Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism

Nishimura, Kenji; Murakami, Taichi; Sakurai, ﻿Toshihiro; Miyoshi, Masashi; Kurahashi, Kiyoe; Kishi, Seiji; Tamaki, Masanori; Tominaga, Tatsuya; Yoshida, Sumiko; Nagai, Kojiro; Abe, Hideharu; Hui, Shu‐Ping; Kotani, Kazuhiko; Doi, Toshio

doi:10.1038/s41598-019-51367-7

Cited by 12 publications

(16 citation statements)

References 41 publications

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“…It should be noted, however, that we were not able to discriminate the multiple isoforms of apoJ in the present study. ApoL1 also circulates primarily as a component of HDL [ 38 ]. Its plasma levels are correlated with plasma TG [ 39 ], a finding we also observed in our study population.…”

Section: Discussionmentioning

confidence: 99%

“…Its plasma levels are correlated with plasma TG [ 39 ], a finding we also observed in our study population. The plasma levels of apoL1 have been reported to be increased in patients with metabolic syndrome, and an in vitro study has demonstrated that the insulin signaling pathway regulates both the synthesis and the secretion of apoL1 in hepatocytes [ 38 ]. In agreement with previous findings [ 38 ], we found a significant and positive correlation between apoL1 and HOMA-IR as well as an inverse correlation with plasma adiponectin, reinforcing its potential role in insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

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Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Croyal

Wargny

Chemello

et al. 2022

Cardiovasc Diabetol

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Background The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up. Methods In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models. Results During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (< 5.97 mg/dL) was significantly associated with a lower risk of conversion to T2D (log-rank test, p = 0.002) compared to the middle and upper thirds. Conclusions The plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Croyal

Wargny

Chemello

et al. 2022

Cardiovasc Diabetol

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“…8,13,22,23 Although we cannot exclude the possibility that ER APOL1 "drowns out" the signal in other compartments, we suspect that the far more abundant APOL2 and/or suboptimal staining procedures, epitope tags, transfection artifacts, or different cell types may have contributed to previously published results. At least some of the APOL1 within the ER cisternae is adjacent to (although not specifically enriched in) the MAM, a subdomain of the ER associated with lipid synthesis and ER stress signaling, 43 which is interesting because APOL1 has been reported to affect lipid metabolism, 47 reverse cholesterol efflux, 16 and ER stress. 21,28 Because acidic pH is required for membrane insertion of APOL1, [49][50][51] we expected APOL1 to be soluble in the neutral 52 ER lumen.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein L1-Specific Antibodies Detect Endogenous APOL1 inside the Endoplasmic Reticulum and on the Plasma Membrane of Podocytes

Scales¹,

Gupta²,

Mazière

et al. 2020

JASN

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BackgroundAPOL1 is found in human kidney podocytes and endothelia. Variants G1 and G2 of the APOL1 gene account for the high frequency of nondiabetic CKD among African Americans. Proposed mechanisms of kidney podocyte cytotoxicity resulting from APOL1 variant overexpression implicate different subcellular compartments. It is unclear where endogenous podocyte APOL1 resides, because previous immunolocalization studies utilized overexpressed protein or commercially available antibodies that crossreact with APOL2. This study describes and distinguishes the locations of both APOLs.MethodsImmunohistochemistry, confocal and immunoelectron microscopy, and podocyte fractionation localized endogenous and transfected APOL1 using a large panel of novel APOL1-specific mouse and rabbit monoclonal antibodies.ResultsBoth endogenous podocyte and transfected APOL1 isoforms vA and vB1 (and a little of isoform vC) localize to the luminal face of the endoplasmic reticulum (ER) and to the cell surface, but not to mitochondria, endosomes, or lipid droplets. In contrast, APOL2, isoform vB3, and most vC of APOL1 localize to the cytoplasmic face of the ER and are consequently absent from the cell surface. APOL1 knockout podocytes do not stain for APOL1, attesting to the APOL1-specificity of the antibodies. Stable re-transfection of knockout podocytes with inducible APOL1-G0, -G1, and -G2 showed no differences in localization among variants.ConclusionsAPOL1 is found in the ER and plasma membrane, consistent with either the ER stress or surface cation channel models of APOL1-mediated cytotoxicity. The surface localization of APOL1 variants potentially opens new therapeutic targeting avenues.

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“…The blood cholesterol concentration is mainly dependent on the production, absorption, and catabolism of cholesterol in the liver and intestinal tract [ 20 ]. The measurement of TC content is important as an index of abnormal lipid metabolism in the body [ 21 ]. In addition, as the degree of obesity increased, the TC content increased, and serum TC content was significant for obesity.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

et al. 2021

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Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg−1∙d−1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg−1∙d−1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

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Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism

Cited by 12 publications

References 41 publications

Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Apolipoprotein L1-Specific Antibodies Detect Endogenous APOL1 inside the Endoplasmic Reticulum and on the Plasma Membrane of Podocytes

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

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