Disease relevance of LIPE

• Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity [1].
• Subcutaneous HSL mRNA content was normalised upon weight reduction [2].
• C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor gamma expression in adipose tissue of familial combined hyperlipidemia patients [3].
• LPL and HSL activity was investigated in 10 nonobese FCHL patients and compared with 10 matched healthy nonobese subjects, and in 8 essentially normolipidemic IRS patients (who did not have overt diabetes mellitus) and compared with 9 nonobese matched control subjects [4].
• In obese subjects, adipose tissue HSL and LPL fail to respond to immunoreactive insulin postprandially, which may be an important maladaptation in terms of lipoprotein metabolism and risk of coronary heart disease [5].

Psychiatry related information on LIPE

• This study retrospectively investigated the effect of left (LHS) versus right (RHS) hippocampal sclerosis on verbal memory, measured by means of the Paired Associate Learning and Logical Memory subtests of the Wechsler Memory Scale (WMS) administered as part of a routine preoperative assessment [6].

High impact information on LIPE

• A flurry of research over the past decade has led to significant understanding of many aspects of quorum sensing including the synthesis of acyl-HSLs, the receptors that recognize the acyl-HSL signal and transduce this information to the level of gene expression, and the interaction of these receptors with the transcriptional machinery [7].
• Variations in the maximum lipolysis rate correlated significantly with the variations in hormone-sensitive lipase activity in the whole material, and with the serum values for triglycerides, HDL cholesterol and apoB lipoprotein within the control group, but the serum triglyceride values in FCHL were higher than this correlation predicted [8].
• In conclusion, a decreased activation of the hormone-sensitive lipase complex appears to be the mechanism underlying a blunted lipolytic response of fat cells to catecholamine stimulation in elderly subjects [9].
• (2003) provide convincing support to the notion that the subcellular compartmentalization of lipase also regulates lipolysis, and, more importantly, that proteins other than HSL are localized to the lipid droplet and are indispensable for its optimal hydrolysis [10].
• Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that functions as the rate-limiting enzyme for the mobilization of free fatty acids in adipose tissue [11].

Chemical compound and disease context of LIPE

• 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline [12].
• To this aim, 191 diabetic patients, all with type 2 diabetes, were randomized to either CR-LIPE or standard protein restriction and the following outcomes monitored: doubling of serum creatinine, cumulative incidence of end-stage renal disease, and all cause mortality [13].
• Therefore, we have examined two LIPE single nucleotide polymorphism (SNP) [14672C>G in the promoter region and 17948C>T (rs1206034) on intron 2] in relation to plasma lipids, anthropometrical and glucose-related phenotypes in a population of mostly overweight and obese men (373) and women (361) [14].
• Our randomized placebo-controlled study comprising 32 volunteers showed that aralox treatment led to a decrease in total body weight and fat weight, reduced perilipin content in adipocytes and plasma triglyceride content, and stimulated activity of hormone-sensitive lipase [15].
• VIP also increased cAMP generation in seven other human breast cancer cell lines: H4-66B, HSL 53, HSL 78, MCF 7, MDA-MB231, T-47D2, and ZR75-1 [16].

Biological context of LIPE

• Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene [17].
• CONCLUSION: These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent [17].
• RESULTS: There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene [17].
• Free fatty acids are the major source of fuel for mammals, and hormone sensitive lipase (LIPE) plays a critical role in lipid metabolism by mobilizing free fatty acids from stored triglycerides [18].
• Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.1-->q13.2 [18].

Anatomical context of LIPE

• Physical association between the adipocyte fatty acid-binding protein and hormone-sensitive lipase: a fluorescence resonance energy transfer analysis [19].
• RESULTS: Obesity was associated with a decreased subcutaneous and increased omental adipose tissue level of HSL mRNA [2].
• HSL and ATGL cDNAs were transfected into Cos-7 cells and the relative tri- and diglyceride hydrolase activities were measured [2].
• After correction for percent body fat, only HSL and C3 mRNA levels remained significantly different between groups (P < 0.05) [20].
• Therefore, it is important to elucidate the regulation of HSL activity in human skeletal muscle during exercise [21].

Associations of LIPE with chemical compounds

• In the presence of 20 microm forskolin, CFP-HSL translocated to the triacylglycerol droplet, coincident with BODIPY-FA labeled depots [19].
• The pH profile of human white adipose tissue triolein hydrolase activity was identical to that of HSL but differed from the ATGL profile [2].
• The highest concentration of E(2) also significantly increased both HSL expression and glycerol release relative to control [22].
• No difference in steady-state mRNA expression level of C3, HSL, or PPARgamma mRNA was detected between the FCHL patients and the control subjects [3].
• The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase [23].

Physical interactions of LIPE

• HSL has been shown to interact with adipocyte lipid-binding protein (ALBP), a member of the family of intracellular lipid-binding proteins that bind fatty acids and other hydrophobic ligands [24].
• In the plasma membrane PTRF was specifically bound to a triacylglycerol-metabolizing subclass of caveolae containing hormone-sensitive lipase (HSL) [25].

Enzymatic interactions of LIPE

• In conclusion, the present study suggests that AMPK phosphorylates HSL on Ser565 in human skeletal muscle during exercise with reduced muscle glycogen [21].

Regulatory relationships of LIPE

• Anti-E 10(-8) mol/L alone reduced LPL protein expression relative to control (P <.05) and increased HSL protein expression relative to control (P >.05) [22].
• In the current study, we tested the capacity of 5'AMP-activated protein kinase (AMPK) to suppress beta-adrenergic stimulation of HSL activity [26].
• Peroxisome proliferator-activated receptor-gamma transcriptionally up-regulates hormone-sensitive lipase via the involvement of specificity protein-1 [27].
• Transgenic mice were produced with a 21 kb human genomic fragment encompassing the exons encoding the adipocyte form of HSL. hHSL mRNA was expressed at 3-fold higher levels than murine HSL mRNA in white adipocytes [28].
• The effect of interleukin-1 and interleukin-2 on the adrenergic control of hormone-sensitive lipase in the human adipocyte [29].

Other interactions of LIPE

• To assess AFABP-HSL interaction within a cellular context, we have used lipocytes derived from 293 cells (C8PA cells) and examined physical association using fluorescence resonance energy transfer [19].
• A high adipose tissue lipase activity was associated with increased maximal lipolysis and increased HSL, but not with ATGL mRNA levels [2].
• However, HSL, C3, and PPAR gamma mRNA levels were higher in middle-aged than in young individuals (P < 0.01-0.05) [20].
• In women HSL mRNA expression decreased by 31% (P=0.008) and LPL expression increased slightly, but nonsignificantly (42%, P=0.110) [30].
• Fluorescence resonance energy transfer analysis demonstrated that CFP-HSL associated with YFP-adipocyte FABP in both basal and forskolin-treated cells [19].

Analytical, diagnostic and therapeutic context of LIPE

• Direct sequence analysis of a 1 kb segment of cosmid 26710 identifies a dinucleotide repeat in an intron upstream of exon 8 of human LIPE [18].
• HSL mRNA level was positively correlated with waist-to-hip ratio in patients, whereas the correlation was negative in control subjects [3].
• Renal replacement therapy or death occurred in 18 patients on CR-LIPE (20%) and in 31 control subjects (39%) (P < 0.01) [13].
• Site-directed mutagenesis of the HSL promoter showed that the GC-boxes, although contributing to basal promoter activity, were dispensable for glucose responsiveness [31].
• The mRNA of various adipocyte markers was detected by reverse transcriptase-polymerase chain reaction analysis, including hormone-sensitive lipase, lipoprotein lipase, adipsin, glucose transporters 1 and 4, the uncoupling protein (specific of brown adipocytes), and leptin, the product of the ob gene [32].

References