Affinage

LIPE

Hormone-sensitive lipase · UniProt Q05469

Length
1076 aa
Mass
116.6 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIPE encodes hormone-sensitive lipase (HSL), an intracellular neutral lipase that mobilizes stored neutral lipids across adipose, steroidogenic, muscle, macrophage, germ-cell, and retinal tissues by hydrolyzing diacylglycerols, cholesteryl esters, and retinyl esters (PMID:8496671, PMID:19246492, PMID:20625037). HSL is a head-to-head homodimer present as multiple tissue-specific isoforms that share this architecture and PKA-dependent activation (PMID:20567594). Its activity is acutely gated by reversible phosphorylation: PKA phosphorylates activating sites including Ser563 and Ser660, while AMPK phosphorylates the inhibitory Ser565, allowing AMPK to override beta-adrenergic stimulation of lipolysis in a tissue-dependent manner (PMID:15231718, PMID:16188906); a serine-to-alanine mutation at the homologous regulatory residue markedly impairs in vivo rescue of HSL function (PMID:15961788). A second inhibitory input comes from PAK4, which directly phosphorylates HSL at Ser565 to impair its interaction with FABP4, an action relieved when PKA targets PAK4 for degradation (PMID:38216738). Beyond phosphorylation, HSL action is controlled by regulated translocation to lipid droplets upon lipolytic stimulation (PMID:16905768), where access is governed by a Perilipin1–HSL interface that ApoL6 blocks by binding Perilipin1, and is promoted by DECR1, which enhances HSL phosphorylation and droplet recruitment (PMID:34896618, PMID:38167864). LIPE transcription is driven by PKA/SF-1 signaling in steroidogenic cells and by the PPARgamma/RXRalpha heterodimer in adipose tissue (PMID:17134676, PMID:21081692). Physiologically, HSL is required for male fertility through cholesteryl ester hydrolysis in postmeiotic germ cells (PMID:15292223, PMID:15345679), for retinoid mobilization and maintenance of circulating retinol/RBP4 (PMID:19246492, PMID:38769419), and for retinal lipid homeostasis (PMID:37198396); its loss or dysregulation contributes to lipodystrophy through biallelic LIPE null variants in humans (PMID:33112291), to liposarcoma in combination with ATGL deficiency (PMID:28459858, PMID:31035700), and to cancer cell lipid metabolism and migration via a KRAS–HSL axis (PMID:32816911).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1993 High

    Established HSL as a hormonally regulated intracellular neutral lipase, defining the core enzymatic identity and the link between catecholamine signaling and its phosphorylation.

    Evidence Recombinant HSL expression, antibody-based immunoprecipitation of 32P-labeled HSL from adipocytes, and cholesterol esterase immunodepletion across tissues

    PMID:8496671

    Open questions at the time
    • Specific activating phosphosites not yet mapped
    • Substrate preference among TG, DG, and CE not quantified
  2. 1998 Medium

    Extended HSL function to skeletal muscle and revealed a contraction-driven activation pathway operating independently of beta-adrenergic/PKA signaling.

    Evidence In vitro incubation of rat muscle with epinephrine and beta-blockers, electrical stimulation, and antiserum-neutralized lipase activity assays

    PMID:9781328

    Open questions at the time
    • Molecular identity of the PKA-independent activator unknown
    • Single-lab pharmacological dissection
  3. 2004 High

    Resolved the activating versus inhibitory phosphosite logic, showing PKA activates via Ser563/Ser660 while AMPK inhibits via Ser565 and can override beta-adrenergic stimulation in a tissue-specific way.

    Evidence Human exercise biopsies, phospho-specific Western blotting, AMPK activity assays, and CA-AMPK/AICAR in L6 myotubes and 3T3-L1 adipocytes

    PMID:15231718 PMID:16188906

    Open questions at the time
    • Structural basis for differential tissue Ser660 maintenance not defined
    • Phosphatase counter-regulation not characterized
  4. 2005 High

    Demonstrated by site-specific mutagenesis and in vivo rescue that a regulatory serine is functionally required for normal HSL lipolytic activity.

    Evidence Transgenic WT vs S554A human HSL on HSL-/- background with WAT mass, histology, DG content, and lipolysis readouts

    PMID:15961788

    Open questions at the time
    • Mechanism by which the residue affects catalysis or localization not resolved
  5. 2006 High

    Identified regulated translocation to lipid droplets as a distinct layer of HSL control beyond phosphorylation.

    Evidence Confocal and EM imaging of rat muscle fibers showing HSL movement to ADRP-associated droplets after epinephrine or contraction

    PMID:16905768

    Open questions at the time
    • Targeting determinants on HSL not mapped
    • Relationship between phosphorylation and translocation not dissected
  6. 2004 High

    Defined an essential, cell-autonomous role for testicular HSL in postmeiotic germ cells, linking its cholesteryl ester hydrolase activity to male fertility.

    Evidence Dose-dependent transgenic rescue of HSL-null mice with HSLtes or postmeiotic-specific human testicular HSL, with CE hydrolase, histology, and fertility readouts

    PMID:15292223 PMID:15345679

    Open questions at the time
    • Downstream cholesterol metabolites driving spermatid maturation not identified
  7. 2009 High

    Expanded the substrate repertoire by identifying HSL as a retinyl ester hydrolase, connecting it to retinoic acid signaling and adipocyte differentiation.

    Evidence In vitro REH assay with recombinant HSL plus LC/MS/MS retinoid quantification and RA rescue in HSL-null mice

    PMID:19246492

    Open questions at the time
    • Tissue-specific contribution of REH versus other hydrolases not quantified
  8. 2010 High

    Established HSL as the dominant macrophage neutral cholesteryl ester hydrolase governing cAMP-dependent cholesterol efflux, while revealing cooperating enzymes.

    Evidence HSL-/- macrophage lipase activity assays across CE/TG/DG substrates and cholesterol efflux measurements

    PMID:20625037

    Open questions at the time
    • Identity of cooperating CE hydrolases not fully defined
  9. 2010 High

    Defined HSL quaternary structure as a head-to-head homodimer shared across isoforms, providing a structural framework for its conserved enzymology.

    Evidence Negative-stain EM of purified isoforms with psychrotolerance and PKA activation assays

    PMID:20567594

    Open questions at the time
    • High-resolution catalytic and regulatory domain structure not determined
  10. 2011 Medium

    Mapped transcriptional control of LIPE to PPARgamma/RXRalpha in adipose tissue and to PKA/SF-1 in steroidogenic cells.

    Evidence Luciferase reporter, ChIP, and EMSA for PPRE binding; reporter, siRNA, and H89 dissection of SF-1-driven promoter A in adrenocortical cells

    PMID:17134676 PMID:21081692 PMID:26122391

    Open questions at the time
    • Single-lab promoter studies
    • Crosstalk between adipose and steroidogenic promoters not integrated
  11. 2017 High

    Revealed genetic redundancy and epistasis between HSL and ATGL, with combined loss causing liposarcoma and ATGL acting as a transacylase in HSL absence.

    Evidence Adipose double-knockout mice, lipase and radiolabeled DG transacylase assays, Atglistatin, and histopathology

    PMID:28459858 PMID:31035700

    Open questions at the time
    • Mechanism linking lipase loss to tumorigenesis not defined
  12. 2020 High

    Placed HSL downstream of KRAS in pancreatic cancer, linking lipid droplet utilization and oxidative metabolism to tumor cell migration and metastasis.

    Evidence KRAS and HSL gain/loss-of-function in PDAC lines, lipid droplet imaging, invasion assays, and in vivo metastasis models

    PMID:32816911

    Open questions at the time
    • Direct transcriptional mechanism of KRAS control of HSL not resolved
  13. 2021 Medium

    Identified DECR1 as a direct HSL partner that promotes its phosphorylation and droplet translocation, enhancing lipolysis in cancer cells.

    Evidence Co-IP, DECR1 overexpression/silencing, phospho-HSL Western blotting, and FFA/TG assays in HeLa cells

    PMID:34896618

    Open questions at the time
    • Single-lab Co-IP
    • Whether interaction is direct or kinase-mediated not fully resolved
  14. 2023 High

    Established HSL as essential for retinal and RPE lipid homeostasis, with loss causing retinal degeneration and abnormal retinal lipid profiles.

    Evidence CRISPR Lipe-/- mice with fundus imaging, histology, ERG, and retinal lipidomics

    PMID:37198396

    Open questions at the time
    • Causal lipid species driving degeneration not pinpointed
  15. 2024 High

    Defined the lipid-droplet gating machinery, showing ApoL6 forms a Perilipin1–HSL complex that blocks Perilipin1 from binding HSL to suppress lipolysis.

    Evidence Reciprocal Co-IP, domain mapping, and ApoL6 gain/loss in adipocytes and diet-induced obesity mice

    PMID:38167864

    Open questions at the time
    • How phosphorylation state modulates the ApoL6/Plin1/HSL complex not resolved
  16. 2024 High

    Added PAK4 as a direct Ser565 kinase inhibiting HSL via disrupted FABP4 binding, itself degraded by PKA, integrating a kinase-degradation switch into lipolytic control.

    Evidence In vitro kinase assay, adipose-specific PAK4 KO/overexpression mice, FABP4-HSL Co-IP, and lipolysis/obesity readouts

    PMID:38216738

    Open questions at the time
    • Interplay between PAK4 and AMPK at Ser565 not dissected
  17. 2024 High

    Connected adipocyte HSL to systemic retinoid homeostasis, showing it is required for fasting circulating retinol/RBP4 and apo-RBP4-induced retinol release.

    Evidence Global and adipocyte-specific HSL KO mice, serum retinol/RBP4, apo-RBP4 stimulation, and retinoid-responsive gene profiling

    PMID:38769419

    Open questions at the time
    • Molecular coupling of REH activity to retinol export not defined
  18. 2024 Medium

    Implicated LIPE in alpha-synuclein pathology, with reduced LIPE attenuating motor deficits via decreased MUFA release into membranes that alpha-synuclein engages.

    Evidence LIPE null cross with 3K alpha-synuclein mice, motor testing, alpha-synuclein biochemistry, lipid profiling, and neurotransmitter measurement

    PMID:38971480

    Open questions at the time
    • Single-lab study
    • Basis of male-specific benefit unknown
    • Direct neuronal HSL activity not measured
  19. 2021 Medium

    Linked biallelic LIPE loss-of-function to human lipodystrophy phenotypes with defective lipolysis, insulin response, and mitochondrial function.

    Evidence Patient-derived adipose stem cells with biallelic null variants, REH assays in HSL-null mice, and differentiation/lipolysis/insulin/mitochondrial assays

    PMID:33112291

    Open questions at the time
    • Single-center patient cohort
    • Mechanism connecting HSL loss to mitochondrial dysfunction not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs—PKA/AMPK/PAK4 phosphorylation, droplet translocation, and the ApoL6/Plin1/DECR1/FABP4 protein network—are integrated into a unified spatiotemporal control of HSL substrate access remains unresolved.
  • No integrated structural model of regulated HSL at the droplet surface
  • Quantitative hierarchy of activating vs inhibitory inputs unknown
  • Tissue-specific isoform regulatory differences not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4
Localization
GO:0005811 lipid droplet 3 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3
Partners
APOL6DECR1FABP4PAK4PLIN1
Complex memberships
ApoL6–Perilipin1–HSL lipid droplet complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 HSL is an intracellular neutral lipase expressed in adipose, steroidogenic, and other tissues (adrenal, testis, heart, lung) that hydrolyzes triglycerides and cholesteryl esters; phosphorylation of the 84 kDa adipocyte HSL is stimulated ~4-fold by isoproterenol as shown by 32P-labeling and immunoprecipitation. Recombinant HSL/fusion protein expression in E. coli, generation of polyclonal antibodies, immunoprecipitation of 32P-labeled HSL from adipocytes, cholesterol esterase activity immunodepletion assays Journal of lipid research High 8496671
1998 HSL is expressed in skeletal muscle fibers and its neutral lipase activity is increased by epinephrine via beta-adrenergic/cAMP/PKA mechanisms, and independently by electrical stimulation (contraction); the stimulation by contractions is not abolished by sympathectomy or propranolol, indicating a PKA-independent contraction pathway also activates HSL. Western blotting of isolated rat muscle fibers, in vitro incubation of soleus muscle with epinephrine and beta-blockers, electrical stimulation, neutral lipase activity assay with labeled substrate, anti-HSL antiserum neutralization Advances in experimental medicine and biology Medium 9781328
2004 HSL in skeletal muscle is phosphorylated and activated by the beta-adrenergic/cAMP/PKA pathway; AMPK alpha-2 activation (enhanced by low glycogen exercise) can override beta-adrenergic stimulation of HSL activity, confirmed in L6 myotubes by AICAR treatment. Human exercise trials with skeletal muscle biopsies, HSL activity assays, phospho-specific Western blotting (Ser563, Ser660, Ser565), AMPK activity assays, AICAR treatment of L6 myotubes FASEB journal High 15231718
2005 HSL is regulated by PKA-dependent phosphorylation at Ser563 and Ser660 (activating) and AMPK-dependent phosphorylation at Ser565 (inhibitory/regulatory). In skeletal muscle, AMPK activation after epinephrine stimulation reduces HSL Ser660 phosphorylation and activity, whereas in adipose tissue HSL Ser660 is maintained despite AMPK activation, preserving lipolytic activity. Human exercise biopsy studies, phospho-specific Western blotting (Ser563, Ser660, Ser565), HSL activity assays, constitutively active AMPK expression in L6 myotubes, AICAR treatment of 3T3-L1 adipocytes American journal of physiology. Endocrinology and metabolism High 16188906
2005 Expression of normal human HSL in white adipose tissue of HSL-/- mice rescues WAT mass, histology, diacylglycerol content, and beta-adrenergic lipolytic response; a serine-to-alanine mutant (S554A) at similar expression levels has markedly lower physiological rescue, indicating S554 is functionally important for normal HSL activity in vivo. Transgenic mice expressing wild-type or S554A human HSL in WAT on HSL-/- background; WAT mass, histology, diacylglyceride content, and lipolytic response to beta-adrenergic agents measured Journal of lipid research High 15961788
2006 Upon epinephrine stimulation or muscle contraction, HSL translocates from the cytoplasm to intramuscular lipid droplets (associated with ADRP), coinciding with a decrease in intramuscular triglyceride content; translocation is a key regulatory mechanism of HSL activity in skeletal muscle. Confocal and transmission electron microscopy of rat soleus single muscle fibers after epinephrine incubation or electrical stimulation; immunofluorescence co-localization of HSL with ADRP/TIP47 Journal of lipid research High 16905768
2004 The testis-specific HSL isoform HSLtes is expressed in elongated spermatids and its cholesteryl ester hydrolase activity in testis is essential for male fertility; transgenic re-expression of HSLtes in HSL-null mice fully restores spermatogenesis and fertility in a dose-dependent manner correlated with cholesteryl ester hydrolase activity. Transgenic mice expressing HSLtes under its own promoter crossed to HSL-/- background; cholesteryl ester hydrolase activity assays, testicular histology, sperm counts, fertility assessment The Journal of biological chemistry High 15292223
2004 HSL expression specifically in postmeiotic germ cells is sufficient to restore normal fertility in HSL-/- male mice, demonstrating that the infertility mechanism of HSL deficiency is cell-autonomous and resides in postmeiotic germ cells; HSL restores testicular cholesteryl esterase activity and normalizes the esterified/free cholesterol ratio. Transgenic mice expressing human testicular HSL cDNA from the protamine-1 promoter (postmeiotic-specific) on HSL-/- background; cholesteryl esterase activity assay, testicular mass, cholesterol ratio, histology, fertility Endocrinology High 15345679
2009 HSL functions as a retinyl ester hydrolase (REH) with higher activity against retinyl palmitate than against its canonical substrate diacylglycerol; HSL-null mice show complete loss of REH activity in white adipose tissue, accumulation of retinyl esters, and decreased retinoic acid signaling, affecting adipocyte differentiation and lineage commitment. In vitro REH assay with recombinant HSL and retinyl palmitate; LC/MS/MS quantification of retinoids in HSL-null vs WT mice WAT; qPCR of RA-regulated genes; dietary RA rescue experiment FASEB journal High 19246492
2010 HSL is the predominant neutral cholesteryl ester hydrolase in macrophages; HSL-/- macrophages show near-complete loss of neutral CE hydrolase activity, and cAMP-dependent cholesterol efflux is dependent on HSL, while CE accumulation remains similar to WT, indicating additional enzymes cooperate with HSL in regulating macrophage CE levels. Macrophages from HSL-/- and KIAA1363-/- mice; fluorometric lipase activity assays with CE, TG, DG, AcMAGE substrates; cholesterol efflux assays; CE turnover measurement Journal of lipid research High 20625037
2010 HSL quaternary structure is a head-to-head homodimer where each monomer contains two structural domains; all three isoforms (84, 89, 117 kDa) share this architecture. All isoforms exhibit similar enzymological properties including cold adaptation (psychrotolerance) and PKA-mediated phosphorylation and activation. Negative stain electron microscopy of purified HSL isoforms; enzymatic activity assays for psychrotolerance; PKA phosphorylation and activation assays PloS one High 20567594
2011 HSL transcription is regulated by the PPARgamma/RXRalpha heterodimer via a functional PPRE in the HSL promoter, as demonstrated by reporter assays with deletion and point mutants, ChIP showing PPARgamma and RXRalpha binding to the promoter region, and EMSA confirming heterodimer binding. Reporter assay (luciferase) with serial deletion and point mutants of HSL 5'-flanking region in CV-1 cells; ChIP with PPARgamma and RXRalpha antibodies; EMSA Biochemical and biophysical research communications Medium 17134676
2011 ACTH activates LIPE gene transcription via the PKA pathway in adrenocortical cells; PKA stimulation increases SF-1 expression, which then activates LIPE transcription by binding SF-1 response elements in LIPE promoter A; SF-1 siRNA knockdown abolishes PKA-stimulated LIPE transcription. Luciferase reporter assay with LIPE promoter constructs in H295R cells; RT-PCR and Western blotting for LIPE mRNA and protein; siRNA knockdown of SF-1; PKA inhibitor H89 treatment Journal of molecular endocrinology Medium 21081692
2015 SF-1 is essential for PKA-induced LIPE expression in adrenocortical Y-1 cells; SF-1 expression itself is induced by PKA signaling, and SF-1 activates LIPE promoter A transcription via SF-1 response elements; simultaneous PKA and PKC activation reduces SF-1 expression, suppressing LIPE induction. PKA and PKC pathway stimulation/inhibition in Y-1 cells; luciferase reporter assay with LIPE promoter A; SF-1 siRNA; RT-PCR and Western blotting Molecular and cellular biochemistry Medium 26122391
2017 Combined adipose-specific knockout of both ATGL (Pnpla2) and HSL (Lipe) causes fully penetrant liposarcoma in mice by 11-14 months; single knockouts show no tumors. HSL also exhibits intrinsic TG hydrolase activity, and ATGL functions as a transacylase when HSL is absent (transferring acyl groups from DG to form TG), revealing a previously unknown epistatic interaction and functional redundancy between the two lipases. Double adipose knockout (DAKO) mice; lipase activity assays; radiolabeled DG incubation with HSL-deficient lipid droplet fractions; specific ATGL inhibitor (Atglistatin); transcriptome analysis; histopathology PLoS genetics / Cells High 28459858 31035700
2020 KRAS controls HSL expression in pancreatic cancer (PDAC) cells; HSL is downregulated in human PDAC. Disruption of the KRAS-HSL axis reduces lipid droplet utilization, reprograms tumor cell metabolism away from oxidative phosphorylation, and inhibits invasive migration in vitro and metastasis in vivo; migratory cells selectively utilize oxidative metabolism to mobilize stored lipids via HSL. KRAS knockdown/activation in PDAC cell lines; HSL knockdown/overexpression; lipid droplet imaging; in vitro invasion assays; in vivo metastasis models; microscopy-based metabolic analysis Cancer research High 32816911
2021 DECR1 directly interacts with HSL, and this interaction increases HSL phosphorylation and activity, facilitating HSL translocation to lipid droplets and enhancing lipolysis and free fatty acid release in cervical cancer cells. Co-immunoprecipitation (DECR1-HSL interaction); DECR1 overexpression and silencing; Western blotting for phospho-HSL; confocal microscopy of HSL localization; triglyceride content and FFA release assays in HeLa cells Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 34896618
2024 ApoL6, a lipid droplet-associated protein, inhibits lipolysis by forming a complex with Perilipin1 (Plin1) and HSL on lipid droplets; C-terminal ApoL6 directly interacts with N-terminal Plin1 to prevent Plin1 from binding HSL, thereby blocking HSL-mediated lipolysis. Co-immunoprecipitation (ApoL6, Plin1, HSL); ApoL6 knockdown and overexpression in adipocytes; lipid droplet size/TAG content measurement; diet-induced obesity model in ApoL6-ablated vs overexpressing mice Nature communications High 38167864
2024 PAK4 directly phosphorylates HSL at S565, impairing its interaction with FABP4 and inhibiting lipolysis; PKA targets PAK4 for degradation, thereby relieving PAK4-mediated suppression of HSL; adipose-specific PAK4 knockout or PAK4 inhibitor treatment enhances lipolysis and ameliorates diet-induced obesity. In vitro kinase assay (PAK4 phosphorylation of HSL-S565); adipose-specific PAK4 knockout and overexpression mice; Co-IP (FABP4-HSL interaction); phospho-specific Western blotting; lipolysis assays; diet-induced obesity model Nature metabolism High 38216738
2024 Adipocyte HSL is required for maintaining circulating retinol and RBP4 levels during fasting; extracellular apo-RBP4 induces retinol release from adipocytes in an HSL-dependent manner. Global or adipocyte-specific HSL deficiency causes retinoid accumulation in adipose tissue and a drop in serum retinol/RBP4, affecting retinoid-responsive gene expression in eye and kidney. Global and adipocyte-specific HSL knockout mice; serum retinol and RBP4 quantification; apo-RBP4 stimulation of adipocytes; retinoid tissue profiling; retinoid-responsive gene expression (RT-PCR) EMBO reports High 38769419
2023 Lipe (LIPE) is essential for retinal and RPE lipid homeostasis; Lipe-/- mice develop subretinal microglial accumulation, retinal degeneration with decreased visual function, and an abnormal retinal lipid profile, establishing HSL as a key enzyme in maintaining retinal lipid balance. Forward genetic screen; CRISPR-Cas9-generated Lipe-/- mice; fundus imaging; retinal histology; electroretinography; lipidomic profiling of retina Communications biology High 37198396
2024 Reducing LIPE expression (heterozygous knockout) in a mouse model of alpha-synuclein aggregation (3K mice) attenuates motor deficits, improves the alpha-synuclein tetramer-to-monomer ratio, and restores dopaminergic neurotransmitter levels and fiber densities; the mechanism involves decreased MUFA release from neutral lipid storage, reducing MUFA incorporation into phospholipid membranes with which alpha-synuclein interacts. Sex differences were observed: benefits were seen in males but not females. Genetic cross of LIPE null mice with 3K alpha-synuclein mice; motor behavior testing; alpha-synuclein biochemistry (T:M ratio, pS129); lipid profiling; dopamine/neurotransmitter measurement; fiber density immunohistochemistry Neurobiology of disease Medium 38971480
2000 Masoprocol decreases HSL lipolytic activity by inhibiting PKA-dependent phosphorylation of HSL, an effect that can be blocked by the serine/threonine phosphatase inhibitor okadaic acid, suggesting masoprocol activates a phosphatase that dephosphorylates HSL. Isoproterenol-stimulated lipolysis and HSL activity assays in isolated rat adipocytes; 32P-phosphorylation assay; okadaic acid rescue experiment; PI3-kinase activity assay American journal of physiology. Endocrinology and metabolism Medium 10950827
2012 In HSL-knockout testis, class B scavenger receptors (SR-BI, SR-BII, LIMP II) are upregulated, caveolin-1 localization in lipid raft microdomains is disrupted, and ERK, AKT, and SRC phosphorylation are activated, indicating HSL-mediated cholesteryl ester hydrolysis is required for normal lipid raft composition and downstream signaling during spermatogenesis. HSL-KO mouse testis; immunofluorescence localization of SR-B receptors; lipid raft fractionation; Western blotting for phospho-ERK, phospho-AKT, phospho-SRC, caveolin-1; sperm count and motility assays Journal of lipid research Medium 22988039
2021 HSL-null mice completely lack retinyl ester hydrolase (REH) activity in white adipose tissue (confirmed with a loss-of-function model), and loss of HSL impairs adipocyte differentiation as shown by decreased expression of adipogenic markers in patient-derived adipose stem cells with biallelic LIPE null variants; LIPE-mutated cells also display defective lipolysis, decreased insulin response, and mitochondrial dysfunction. Patient-derived adipose stem cells (ASCs) from lipomatous tissue with biallelic LIPE null variants; immunohistology of lipomatous tissue; adipocyte differentiation assays; lipolysis assays; insulin response assays; mitochondrial function assays European journal of endocrinology Medium 33112291

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis. Bioorganic & medicinal chemistry letters 229 19500981
2010 Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. American journal of physiology. Cell physiology 219 20107043
2005 Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. American journal of physiology. Endocrinology and metabolism 197 16188906
2008 Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. Journal of lipid research 164 19050316
2003 Biofilm formation by Pseudomonas aeruginosa: role of the C4-HSL cell-to-cell signal and inhibition by azithromycin. The Journal of antimicrobial chemotherapy 151 12951348
2003 Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice. American journal of physiology. Endocrinology and metabolism 133 12954598
2020 KRAS Controls Pancreatic Cancer Cell Lipid Metabolism and Invasive Potential through the Lipase HSL. Cancer research 132 32816911
2011 The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis. Gene 131 21241784
2012 Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues. Molecular & cellular proteomics : MCP 97 22984285
2006 Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. Journal of lipid research 82 16905768
1993 Detection of hormone-sensitive lipase in various tissues. I. Expression of an HSL/bacterial fusion protein and generation of anti-HSL antibodies. Journal of lipid research 78 8496671
2022 An Overview of Hormone-Sensitive Lipase (HSL). TheScientificWorldJournal 77 36530555
2004 Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle. American journal of physiology. Endocrinology and metabolism 77 14749208
2009 Hormone-sensitive lipase (HSL) is also a retinyl ester hydrolase: evidence from mice lacking HSL. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 71 19246492
2004 Beta-adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 15231718
2005 Role of the N terminus in enzyme activity, stability and specificity in thermophilic esterases belonging to the HSL family. Journal of molecular biology 63 15581894
2002 The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue. Diabetes, obesity & metabolism 63 12047400
2004 Expression and characterization of the protein Rv1399c from Mycobacterium tuberculosis. A novel carboxyl esterase structurally related to the HSL family. European journal of biochemistry 62 15373841
2014 A novel LIPE nonsense mutation found using exome sequencing in siblings with late-onset familial partial lipodystrophy. The Canadian journal of cardiology 60 25475467
2006 The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) enhances the host defence by activating human polymorphonuclear neutrophils (PMN). Analytical and bioanalytical chemistry 58 16906383
2001 Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression. American journal of physiology. Endocrinology and metabolism 48 11551864
2016 Homozygous LIPE mutation in siblings with multiple symmetric lipomatosis, partial lipodystrophy, and myopathy. American journal of medical genetics. Part A 47 27862896
2010 Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363. Journal of lipid research 44 20625037
1998 Hormone-sensitive lipase (HSL) expression and regulation in skeletal muscle. Advances in experimental medicine and biology 44 9781328
2023 Membrane Protein Amuc_1100 Derived from Akkermansia muciniphila Facilitates Lipolysis and Browning via Activating the AC3/PKA/HSL Pathway. Microbiology spectrum 42 36847500
2009 Chronic TNFalpha and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis. FEBS letters 40 19695247
2017 Epistatic interaction between the lipase-encoding genes Pnpla2 and Lipe causes liposarcoma in mice. PLoS genetics 37 28459858
2004 Analysis of thermal adaptation in the HSL enzyme family. Journal of molecular biology 36 14659763
2022 Distinct AMPK-Mediated FAS/HSL Pathway Is Implicated in the Alleviating Effect of Nuciferine on Obesity and Hepatic Steatosis in HFD-Fed Mice. Nutrients 35 35565866
1994 Precise localization of the genes for glucose phosphate isomerase (GPI), calcium release channel (CRC), hormone-sensitive lipase (LIPE), and growth hormone (GH) in pigs, using nonradioactive in situ hybridization. Cytogenetics and cell genetics 33 8062599
2021 LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells. European journal of endocrinology 31 33112291
2019 Update on the synergistic effect of HSL and insulin in the treatment of metabolic disorders. Therapeutic advances in endocrinology and metabolism 31 31565213
2012 Fat-reducing effects of dehydroepiandrosterone involve upregulation of ATGL and HSL expression, and stimulation of lipolysis in adipose tissue. Steroids 31 22951290
2024 ApoL6 associates with lipid droplets and disrupts Perilipin1-HSL interaction to inhibit lipolysis. Nature communications 30 38167864
2019 Priming winter wheat seeds with the bacterial quorum sensing signal N-hexanoyl-L-homoserine lactone (C6-HSL) shows potential to improve plant growth and seed yield. PloS one 28 30802259
2018 Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 29439250
2017 Furvina inhibits the 3-oxo-C12-HSL-based quorum sensing system of Pseudomonas aeruginosa and QS-dependent phenotypes. Biofouling 28 28140677
2005 Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice. Journal of lipid research 28 15961788
1995 FISH on metaphase and interphase chromosomes demonstrates the physical order of the genes for GPI, CRC, and LIPE in pigs. Cytogenetics and cell genetics 28 7656591
2004 The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice. The Journal of biological chemistry 27 15292223
2024 p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL. Nature metabolism 26 38216738
2004 Expression of human hormone-sensitive lipase (HSL) in postmeiotic germ cells confers normal fertility to HSL-deficient mice. Endocrinology 26 15345679
2019 An Epistatic Interaction between Pnpla2 and Lipe Reveals New Pathways of Adipose Tissue Lipolysis. Cells 25 31035700
2007 Developmental changes of the FAS and HSL mRNA expression and their effects on the content of intramuscular fat in Kazak and Xinjiang sheep. Journal of genetics and genomics = Yi chuan xue bao 25 17945169
2006 Identification of peroxisome-proliferator responsive element in the mouse HSL gene. Biochemical and biophysical research communications 25 17134676
2020 Effect of salt promote the muscle triglyceride hydrolysis during dry-salting by inducing the phosphorylation of adipose tissue triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and lipid droplets splitting. Food chemistry 24 32454271
2009 The crystal structure of an HSL-homolog EstE5 complex with PMSF reveals a unique configuration that inhibits the nucleophile Ser144 in catalytic triads. Biochemical and biophysical research communications 24 19715665
1995 Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.1-->q13.2. Cytogenetics and cell genetics 24 7698015
2019 Effects of liraglutide on lipolysis and the AC3/PKA/HSL pathway. Diabetes, metabolic syndrome and obesity : targets and therapy 23 31564937
2016 Mechanism of azithromycin inhibition of HSL synthesis in Pseudomonas aeruginosa. Scientific reports 23 27075730
2012 HSL-knockout mouse testis exhibits class B scavenger receptor upregulation and disrupted lipid raft microdomains. Journal of lipid research 23 22988039
2022 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors. Scientific reports 22 35676403
2011 ATGL and HSL are not coordinately regulated in response to fuel partitioning in fasted rats. The Journal of nutritional biochemistry 22 20621463
2021 DECR1 directly activates HSL to promote lipolysis in cervical cancer cells. Biochimica et biophysica acta. Molecular and cell biology of lipids 21 34896618
2022 Label-Free Electrochemical Aptasensor for the Detection of the 3-O-C12-HSL Quorum-Sensing Molecule in Pseudomonas aeruginosa. Biosensors 20 35884243
2022 Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation. Journal of ethnopharmacology 20 36334816
2021 A Study of the Regulatory Mechanism of the CB1/PPARγ2/PLIN1/HSL Pathway for Fat Metabolism in Cattle. Frontiers in genetics 20 34017353
2017 Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a form of autophagy in 3T3-L1 adipocytes. Journal of cellular physiology 20 28488768
2012 Essential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages. Microbial pathogenesis 20 22553833
2012 Influence and mechanism of N-(3-oxooxtanoyl)-L-homoserine lactone (C8-oxo-HSL) on biofilm behaviors at early stage. Journal of environmental sciences (China) 20 23534198
2006 Adrenergic regulation of HSL serine phosphorylation and activity in human skeletal muscle during the onset of exercise. American journal of physiology. Regulatory, integrative and comparative physiology 20 16690773
2000 Free fatty acids are involved in the inverse relationship between hormone-sensitive lipase (HSL) activity and expression in adipose tissue after high-fat feeding or beta3-adrenergic stimulation. Obesity research 20 10832769
2021 Biochemical and Structural Characterization of a novel thermophilic esterase EstD11 provide catalytic insights for the HSL family. Computational and structural biotechnology journal 19 33680362
2010 Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle. Biochemical and biophysical research communications 19 20691154
2023 Sudachitin and Nobiletin Stimulate Lipolysis via Activation of the cAMP/PKA/HSL Pathway in 3T3-L1 Adipocytes. Foods (Basel, Switzerland) 18 37238764
2022 Role of lncRNA LIPE-AS1 in adipogenesis. Adipocyte 18 34957921
2000 NF-kappaB/p50 and NF-kappaB/c-Rel differentially regulate the activity of the 3'alphaE-hsl,2 enhancer in normal murine B cells in an activation-dependent manner. International immunology 18 10917891
2015 SF-1 (NR5A1) expression is stimulated by the PKA pathway and is essential for the PKA-induced activation of LIPE expression in Y-1 cells. Molecular and cellular biochemistry 17 26122391
2013 Piromelatine decreases triglyceride accumulation in insulin resistant 3T3-L1 adipocytes: role of ATGL and HSL. Biochimie 17 23707538
2011 Transcription of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase is regulated by SF-1 in human adrenocortical cells: involvement of protein kinase A signal transduction pathway. Journal of molecular endocrinology 17 21081692
1997 Hormone-sensitive lipase (Lipe): sequence analysis of the 129Sv mouse Lipe gene. Mammalian genome : official journal of the International Mammalian Genome Society 17 9060404
2019 Morbid obesity-related changes in the expression of lipid receptors, transporters, and HSL in human sperm. Journal of assisted reproduction and genetics 16 30659447
2019 C4-HSL aptamers for blocking qurom sensing and inhibiting biofilm formation in Pseudomonas aeruginosa and its structure prediction and analysis. PloS one 16 30779754
2021 C12-HSL is an across-boundary signal molecule that could alleviate fungi Galactomyces's filamentation: A new mechanism on activated sludge bulking. Environmental research 15 34400160
2013 Association of HSL gene E1-c.276C>T and E8-c.51C>T mutation with economical traits of Chinese Simmental cattle. Molecular biology reports 15 24213829
2005 A simple, rapid, sensitive method detecting homoserine lactone (HSL)-related compounds in microbial extracts. Journal of microbiological methods 15 16019090
2000 Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL. American journal of physiology. Endocrinology and metabolism 15 10950827
2023 Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity. Molecular metabolism 14 37935315
2023 Functionally conserved PPARG exonic circRNAs enhance intramuscular fat deposition by regulating PPARG and HSL. International journal of biological macromolecules 14 38070814
2023 C4-HSL-mediated quorum sensing regulates nitrogen removal in activated sludge process at Low temperatures. Environmental research 14 38128597
2014 Progesterone-induced down-regulation of hormone sensitive lipase (Lipe) and up-regulation of G0/G1 switch 2 (G0s2) genes expression in inguinal adipose tissue of female rats is reflected by diminished rate of lipolysis. The Journal of steroid biochemistry and molecular biology 14 25448749
2011 Relationship between site-specific HSL phosphorylation and adipocyte lipolysis in obese women. Obesity facts 14 22166756
2008 Cloning and functional characterization of the 5' regulatory region of ovine Hormone Sensitive Lipase (HSL) gene. Gene 13 18824087
2024 Follicular fluid-derived exosomal LncRNA LIPE-AS1 modulates steroid metabolism and survival of granulosa cells leading to oocyte maturation arrest in polycystic ovary syndrome. Journal of assisted reproduction and genetics 12 38656738
2024 Reducing the lipase LIPE in mutant α-synuclein mice improves Parkinson-like deficits and reveals sex differences in fatty acid metabolism. Neurobiology of disease 12 38971480
2014 Characterization of the bovine gene LIPE and possible influence on fatty acid composition of meat. Meta gene 12 25606458
2020 Human Single-chain Variable Fragments Neutralize Pseudomonas aeruginosa Quorum Sensing Molecule, 3O-C12-HSL, and Prevent Cells From the HSL-mediated Apoptosis. Frontiers in microbiology 11 32670218
2019 Bromodomain-containing protein 2 promotes lipolysis via ERK/HSL signalling pathway in white adipose tissue of mice. General and comparative endocrinology 11 31121164
2008 Cloning and functional characterization of the ovine Hormone Sensitive Lipase (HSL) full-length cDNAs: an integrated approach. Gene 11 18436396
2007 Characterization of N-butanoyl-L-homoserine lactone (C4-HSL) deficient clinical isolates of Pseudomonas aeruginosa. Microbial pathogenesis 11 17689222
2024 Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting. EMBO reports 10 38769419
2024 Effect of L-HSL on biofilm and motility of Pseudomonas aeruginosa and its mechanism. Applied microbiology and biotechnology 10 39012538
2020 The reduction of lipid-sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish. Fish physiology and biochemistry 10 33245450
2009 LIPE C-60G influences the effects of physical activity on body fat and plasma lipid concentrations: the Quebec Family Study. Human genomics 10 19164092
1992 Chromosomal localization of the hormone sensitive lipase (LIPE) and insulin receptor (INSR) genes in pigs. Hereditas 10 1295851
2023 Forward genetic screening using fundus spot scale identifies an essential role for Lipe in murine retinal homeostasis. Communications biology 9 37198396
2021 Promotion effect of salt on intramuscular neutral lipid hydrolysis during dry-salting process of porcine (biceps femoris) muscles by inducing phosphorylation of ATGL, HSL and their regulatory proteins of Perilipin1, ABHD5 and G0S2. Food chemistry 9 34815115
2010 Genetic variation at the goat hormone-sensitive lipase ( LIPE) gene and its association with milk yield and composition. The Journal of dairy research 9 20380772
2010 Quarternary structure and enzymological properties of the different hormone-sensitive lipase (HSL) isoforms. PloS one 9 20567594
1995 The hormone-sensitive lipase (LIPE) gene located on chromosome 19q13.1-->13.2 is not duplicated on 19p13.3. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 9 7489032

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