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ApoA5 lowers triglyceride levels via suppression of ANGPTL3/8-mediated LPL inhibition

Chen, Yan Q., Pottanat, Thomas G., Zhen, Eugene Y., Siegel, Robert W., Ehsani, Mariam, Qian, Yue-Wei, Konrad, Robert J.·2021·Journal of Lipid Research
DOI 10.1016/j.jlr.2021.100068PMC PMC8079461
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Fig. 1 ApoA5 associates with ANGPTL3/8 in human serum. A: The ANGPTL3/8 complex was coupled to beads that were incubated with human serum overnight at 4°C. Bound proteins were reduced, alkylated, and digested with trypsin. The means (from triplicate samples) of the areas under the curve (AUC) for peptide ions significantly different from control (P < 0.05 and fold-change > 5) were plotted in a scatter dot plot. Only ApoA5 peptide ions met these criteria. The AUC was extracted for each ion with a mass tolerance of 2 ppm. Results shown are representative of 3 independent experiments. B: To confirm the association of ApoA5 with ANGPTL3/8 in human serum, an irrelevant, negative control antibody, an anti-ANGPTL3 antibody, an anti-ANGPTL8 antibody, and an anti-ApoA5 antibody were covalently coupled to beads and used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated on gels and transferred to PVDF membranes. The blots were stained with an anti-ApoA5 antibody, an anti-ANGPTL3 antibody, or an anti-ANGPTL8 antibody. ANGPTL8, angiopoietin-like protein 8.
Fig. 1 ApoA5 associates with ANGPTL3/8 in human serum. A: The ANGPTL3/8 complex was coupled to beads that were incubated with human serum overnight at 4°C. Bound proteins were reduced, alkylated, and digested with trypsin. The means (from triplicate samples) of the areas under the curve (AUC) for peptide ions significantly different from control (P < 0.05 and fold-change > 5) were plotted in a scatter dot plot. Only ApoA5 peptide ions met these criteria. The AUC was extracted for each ion with a mass tolerance of 2 ppm. Results shown are representative of 3 independent experiments. B: To confirm the association of ApoA5 with ANGPTL3/8 in human serum, an irrelevant, negative control antibody, an anti-ANGPTL3 antibody, an anti-ANGPTL8 antibody, and an anti-ApoA5 antibody were covalently coupled to beads and used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated on gels and transferred to PVDF membranes. The blots were stained with an anti-ApoA5 antibody, an anti-ANGPTL3 antibody, or an anti-ANGPTL8 antibody. ANGPTL8, angiopoietin-like protein 8.CC BY · PubMed Central
Fig. 2 An anti-ANGPTL3/8-specific antibody immunoprecipitates ApoA5 from human serum. A: Biolayer interferometry confirmed the specific binding of the anti-ANGPTL3/8 antibody to ANGPTL3/8 and not free ANGPTL3 or ANGPTL8. B: The anti-ANGPTL3/8 antibody was used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated, transferred to PVDF, and stained with anti-ANGPTL3 antibody to confirm pull down of ANGPTL3. C: The anti-ANGPTL3/8-specific antibody was used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated, transferred to PVDF, and stained with anti-ANGPTL8 antibody to confirm pull down of ANGPTL8. D: An irrelevant, negative control antibody, the anti-ANGPTL3/8 antibody, and an anti-ApoA5 antibody were used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated, transferred to PVDF, and stained with the anti-ApoA5 antibody. Results are representative of two independent experiments. ANGPTL8, angiopoietin-like protein 8.
Fig. 2 An anti-ANGPTL3/8-specific antibody immunoprecipitates ApoA5 from human serum. A: Biolayer interferometry confirmed the specific binding of the anti-ANGPTL3/8 antibody to ANGPTL3/8 and not free ANGPTL3 or ANGPTL8. B: The anti-ANGPTL3/8 antibody was used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated, transferred to PVDF, and stained with anti-ANGPTL3 antibody to confirm pull down of ANGPTL3. C: The anti-ANGPTL3/8-specific antibody was used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated, transferred to PVDF, and stained with anti-ANGPTL8 antibody to confirm pull down of ANGPTL8. D: An irrelevant, negative control antibody, the anti-ANGPTL3/8 antibody, and an anti-ApoA5 antibody were used to immunoprecipitate human serum overnight at 4°C. Immunoprecipitated proteins were separated, transferred to PVDF, and stained with the anti-ApoA5 antibody. Results are representative of two independent experiments. ANGPTL8, angiopoietin-like protein 8.CC BY · PubMed Central
Fig. 3 Expression and purification of recombinant ApoA5 protein and characterization of its binding to the ANGPTL3/8 complex. A: Recombinant human ApoA5-HSA, HSA-ApoA5, and control HSA protein (0.5 μg of each) were analyzed either without or with PreScission cleavage of the HSA tag. Proteins were separated via gradient gel electrophoresis using a 4%–20% Tris-glycine gel and stained with Coomassie Blue. B: Biolayer interferometry was used to examine the binding affinity of ApoA5 to the ANGPTL3/8 complex. Flag-tagged ANGPTL3/8 complex was first immobilized on streptavidin biosensors coated with anti-Flag antibody. Immobilized ANGPTL3/8 was then incubated with increasing concentrations of ApoA5 (6.25–100 nM) to monitor association of ApoA5 with the ANGPTL3/8 complex and then transferred into buffer-only wells to monitor its dissociation from the ANGPTL3/8 complex, with background reference subtraction performed. ApoA5 binding to ANGPTL3/8 demonstrated a moderate on-rate (association) and a very slow off-rate (dissociation). Curves were fit globally using a 1:1 binding model to generate kon, koff, and KD values of 2.60 × 105 M−1s−1, 1.35 × 10−4 s−1, and 520 pM, respectively. Raw data were plotted in black and the curve fits in gray. Results are representative of three independent experiments. ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.
Fig. 3 Expression and purification of recombinant ApoA5 protein and characterization of its binding to the ANGPTL3/8 complex. A: Recombinant human ApoA5-HSA, HSA-ApoA5, and control HSA protein (0.5 μg of each) were analyzed either without or with PreScission cleavage of the HSA tag. Proteins were separated via gradient gel electrophoresis using a 4%–20% Tris-glycine gel and stained with Coomassie Blue. B: Biolayer interferometry was used to examine the binding affinity of ApoA5 to the ANGPTL3/8 complex. Flag-tagged ANGPTL3/8 complex was first immobilized on streptavidin biosensors coated with anti-Flag antibody. Immobilized ANGPTL3/8 was then incubated with increasing concentrations of ApoA5 (6.25–100 nM) to monitor association of ApoA5 with the ANGPTL3/8 complex and then transferred into buffer-only wells to monitor its dissociation from the ANGPTL3/8 complex, with background reference subtraction performed. ApoA5 binding to ANGPTL3/8 demonstrated a moderate on-rate (association) and a very slow off-rate (dissociation). Curves were fit globally using a 1:1 binding model to generate kon, koff, and KD values of 2.60 × 105 M−1s−1, 1.35 × 10−4 s−1, and 520 pM, respectively. Raw data were plotted in black and the curve fits in gray. Results are representative of three independent experiments. ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.CC BY · PubMed Central
Fig. 4 ApoA5 selectively blocks the ability of ANGPTL3/8 to inhibit LPL activity. The ability of ANGPTL3/8, ANGPTL4, ANGPTL3, and ANGPTL4/8 to inhibit the LPL activity in the presence of 0 nM (squares), 25 nM (triangles), 100 nM (diamonds), and 300 nM (circles) of ApoA5 (HSA-ApoA5) was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. All results are shown as the mean ± SD (n = 3 from three independent experiments). A: ANGPTL3/8 was preincubated with ApoA5 before the addition of lipase substrate. B: ANGPTL4 was preincubated with ApoA5 before the addition of lipase substrate. C: ANGPTL3 was preincubated with ApoA5 before the addition of lipase substrate. D: ANGPTL4/8 was preincubated with ApoA5 before the addition of lipase substrate. ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.
Fig. 4 ApoA5 selectively blocks the ability of ANGPTL3/8 to inhibit LPL activity. The ability of ANGPTL3/8, ANGPTL4, ANGPTL3, and ANGPTL4/8 to inhibit the LPL activity in the presence of 0 nM (squares), 25 nM (triangles), 100 nM (diamonds), and 300 nM (circles) of ApoA5 (HSA-ApoA5) was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. All results are shown as the mean ± SD (n = 3 from three independent experiments). A: ANGPTL3/8 was preincubated with ApoA5 before the addition of lipase substrate. B: ANGPTL4 was preincubated with ApoA5 before the addition of lipase substrate. C: ANGPTL3 was preincubated with ApoA5 before the addition of lipase substrate. D: ANGPTL4/8 was preincubated with ApoA5 before the addition of lipase substrate. ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.CC BY · PubMed Central
Fig. 5 HSA-ApoA5 and ApoA5-HSA block ANGPTL3/8-mediated LPL inhibitory activity in a similar manner to PreScission-cleaved HSA-ApoA5 and PreScission-cleaved ApoA5-HSA. A: The ability of 100 nM HSA-ApoA5 (diamonds) and 100 nM ApoA5-HSA (circles) to inhibit LPL activity in the presence of increasing concentrations of ANGPTL3/8 was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. Control (squares) and HSA-His–alone (triangles) conditions are also shown. Results are shown as the mean ± SD (n = 3 from three independent experiments). B: The ability of 100 nM PreScission-cleaved HSA-ApoA5 (diamonds) and 100 nM PreScission-cleaved ApoA5-HSA (circles) to inhibit the LPL activity in the presence of increasing concentrations of ANGPTL3/8 was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. Control (squares) and HSA-His alone plus PreScission cleavage (triangles) are also shown. Results are shown as the mean ± SD (n = 3 from three independent experiments). ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.
Fig. 5 HSA-ApoA5 and ApoA5-HSA block ANGPTL3/8-mediated LPL inhibitory activity in a similar manner to PreScission-cleaved HSA-ApoA5 and PreScission-cleaved ApoA5-HSA. A: The ability of 100 nM HSA-ApoA5 (diamonds) and 100 nM ApoA5-HSA (circles) to inhibit LPL activity in the presence of increasing concentrations of ANGPTL3/8 was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. Control (squares) and HSA-His–alone (triangles) conditions are also shown. Results are shown as the mean ± SD (n = 3 from three independent experiments). B: The ability of 100 nM PreScission-cleaved HSA-ApoA5 (diamonds) and 100 nM PreScission-cleaved ApoA5-HSA (circles) to inhibit the LPL activity in the presence of increasing concentrations of ANGPTL3/8 was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. Control (squares) and HSA-His alone plus PreScission cleavage (triangles) are also shown. Results are shown as the mean ± SD (n = 3 from three independent experiments). ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.CC BY · PubMed Central
Fig. 6 Further characterization of ApoA5 suppression of ANGPTL3/8-mediated LPL inhibition. A: The ability of ANGPTL3/8 to inhibit LPL activity using VLDL as a substrate was assessed in the presence of 0 nM (squares), 25 nM (triangles), 100 nM (diamonds), and 300 nM (circles) of ApoA5 (HSA-ApoA5). The assay was performed with VLDL as a substrate, and NEFA levels were measured. Results are shown as the mean ± SD (n = 4 from two independent experiments). B: Biolayer interferometry was used to assess the binding of the immobilized anti-ANGPTL3/8 antibody to the ANGPTL3/8 complex after preincubation of ANGPTL3/8 with ApoA5. (C) Biolayer interferometry was used to assess the binding of the immobilized anti-ANGPTL3 antibody to the ANGPTL3/8 complex after preincubation of ANGPTL3/8 with ApoA5. D: Biolayer interferometry was used to assess the binding of the immobilized anti-ANGPTL8 antibody to the ANGPTL3/8 complex after preincubation of ANGPTL3/8 with ApoA5. ANGPTL8, angiopoietin-like protein 8.
Fig. 6 Further characterization of ApoA5 suppression of ANGPTL3/8-mediated LPL inhibition. A: The ability of ANGPTL3/8 to inhibit LPL activity using VLDL as a substrate was assessed in the presence of 0 nM (squares), 25 nM (triangles), 100 nM (diamonds), and 300 nM (circles) of ApoA5 (HSA-ApoA5). The assay was performed with VLDL as a substrate, and NEFA levels were measured. Results are shown as the mean ± SD (n = 4 from two independent experiments). B: Biolayer interferometry was used to assess the binding of the immobilized anti-ANGPTL3/8 antibody to the ANGPTL3/8 complex after preincubation of ANGPTL3/8 with ApoA5. (C) Biolayer interferometry was used to assess the binding of the immobilized anti-ANGPTL3 antibody to the ANGPTL3/8 complex after preincubation of ANGPTL3/8 with ApoA5. D: Biolayer interferometry was used to assess the binding of the immobilized anti-ANGPTL8 antibody to the ANGPTL3/8 complex after preincubation of ANGPTL3/8 with ApoA5. ANGPTL8, angiopoietin-like protein 8.CC BY · PubMed Central
Fig. 7 Analyses of ApoA5 effect on ANGPTL3/8-mediated LPL inhibition. A: The ability of 1.2 nM of ANGPTL3/8 to inhibit LPL activity in the presence of HSA-ApoA5 was assessed via kinetic analyses using LPL-stable expression cells with EnzChek fluorescent lipase substrate. ANGPTL3/8 was preincubated with 0 nM (red squares), 25 nM (green triangles), 100 nM (purple triangles), or 300 nM (orange diamonds) of HSA-ApoA5 before the addition of lipase substrate. The control condition (blue circles) indicates the absence of ANGPTL3/8 and ApoA5. Results are representative of three independent experiments. B: The effect of HSA-ApoA5 (circles) on the ability of 0.3 nM ANGPTL3/8 (the IC60 of ANGPTL3/8) to inhibit LPL was assessed using LPL-stable expression cells. ANGPTL3/8 was preincubated with increasing concentrations of HSA-ApoA5 before the addition of lipase substrate. The effect of HSA alone (triangles) was also evaluated. Results are shown as the mean ± SD (n = 4 from two independent experiments). ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.
Fig. 7 Analyses of ApoA5 effect on ANGPTL3/8-mediated LPL inhibition. A: The ability of 1.2 nM of ANGPTL3/8 to inhibit LPL activity in the presence of HSA-ApoA5 was assessed via kinetic analyses using LPL-stable expression cells with EnzChek fluorescent lipase substrate. ANGPTL3/8 was preincubated with 0 nM (red squares), 25 nM (green triangles), 100 nM (purple triangles), or 300 nM (orange diamonds) of HSA-ApoA5 before the addition of lipase substrate. The control condition (blue circles) indicates the absence of ANGPTL3/8 and ApoA5. Results are representative of three independent experiments. B: The effect of HSA-ApoA5 (circles) on the ability of 0.3 nM ANGPTL3/8 (the IC60 of ANGPTL3/8) to inhibit LPL was assessed using LPL-stable expression cells. ANGPTL3/8 was preincubated with increasing concentrations of HSA-ApoA5 before the addition of lipase substrate. The effect of HSA alone (triangles) was also evaluated. Results are shown as the mean ± SD (n = 4 from two independent experiments). ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.CC BY · PubMed Central
Fig. 8 Kinetic analyses of the effect of ApoA5 on LPL-inhibitory activities of ANGPTL4, ANGPTL3, and ANGPTL4/8. The ability of ANGPTL4, ANGPTL3, or ANGPTL4/8 (each at 1.2 nM) to inhibit LPL activity in the presence of different concentrations of ApoA5 (HSA-ApoA5) at 0 nM (red squares), 25 nM (green triangles), 100 nM (purple triangles), and 300 nM (orange diamonds) was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. The control condition (blue circles) indicates the absence of ApoA5 and each respective ANGPTL protein or complex. All results are representative of three independent experiments. (A) ANGPTL4 was preincubated with ApoA5 before the addition of lipase substrate. B: ANGPTL3 was preincubated with ApoA5 before the addition of lipase substrate. C: ANGPTL4/8 was preincubated with ApoA5 before the addition of lipase substrate. D: The effect of ApoA5 alone at 0 nM (blue circles), 25 nM (green triangles), 100 nM (purple triangles), and 300 nM (orange diamonds) on the LPL activity was assessed using LPL-stable expression cells. ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.
Fig. 8 Kinetic analyses of the effect of ApoA5 on LPL-inhibitory activities of ANGPTL4, ANGPTL3, and ANGPTL4/8. The ability of ANGPTL4, ANGPTL3, or ANGPTL4/8 (each at 1.2 nM) to inhibit LPL activity in the presence of different concentrations of ApoA5 (HSA-ApoA5) at 0 nM (red squares), 25 nM (green triangles), 100 nM (purple triangles), and 300 nM (orange diamonds) was assessed using LPL-stable expression cells with EnzChek fluorescent lipase substrate. The control condition (blue circles) indicates the absence of ApoA5 and each respective ANGPTL protein or complex. All results are representative of three independent experiments. (A) ANGPTL4 was preincubated with ApoA5 before the addition of lipase substrate. B: ANGPTL3 was preincubated with ApoA5 before the addition of lipase substrate. C: ANGPTL4/8 was preincubated with ApoA5 before the addition of lipase substrate. D: The effect of ApoA5 alone at 0 nM (blue circles), 25 nM (green triangles), 100 nM (purple triangles), and 300 nM (orange diamonds) on the LPL activity was assessed using LPL-stable expression cells. ANGPTL8, angiopoietin-like protein 8; HSA, human serum albumin.CC BY · PubMed Central
Fig. 9 Human ApoA5 shows markedly decreased potency in suppressing mouse ANGPTL3/8-mediated inhibition of mouse LPL activity. A: Kinetic analyses were performed to assess the effect of human ApoA5 on mouse ANGPTL3/8. The ability of 1.2 nM mouse ANGPTL3/8 to inhibit mouse LPL in the presence of different concentrations of human ApoA5 (HSA-ApoA5) at 0 nM (red squares), 25 nM (green triangles), 100 nM (purple triangles), and 300 nM (orange diamonds) was assessed using mouse LPL-stable expression cells with EnzChek fluorescent lipase substrate. The control condition (blue circles) indicates the absence of both human ApoA5 and mouse ANGPTL3/8. Results are representative of three independent experiments. B: The ability of 0.4 nM mouse ANGPTL3/8 to inhibit mouse LPL activity in the presence of the same concentrations of human ApoA5 used in Fig. 9A was assessed using mouse LPL-stable expression cells with EnzChek fluorescent lipase substrate. The control condition indicates the absence of both human ApoA5 and mouse ANGPTL3/8. Results are representative of 3 independent experiments. ANGPTL8, angiopoietin-like protein 8.
Fig. 9 Human ApoA5 shows markedly decreased potency in suppressing mouse ANGPTL3/8-mediated inhibition of mouse LPL activity. A: Kinetic analyses were performed to assess the effect of human ApoA5 on mouse ANGPTL3/8. The ability of 1.2 nM mouse ANGPTL3/8 to inhibit mouse LPL in the presence of different concentrations of human ApoA5 (HSA-ApoA5) at 0 nM (red squares), 25 nM (green triangles), 100 nM (purple triangles), and 300 nM (orange diamonds) was assessed using mouse LPL-stable expression cells with EnzChek fluorescent lipase substrate. The control condition (blue circles) indicates the absence of both human ApoA5 and mouse ANGPTL3/8. Results are representative of three independent experiments. B: The ability of 0.4 nM mouse ANGPTL3/8 to inhibit mouse LPL activity in the presence of the same concentrations of human ApoA5 used in Fig. 9A was assessed using mouse LPL-stable expression cells with EnzChek fluorescent lipase substrate. The control condition indicates the absence of both human ApoA5 and mouse ANGPTL3/8. Results are representative of 3 independent experiments. ANGPTL8, angiopoietin-like protein 8.CC BY · PubMed Central
Fig. 10 Effect of insulin or the LXR agonist T0901317 on hepatocyte secretion of ANGPTL3/8 and ApoA5. A: Human primary hepatocytes were preincubated in application media in the absence of insulin. After aspiration, cells were incubated with application media in the presence of 0–1 nM insulin. ANGPTL3/8 (filled triangles) and ApoA5 (open circles) secreted into the media were measured using immunoassays, with the results shown as the mean ± SEM (n = 8 from 2 independent experiments, ∗P < 0.01). B: Human primary hepatocytes were preincubated in application media in the absence of insulin. After aspiration, cells were incubated with application media in the presence of 0–10,000 nM T0901317. ANGPTL3/8 (filled triangles) and ApoA5 (open circles) secreted into the media were measured using immunoassays, with the results shown as the mean ± SEM (n = 8 from two independent experiments, ∗P < 0.01). ANGPTL8, angiopoietin-like protein 8.
Fig. 10 Effect of insulin or the LXR agonist T0901317 on hepatocyte secretion of ANGPTL3/8 and ApoA5. A: Human primary hepatocytes were preincubated in application media in the absence of insulin. After aspiration, cells were incubated with application media in the presence of 0–1 nM insulin. ANGPTL3/8 (filled triangles) and ApoA5 (open circles) secreted into the media were measured using immunoassays, with the results shown as the mean ± SEM (n = 8 from 2 independent experiments, ∗P < 0.01). B: Human primary hepatocytes were preincubated in application media in the absence of insulin. After aspiration, cells were incubated with application media in the presence of 0–10,000 nM T0901317. ANGPTL3/8 (filled triangles) and ApoA5 (open circles) secreted into the media were measured using immunoassays, with the results shown as the mean ± SEM (n = 8 from two independent experiments, ∗P < 0.01). ANGPTL8, angiopoietin-like protein 8.CC BY · PubMed Central
Fig. 11 Effect of the combination of insulin and the LXR agonist T0901317 on hepatocyte secretion of ANGPTL3/8 and ApoA5. A: Human primary hepatocytes were preincubated in application media in the absence of insulin. After aspiration, cells were incubated with application media in the presence of 0–1 nM insulin and 0–10,000 nM T0901317. ANGPTL3/8 levels in the media were measured using an immunoassay, with the results shown as the mean ± SEM (n = 8 from two independent experiments, ∗P < 0.001). B: ApoA5 levels from the exact same media samples collected in Fig. 11A were measured using an immunoassay, with the results shown as the mean ± SEM (n = 8 from two independent experiments, ∗P < 0.01). ANGPTL8, angiopoietin-like protein 8.
Fig. 11 Effect of the combination of insulin and the LXR agonist T0901317 on hepatocyte secretion of ANGPTL3/8 and ApoA5. A: Human primary hepatocytes were preincubated in application media in the absence of insulin. After aspiration, cells were incubated with application media in the presence of 0–1 nM insulin and 0–10,000 nM T0901317. ANGPTL3/8 levels in the media were measured using an immunoassay, with the results shown as the mean ± SEM (n = 8 from two independent experiments, ∗P < 0.001). B: ApoA5 levels from the exact same media samples collected in Fig. 11A were measured using an immunoassay, with the results shown as the mean ± SEM (n = 8 from two independent experiments, ∗P < 0.01). ANGPTL8, angiopoietin-like protein 8.CC BY · PubMed Central

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Cited by

Sorted by citations

Metadata

Authors
Chen, Y. Q., Pottanat, T. G., Zhen, E. Y., Siegel, R. W., Ehsani, M., Qian, Y.-W., & Konrad, R. J.
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2021
Volume
62
Pages
100068
ISSN
0022-2275
DOI
10.1016/j.jlr.2021.100068
PMC
PMC8079461
Cited by
82
References
1
Language
en
Licence
Funders
Eli Lilly and Company

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