sensitive lipase (LIPE) and insulin receptor (INSR) genes in pigs.

Using rat hormone sensitive lipase (LIPE) and human insulin receptor (INSR) cDNA probes, the LIPE gene was assigned to chromosome 6p11-q21 and the INSR gene to chromosome 2q11-q21 in pigs by in situ hybridization. In humans, these two genes are located on the q and p arms of chromosome 19, respectively. The present results provide the first in situ hybridization mapping data for porcine chromosome 2.

Animals↗