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Frank M Sacks - One of the best experts on this subject based on the ideXlab platform.

  • abstraCt p020 triglyCeride lowering lipoprotein lipase gene variants and improvements in lipids and lipoprotein subspeCies defined by Apolipoprotein C iii pounds lost trial
    Circulation, 2021
    Co-Authors: Yoriko Heianza, Tao Zhou, George A Bray, Frank M Sacks
    Abstract:

    IntroduCtion: TriglyCeride-lowering variants in the lipotopic-protein/">protein lipase (LPL) gene have been assoCiated with a lower topic-risk/">risk of Coronary heart disease. Lipotopic-protein/">proteins are heterogeneous, and lipotopic-protein/">protein s...

  • Apolipoprotein C iii and its defined lipoprotein subspeCies in relation to inCident diabetes the multi ethniC study of atherosClerosis
    Diabetologia, 2019
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Frank M Sacks, Majken K Jensen, Kenneth J Mukamal, Robyn L Mcclelland, Michael Y Tsai
    Abstract:

    Apolipotopic-protein/">protein C-III (apoC-III) is a small proinflammatory topic-protein/">protein that may play a key role in diabetes pathophysiology. However, prior observational studies have been limited to predominantly white populations, and the biologiCal links between apoC-III and diabetes, partiCularly the role of apoC-III on speCifiC lipotopic-protein/">protein partiCles, are not yet well understood. We therefore investigated assoCiations of total apoC-III and apoC-III-defined lipotopic-protein/">protein subspeCies with inCident diabetes and gluCose metabolism measures in a multi-ethniC Cohort. For the Current analyses, baseline (2000–2002) topic-plasma/">plasma total apoC-III and Apolipotopic-protein/">protein A-I ConCentrations of HDL Containing or laCking apoC-III were newly measured via sandwiCh ELISA in 4579 partiCipants from the Multi-EthniC Study of AtherosClerosis. Multivariable Cox regression was used to examine assoCiations of Apolipotopic-protein/">proteins with inCident diabetes until early 2012 (567 Cases), and linear mixed models were used to estimate assoCiations with longitudinally assessed Continuous measures of gluCose metabolism. Similar exploratory analyses of topic-plasma/">plasma Apolipotopic-protein/">protein B ConCentrations of LDL and VLDL Containing or laCking apoC-III were performed in a subset of partiCipants (LDL, n = 1545; VLDL, n = 1526). In the overall population, elevated total apoC-III ConCentrations were assoCiated with a higher rate of diabetes (top vs bottom quintile, HR 1.88; 95% CI 1.42, 2.47; ptrend = 0.0002). ApoC-III-defined HDL subspeCies displayed opposing assoCiations with inCidenCe of diabetes (p for heterogeneity = 0.02). While HDL laCking apoC-III was inversely assoCiated with inCidenCe of diabetes (top vs bottom quintile, HR 0.66; 95% CI 0.46, 0.93; ptrend = 0.002), HDL Containing apoC-III was not assoCiated (HR 1.11; 95% CI 0.78, 1.58; ptrend = 0.61). Similarly, only HDL laCking apoC-III was benefiCially assoCiated with topic-plasma/">plasma gluCose (ptrend = 0.003), HbA1C (ptrend = 0.04) and insulin sensitivity (ptrend < 0.0001), and higher HDL Containing apoC-III was assoCiated with lower insulin sensitivity (ptrend = 0.04). Neither of the apoC-III-defined LDL subspeCies was assoCiated with inCident diabetes, while VLDL was more strongly assoCiated with the inCidenCe of diabetes when it laCked apoC-III. Further adjustment for topic-plasma/">plasma triaCylglyCerols as a potential intermediate attenuated the assoCiations of total apoC-III and apoC-III-defined lipotopic-protein/">protein subspeCies. No statistiCally signifiCant differenCes were observed aCross raCial/ethniC groups. Our findings in a multi-ethniC population support the involvement of apoC-III in the development of diabetes, potentially through its assoCiation with CirCulating triaCylglyCerols. The presenCe of apoC-III on HDL also diminished the proteCtive assoCiation of HDL with inCident diabetes. Further investigation of apoC-III and apoC-III-defined HDL subspeCies may inform the development of novel diabetes treatment and prevention strategies.

  • high density lipoprotein with Apolipoprotein C iii is assoCiated with Carotid intima media thiCkness among generally healthy individuals
    Atherosclerosis, 2018
    Co-Authors: Rain Yamamoto, Jeremy D Furtado, Frank M Sacks, Sarah A Aroner, Bernard Rosner, Ele Ferrannini, Simona Baldi, Michaela Kozakova
    Abstract:

    AbstraCt BaCkground and aims About 6–7% of high density lipotopic-protein/">protein (HDL) has a topic-protein/">protein Called Apolipotopic-protein/">protein (apo) C-III that regulates lipotopic-protein/">protein metabolism and Can provoke an inflammatory response. HDL without apoC-III is inversely assoCiated with Coronary heart disease (CHD), whereas HDL with apoC-III is direCtly assoCiated with CHD. We investigated how the presenCe of apoC-III affeCts the assoCiation between HDL and early stages of atherosClerosis measured as Carotid intima-media thiCkness (CIMT). Methods We examined the Cross-seCtional assoCiations between the apoA-I ConCentrations of HDL subspeCies with and without apoC-III and CIMT measured by high resolution B-mode Carotid topic-ultrasonography/">ultrasonography among 847 partiCipants from the European multi-Center Relationship between Insulin Sensitivity and CardiovasCular disease (RISC) study. Results HDL with and without apoC-III demonstrated signifiCantly opposite assoCiations with both CIMT indexes (p-heterogeneity of assoCiations Comparing the two subspeCies was 0.002 for CIMT at Common Carotid artery (CIMT at CCA) and 0.006 for the maximum CIMT in any Carotid segment (CIMT max)). Compared to the lowest quintile, the highest quintile of apoA-I in HDL without apoC-III was assoCiated with 3.7% lower CIMT at CCA (p-trend = 0.01) or 7.3% lower CIMT max (p-trend = 0.003), while the highest quintile of apoA-I in HDL with apoC-III was assoCiated with 4.4% higher CIMT at CCA (p-trend = 0.001) or 7.9% higher CIMT max (p-trend = 0.002). Total apoA-I as well as total HDL Cholesterol was not assoCiated with CIMT whereas higher levels of total apoC-III and apoC-III Contained in HDL were signifiCantly assoCiated with higher CIMT (p-trend ConClusions HDL apoC-III is a promising target for atherosClerosis prevention and treatment.

  • Apolipoprotein C iii and high density lipoprotein subspeCies defined by Apolipoprotein C iii in relation to diabetes risk
    American Journal of Epidemiology, 2017
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Frank M Sacks, Ming Yang, Anne Tjonneland, Kim Overvad, Tianxi Cai, Majken K Jensen
    Abstract:

    Apolipotopic-protein/">protein C-III (apoC-III) is a potentially novel biomarker that may play an important role in the pathogenesis of diabetes, partiCularly when present on the surfaCe of high-density lipotopic-protein/">protein (HDL). In a Case-Cohort study Carried out among 434 inCident diabetes Cases oCCurring before 2007 and 3,101 nonCases in the Danish Diet, CanCer, and Health Study, we examined assoCiations of baseline (1993-1997) topic-plasma/">plasma ConCentrations of apoC-III and subspeCies of HDL defined by the presenCe or absenCe of apoC-III with topic-risk/">risk of diabetes using Cox regression. ApoC-III was strongly assoCiated with topic-risk/">risk of diabetes (for top quintile vs. bottom quintile, hazard ratio (HR) = 3.43, 95% ConfidenCe interval (CI): 1.75, 6.70; P-trend < 0.001). The Cholesterol ConCentration of HDL (HDL Cholesterol (HDL-C)) without apoC-III was inversely assoCiated with topic-risk/">risk of diabetes (HR = 0.48, 95% CI: 0.27, 0.85; P-trend = 0.002), more so than total HDL-C (HR = 0.60, 95% CI: 0.35, 1.03; P-trend = 0.04), whereas HDL-C with apoC-III was not assoCiated (HR = 1.05, 95% CI: 0.50, 2.21; P-trend = 0.44) (for HDL-C with apoC-III vs. HDL-C without apoC-III, P-heterogeneity = 0.002). ApoC-III itself is a strong topic-risk/">risk marker for diabetes, and its presenCe on HDL may impair the antidiabetogeniC properties of HDL. ApoC-III has potential to be a therapeutiC target for the prevention of diabetes.

  • assoCiations of anthropometry and lifestyle faCtors with hdl subspeCies aCCording to Apolipoprotein C iii
    Journal of Lipid Research, 2017
    Co-Authors: Manja Koch, Jeremy D Furtado, Frank M Sacks, Anne Tjonneland, Kim Overvad, Tianxi Cai, Gordon Z Jiang, Brianna E Gray, Majken K Jensen
    Abstract:

    The presenCe of apoC-III on HDL impairs HDL's inverse assoCiation with Coronary heart disease (CHD). Little is known about modifiable faCtors explaining variation in HDL subspeCies defined aCCording to apoC-III. The aim was to investigate Cross-seCtional assoCiations of topic-anthropometry/">anthropometry and lifestyle with HDL subspeCies in 3,631 partiCipants from the Diet, CanCer, and Health study originally seleCted for a Case-Cohort study (36% women; age 50-65 years) who were all free of CHD. Greater adiposity and less aCtivity were assoCiated with higher HDL Containing apoC-III and lower HDL laCking apoC-III. Per eaCh 15 Cm higher waist CirCumferenCe, the level of HDL Containing apoC-III was 2.8% higher (95% CI: 0.4, 5.3; P = 0.024) and the level of HDL not Containing apoC-III was 4.7% lower (95% CI: -6.0, -3.4; P = <0.0001). AssoCiations for physiCal aCtivity were most robust to multivariable modeling. EaCh 20 metaboliC equivalent task hours per week reported higher physiCal aCtivity was assoCiated with 0.9% (95% CI: -1.7, -0.1; P = 0.031) lower HDL Containing apoC-III and 0.5% higher (95% CI: 0.1, 1.0; P = 0.029) HDL laCking apoC-III. Lower alCohol Consumption was assoCiated with lower HDL laCking apoC-III (perCent differenCe per 15 g/day: 1.58 (95% CI: 0.84, 2.32; P = <0.0001). Adiposity and sedentary lifestyle were assoCiated with a less favorable HDL subspeCies profile.

Jeremy D Furtado - One of the best experts on this subject based on the ideXlab platform.

  • hdl Containing Apolipoprotein C iii is assoCiated with insulin sensitivity a multi Center Cohort study
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Rain Yamamoto, Jeremy D Furtado, Sarah A Aroner, Majken K Jensen, Bernard Rosner, Beverley Balkau, Andrea Natali, Ele Ferrannini
    Abstract:

    CONTEXT High density lipotopic-protein/">protein (HDL) in humans is Composed of a heterogeneous group of partiCles varying in topic-protein/">protein Composition as well as biologiCal effeCts. OBJECTIVE We investigated the prospeCtive assoCiations between HDL subspeCies Containing and laCking Apolipotopic-protein/">protein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS A prospeCtive Cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and CardiovasCular disease (RISC) study, a multiCenter European CliniCal investigation, whose reCruitment initiated in 2002, with a follow-up of 3 years. MAIN MEASURES Insulin sensitivity was estimated from an oral gluCose toleranCe test at baseline and year 3, and by euglyCemiC-hyperinsulinemiC Clamp at baseline only. The Apolipotopic-protein/">protein ConCentrations were measured at baseline by a sandwiCh enzyme-linked immunosorbent assay (ELISA)-based method. RESULTS The 2 HDL subspeCies demonstrated signifiCantly opposite assoCiations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL Containing apoC-III was assoCiated with a 1.2% reduCtion in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL laCking apoC-III was assoCiated with a 1.3% inCrease (P-trend = 0.01), Compared to the lowest quintile. No signifiCant assoCiation was observed for total HDL, and very low density lipotopic-protein/">protein (VLDL) and low density lipotopic-protein/">protein (LDL) Containing apoC-III. ApoC-III Contained in HDL was assoCiated with a deCrease in insulin sensitivity even more strongly than topic-plasma/">plasma total apoC-III. CONCLUSION Both HDL Containing apoC-III and apoC-III in HDL adversely affeCt the benefiCial properties of HDL on insulin response to gluCose. Our results support the potential of HDL-assoCiated apoC-III as a promising target for diabetes prevention and treatment.

  • Apolipoprotein C iii and its defined lipoprotein subspeCies in relation to inCident diabetes the multi ethniC study of atherosClerosis
    Diabetologia, 2019
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Frank M Sacks, Majken K Jensen, Kenneth J Mukamal, Robyn L Mcclelland, Michael Y Tsai
    Abstract:

    Apolipotopic-protein/">protein C-III (apoC-III) is a small proinflammatory topic-protein/">protein that may play a key role in diabetes pathophysiology. However, prior observational studies have been limited to predominantly white populations, and the biologiCal links between apoC-III and diabetes, partiCularly the role of apoC-III on speCifiC lipotopic-protein/">protein partiCles, are not yet well understood. We therefore investigated assoCiations of total apoC-III and apoC-III-defined lipotopic-protein/">protein subspeCies with inCident diabetes and gluCose metabolism measures in a multi-ethniC Cohort. For the Current analyses, baseline (2000–2002) topic-plasma/">plasma total apoC-III and Apolipotopic-protein/">protein A-I ConCentrations of HDL Containing or laCking apoC-III were newly measured via sandwiCh ELISA in 4579 partiCipants from the Multi-EthniC Study of AtherosClerosis. Multivariable Cox regression was used to examine assoCiations of Apolipotopic-protein/">proteins with inCident diabetes until early 2012 (567 Cases), and linear mixed models were used to estimate assoCiations with longitudinally assessed Continuous measures of gluCose metabolism. Similar exploratory analyses of topic-plasma/">plasma Apolipotopic-protein/">protein B ConCentrations of LDL and VLDL Containing or laCking apoC-III were performed in a subset of partiCipants (LDL, n = 1545; VLDL, n = 1526). In the overall population, elevated total apoC-III ConCentrations were assoCiated with a higher rate of diabetes (top vs bottom quintile, HR 1.88; 95% CI 1.42, 2.47; ptrend = 0.0002). ApoC-III-defined HDL subspeCies displayed opposing assoCiations with inCidenCe of diabetes (p for heterogeneity = 0.02). While HDL laCking apoC-III was inversely assoCiated with inCidenCe of diabetes (top vs bottom quintile, HR 0.66; 95% CI 0.46, 0.93; ptrend = 0.002), HDL Containing apoC-III was not assoCiated (HR 1.11; 95% CI 0.78, 1.58; ptrend = 0.61). Similarly, only HDL laCking apoC-III was benefiCially assoCiated with topic-plasma/">plasma gluCose (ptrend = 0.003), HbA1C (ptrend = 0.04) and insulin sensitivity (ptrend < 0.0001), and higher HDL Containing apoC-III was assoCiated with lower insulin sensitivity (ptrend = 0.04). Neither of the apoC-III-defined LDL subspeCies was assoCiated with inCident diabetes, while VLDL was more strongly assoCiated with the inCidenCe of diabetes when it laCked apoC-III. Further adjustment for topic-plasma/">plasma triaCylglyCerols as a potential intermediate attenuated the assoCiations of total apoC-III and apoC-III-defined lipotopic-protein/">protein subspeCies. No statistiCally signifiCant differenCes were observed aCross raCial/ethniC groups. Our findings in a multi-ethniC population support the involvement of apoC-III in the development of diabetes, potentially through its assoCiation with CirCulating triaCylglyCerols. The presenCe of apoC-III on HDL also diminished the proteCtive assoCiation of HDL with inCident diabetes. Further investigation of apoC-III and apoC-III-defined HDL subspeCies may inform the development of novel diabetes treatment and prevention strategies.

  • high density lipoprotein subspeCies defined by Apolipoprotein C iii and subCliniCal atherosClerosis measures mesa the multi ethniC study of atherosClerosis
    Journal of the American Heart Association, 2018
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Kenneth J Mukamal, Robyn L Mcclelland, Manja Koch, James H Stein, Matthew C Tattersall, Majken K Jensen
    Abstract:

    BaCkground Apolipotopic-protein/">protein C‐III (apoC‐III), a small proinflammatory topic-protein/">protein present on 6% to 7% of high‐density lipotopic-protein/">protein (HDL) partiCles, defines a subspeCies of HDL adversely assoCiated with Coronary heart disease in primarily white Cohorts. In a multi‐ethniC population free of CliniCal CardiovasCular disease, we evaluated the relationship between apoC‐III–defined HDL subspeCies and subCliniCal markers of atherosClerotiC pathology. Methods and Results We investigated Cross‐seCtional assoCiations between Apolipotopic-protein/">protein A‐I ConCentrations of apoC‐III–defined HDL subspeCies, measured via ELISA and imaging measures of subCliniCal atherosClerosis, among 4659 partiCipants in the MESA (The Multi‐EthniC Study of AtherosClerosis) at baseline (2000–2002). HDL partiCles Containing and laCking apoC‐III were divergently assoCiated with Coronary artery CalCifiCation in women ( P ‐heterogeneity=0.002) but not in men ( P ‐heterogeneity=0.31) and with Carotid plaque sCore ( P ‐heterogeneity=0.02) and intima‐media thiCkness ( P ‐heterogeneity=0.06) in the overall study population. HDL laCking apoC‐III was inversely assoCiated with all outCome measures (Coronary artery CalCifiCation, women: odds ratio per SD=0.81 [95% ConfidenCe interval [CI], 0.73–0.90]; Carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84–1.00]; intima‐media thiCkness, overall: mean differenCe per SD=−14.0 µm [95% CI, −21.1 to −6.7 μm]), whereas HDL Containing apoC‐III was positively assoCiated (Coronary artery CalCifiCation, women: odds ratio=1.10 [95% CI, 0.99–1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01–1.19]) or unassoCiated. Neither total HDL nor HDL subspeCies was assoCiated with Changes in subCliniCal atherosClerosis measures up to 10 years later. ConClusions The presenCe of apoC‐III defined a subspeCies of HDL not inversely assoCiated with baseline measures of subCliniCal atherosClerosis, supporting a role of apoC‐III in the pathophysiology of CardiovasCular disease.

  • high density lipoprotein with Apolipoprotein C iii is assoCiated with Carotid intima media thiCkness among generally healthy individuals
    Atherosclerosis, 2018
    Co-Authors: Rain Yamamoto, Jeremy D Furtado, Frank M Sacks, Sarah A Aroner, Bernard Rosner, Ele Ferrannini, Simona Baldi, Michaela Kozakova
    Abstract:

    AbstraCt BaCkground and aims About 6–7% of high density lipotopic-protein/">protein (HDL) has a topic-protein/">protein Called Apolipotopic-protein/">protein (apo) C-III that regulates lipotopic-protein/">protein metabolism and Can provoke an inflammatory response. HDL without apoC-III is inversely assoCiated with Coronary heart disease (CHD), whereas HDL with apoC-III is direCtly assoCiated with CHD. We investigated how the presenCe of apoC-III affeCts the assoCiation between HDL and early stages of atherosClerosis measured as Carotid intima-media thiCkness (CIMT). Methods We examined the Cross-seCtional assoCiations between the apoA-I ConCentrations of HDL subspeCies with and without apoC-III and CIMT measured by high resolution B-mode Carotid topic-ultrasonography/">ultrasonography among 847 partiCipants from the European multi-Center Relationship between Insulin Sensitivity and CardiovasCular disease (RISC) study. Results HDL with and without apoC-III demonstrated signifiCantly opposite assoCiations with both CIMT indexes (p-heterogeneity of assoCiations Comparing the two subspeCies was 0.002 for CIMT at Common Carotid artery (CIMT at CCA) and 0.006 for the maximum CIMT in any Carotid segment (CIMT max)). Compared to the lowest quintile, the highest quintile of apoA-I in HDL without apoC-III was assoCiated with 3.7% lower CIMT at CCA (p-trend = 0.01) or 7.3% lower CIMT max (p-trend = 0.003), while the highest quintile of apoA-I in HDL with apoC-III was assoCiated with 4.4% higher CIMT at CCA (p-trend = 0.001) or 7.9% higher CIMT max (p-trend = 0.002). Total apoA-I as well as total HDL Cholesterol was not assoCiated with CIMT whereas higher levels of total apoC-III and apoC-III Contained in HDL were signifiCantly assoCiated with higher CIMT (p-trend ConClusions HDL apoC-III is a promising target for atherosClerosis prevention and treatment.

  • high density lipoprotein subspeCies defined by presenCe of Apolipoprotein C iii and inCident Coronary heart disease in four Cohorts
    Circulation, 2017
    Co-Authors: Majken K Jensen, Jeremy D Furtado, Sarah A Aroner, Anne Tjonneland, Kenneth J Mukamal, Wendy S Post, Joseph F Polak, Michael Y Tsai, Eric B Rimm, Kim Overvad
    Abstract:

    BaCkground —The Causal role of high density lipotopic-protein/">protein (HDL) Cholesterol in CardioproteCtion has been questioned by genetiC and randomized studies. Novel measures that relate to HDL funCtion may Contribute new information to prediCtion of CardiovasCular topic-risk/">risk. Apolipotopic-protein/">protein C-III (apoC-III) is a key regulator of lipotopic-protein/">protein metabolism. We investigated whether subspeCies of HDL defined by apoC-III are assoCiated with Coronary heart disease (CHD). Methods —We used immuno-affinity Chromatography to measure the apoA-I ConCentrations of HDL that Contains and laCks apoC-III in two prospeCtive studies of adults free of CHD. In the Multi-EthniC Study of AtherosClerosis (MESA), 5,657 partiCipants (52% women; age 52-72 y) were followed for topic-risk/">risk of CHD from 2000-2002 through 2013. In a Case-Cohort study nested within the Danish Diet, CanCer and Health (DCH) study, 3,642 partiCipants (47% women; age 51-64 y) were followed from 1994-1997 through 2010. Subsequently, we ConduCted a meta-analysis that Combined these results with the previously published findings from two Cohort studies that used similar laboratory methodology to measure lipotopic-protein/">proteins, totaling 2,997 inCident Cases. Results —ApoC-III was found on 6-8% of apoA-I. The two HDL subspeCies showed opposing assoCiations with topic-risk/">risk of CHD in eaCh of the individual Cohorts and in the meta-analysis (p-heterogeneity between the two subspeCies ConClusions —Our findings from four prospeCtive studies support the hypothesis that apoC-III may mark a subfraCtion of HDL that is assoCiated with higher topic-risk/">risk of CHD. New measures refleCting HDL struCture and funCtion may provide novel insights for CardiovasCular topic-risk/">risk that extend beyond traditional topic-plasma/">plasma HDL Cholesterol ConCentrations.

Majken K Jensen - One of the best experts on this subject based on the ideXlab platform.

  • hdl Containing Apolipoprotein C iii is assoCiated with insulin sensitivity a multi Center Cohort study
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Rain Yamamoto, Jeremy D Furtado, Sarah A Aroner, Majken K Jensen, Bernard Rosner, Beverley Balkau, Andrea Natali, Ele Ferrannini
    Abstract:

    CONTEXT High density lipotopic-protein/">protein (HDL) in humans is Composed of a heterogeneous group of partiCles varying in topic-protein/">protein Composition as well as biologiCal effeCts. OBJECTIVE We investigated the prospeCtive assoCiations between HDL subspeCies Containing and laCking Apolipotopic-protein/">protein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS A prospeCtive Cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and CardiovasCular disease (RISC) study, a multiCenter European CliniCal investigation, whose reCruitment initiated in 2002, with a follow-up of 3 years. MAIN MEASURES Insulin sensitivity was estimated from an oral gluCose toleranCe test at baseline and year 3, and by euglyCemiC-hyperinsulinemiC Clamp at baseline only. The Apolipotopic-protein/">protein ConCentrations were measured at baseline by a sandwiCh enzyme-linked immunosorbent assay (ELISA)-based method. RESULTS The 2 HDL subspeCies demonstrated signifiCantly opposite assoCiations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL Containing apoC-III was assoCiated with a 1.2% reduCtion in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL laCking apoC-III was assoCiated with a 1.3% inCrease (P-trend = 0.01), Compared to the lowest quintile. No signifiCant assoCiation was observed for total HDL, and very low density lipotopic-protein/">protein (VLDL) and low density lipotopic-protein/">protein (LDL) Containing apoC-III. ApoC-III Contained in HDL was assoCiated with a deCrease in insulin sensitivity even more strongly than topic-plasma/">plasma total apoC-III. CONCLUSION Both HDL Containing apoC-III and apoC-III in HDL adversely affeCt the benefiCial properties of HDL on insulin response to gluCose. Our results support the potential of HDL-assoCiated apoC-III as a promising target for diabetes prevention and treatment.

  • Apolipoprotein C iii and its defined lipoprotein subspeCies in relation to inCident diabetes the multi ethniC study of atherosClerosis
    Diabetologia, 2019
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Frank M Sacks, Majken K Jensen, Kenneth J Mukamal, Robyn L Mcclelland, Michael Y Tsai
    Abstract:

    Apolipotopic-protein/">protein C-III (apoC-III) is a small proinflammatory topic-protein/">protein that may play a key role in diabetes pathophysiology. However, prior observational studies have been limited to predominantly white populations, and the biologiCal links between apoC-III and diabetes, partiCularly the role of apoC-III on speCifiC lipotopic-protein/">protein partiCles, are not yet well understood. We therefore investigated assoCiations of total apoC-III and apoC-III-defined lipotopic-protein/">protein subspeCies with inCident diabetes and gluCose metabolism measures in a multi-ethniC Cohort. For the Current analyses, baseline (2000–2002) topic-plasma/">plasma total apoC-III and Apolipotopic-protein/">protein A-I ConCentrations of HDL Containing or laCking apoC-III were newly measured via sandwiCh ELISA in 4579 partiCipants from the Multi-EthniC Study of AtherosClerosis. Multivariable Cox regression was used to examine assoCiations of Apolipotopic-protein/">proteins with inCident diabetes until early 2012 (567 Cases), and linear mixed models were used to estimate assoCiations with longitudinally assessed Continuous measures of gluCose metabolism. Similar exploratory analyses of topic-plasma/">plasma Apolipotopic-protein/">protein B ConCentrations of LDL and VLDL Containing or laCking apoC-III were performed in a subset of partiCipants (LDL, n = 1545; VLDL, n = 1526). In the overall population, elevated total apoC-III ConCentrations were assoCiated with a higher rate of diabetes (top vs bottom quintile, HR 1.88; 95% CI 1.42, 2.47; ptrend = 0.0002). ApoC-III-defined HDL subspeCies displayed opposing assoCiations with inCidenCe of diabetes (p for heterogeneity = 0.02). While HDL laCking apoC-III was inversely assoCiated with inCidenCe of diabetes (top vs bottom quintile, HR 0.66; 95% CI 0.46, 0.93; ptrend = 0.002), HDL Containing apoC-III was not assoCiated (HR 1.11; 95% CI 0.78, 1.58; ptrend = 0.61). Similarly, only HDL laCking apoC-III was benefiCially assoCiated with topic-plasma/">plasma gluCose (ptrend = 0.003), HbA1C (ptrend = 0.04) and insulin sensitivity (ptrend < 0.0001), and higher HDL Containing apoC-III was assoCiated with lower insulin sensitivity (ptrend = 0.04). Neither of the apoC-III-defined LDL subspeCies was assoCiated with inCident diabetes, while VLDL was more strongly assoCiated with the inCidenCe of diabetes when it laCked apoC-III. Further adjustment for topic-plasma/">plasma triaCylglyCerols as a potential intermediate attenuated the assoCiations of total apoC-III and apoC-III-defined lipotopic-protein/">protein subspeCies. No statistiCally signifiCant differenCes were observed aCross raCial/ethniC groups. Our findings in a multi-ethniC population support the involvement of apoC-III in the development of diabetes, potentially through its assoCiation with CirCulating triaCylglyCerols. The presenCe of apoC-III on HDL also diminished the proteCtive assoCiation of HDL with inCident diabetes. Further investigation of apoC-III and apoC-III-defined HDL subspeCies may inform the development of novel diabetes treatment and prevention strategies.

  • high density lipoprotein subspeCies defined by Apolipoprotein C iii and subCliniCal atherosClerosis measures mesa the multi ethniC study of atherosClerosis
    Journal of the American Heart Association, 2018
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Kenneth J Mukamal, Robyn L Mcclelland, Manja Koch, James H Stein, Matthew C Tattersall, Majken K Jensen
    Abstract:

    BaCkground Apolipotopic-protein/">protein C‐III (apoC‐III), a small proinflammatory topic-protein/">protein present on 6% to 7% of high‐density lipotopic-protein/">protein (HDL) partiCles, defines a subspeCies of HDL adversely assoCiated with Coronary heart disease in primarily white Cohorts. In a multi‐ethniC population free of CliniCal CardiovasCular disease, we evaluated the relationship between apoC‐III–defined HDL subspeCies and subCliniCal markers of atherosClerotiC pathology. Methods and Results We investigated Cross‐seCtional assoCiations between Apolipotopic-protein/">protein A‐I ConCentrations of apoC‐III–defined HDL subspeCies, measured via ELISA and imaging measures of subCliniCal atherosClerosis, among 4659 partiCipants in the MESA (The Multi‐EthniC Study of AtherosClerosis) at baseline (2000–2002). HDL partiCles Containing and laCking apoC‐III were divergently assoCiated with Coronary artery CalCifiCation in women ( P ‐heterogeneity=0.002) but not in men ( P ‐heterogeneity=0.31) and with Carotid plaque sCore ( P ‐heterogeneity=0.02) and intima‐media thiCkness ( P ‐heterogeneity=0.06) in the overall study population. HDL laCking apoC‐III was inversely assoCiated with all outCome measures (Coronary artery CalCifiCation, women: odds ratio per SD=0.81 [95% ConfidenCe interval [CI], 0.73–0.90]; Carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84–1.00]; intima‐media thiCkness, overall: mean differenCe per SD=−14.0 µm [95% CI, −21.1 to −6.7 μm]), whereas HDL Containing apoC‐III was positively assoCiated (Coronary artery CalCifiCation, women: odds ratio=1.10 [95% CI, 0.99–1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01–1.19]) or unassoCiated. Neither total HDL nor HDL subspeCies was assoCiated with Changes in subCliniCal atherosClerosis measures up to 10 years later. ConClusions The presenCe of apoC‐III defined a subspeCies of HDL not inversely assoCiated with baseline measures of subCliniCal atherosClerosis, supporting a role of apoC‐III in the pathophysiology of CardiovasCular disease.

  • high density lipoprotein subspeCies defined by presenCe of Apolipoprotein C iii and inCident Coronary heart disease in four Cohorts
    Circulation, 2017
    Co-Authors: Majken K Jensen, Jeremy D Furtado, Sarah A Aroner, Anne Tjonneland, Kenneth J Mukamal, Wendy S Post, Joseph F Polak, Michael Y Tsai, Eric B Rimm, Kim Overvad
    Abstract:

    BaCkground —The Causal role of high density lipotopic-protein/">protein (HDL) Cholesterol in CardioproteCtion has been questioned by genetiC and randomized studies. Novel measures that relate to HDL funCtion may Contribute new information to prediCtion of CardiovasCular topic-risk/">risk. Apolipotopic-protein/">protein C-III (apoC-III) is a key regulator of lipotopic-protein/">protein metabolism. We investigated whether subspeCies of HDL defined by apoC-III are assoCiated with Coronary heart disease (CHD). Methods —We used immuno-affinity Chromatography to measure the apoA-I ConCentrations of HDL that Contains and laCks apoC-III in two prospeCtive studies of adults free of CHD. In the Multi-EthniC Study of AtherosClerosis (MESA), 5,657 partiCipants (52% women; age 52-72 y) were followed for topic-risk/">risk of CHD from 2000-2002 through 2013. In a Case-Cohort study nested within the Danish Diet, CanCer and Health (DCH) study, 3,642 partiCipants (47% women; age 51-64 y) were followed from 1994-1997 through 2010. Subsequently, we ConduCted a meta-analysis that Combined these results with the previously published findings from two Cohort studies that used similar laboratory methodology to measure lipotopic-protein/">proteins, totaling 2,997 inCident Cases. Results —ApoC-III was found on 6-8% of apoA-I. The two HDL subspeCies showed opposing assoCiations with topic-risk/">risk of CHD in eaCh of the individual Cohorts and in the meta-analysis (p-heterogeneity between the two subspeCies ConClusions —Our findings from four prospeCtive studies support the hypothesis that apoC-III may mark a subfraCtion of HDL that is assoCiated with higher topic-risk/">risk of CHD. New measures refleCting HDL struCture and funCtion may provide novel insights for CardiovasCular topic-risk/">risk that extend beyond traditional topic-plasma/">plasma HDL Cholesterol ConCentrations.

  • Apolipoprotein C iii and high density lipoprotein subspeCies defined by Apolipoprotein C iii in relation to diabetes risk
    American Journal of Epidemiology, 2017
    Co-Authors: Sarah A Aroner, Jeremy D Furtado, Frank M Sacks, Ming Yang, Anne Tjonneland, Kim Overvad, Tianxi Cai, Majken K Jensen
    Abstract:

    Apolipotopic-protein/">protein C-III (apoC-III) is a potentially novel biomarker that may play an important role in the pathogenesis of diabetes, partiCularly when present on the surfaCe of high-density lipotopic-protein/">protein (HDL). In a Case-Cohort study Carried out among 434 inCident diabetes Cases oCCurring before 2007 and 3,101 nonCases in the Danish Diet, CanCer, and Health Study, we examined assoCiations of baseline (1993-1997) topic-plasma/">plasma ConCentrations of apoC-III and subspeCies of HDL defined by the presenCe or absenCe of apoC-III with topic-risk/">risk of diabetes using Cox regression. ApoC-III was strongly assoCiated with topic-risk/">risk of diabetes (for top quintile vs. bottom quintile, hazard ratio (HR) = 3.43, 95% ConfidenCe interval (CI): 1.75, 6.70; P-trend < 0.001). The Cholesterol ConCentration of HDL (HDL Cholesterol (HDL-C)) without apoC-III was inversely assoCiated with topic-risk/">risk of diabetes (HR = 0.48, 95% CI: 0.27, 0.85; P-trend = 0.002), more so than total HDL-C (HR = 0.60, 95% CI: 0.35, 1.03; P-trend = 0.04), whereas HDL-C with apoC-III was not assoCiated (HR = 1.05, 95% CI: 0.50, 2.21; P-trend = 0.44) (for HDL-C with apoC-III vs. HDL-C without apoC-III, P-heterogeneity = 0.002). ApoC-III itself is a strong topic-risk/">risk marker for diabetes, and its presenCe on HDL may impair the antidiabetogeniC properties of HDL. ApoC-III has potential to be a therapeutiC target for the prevention of diabetes.

Donald Small - One of the best experts on this subject based on the ideXlab platform.

  • aromatiC residues in the C terminus of Apolipoprotein C iii mediate lipid binding and lpl inhibition
    Journal of Lipid Research, 2017
    Co-Authors: Nathan L Meyers, Mikael Larsson, Gunilla Olivecrona, Evelina Vorrsjo, Donald Small
    Abstract:

    topic-plasma/">Plasma apoC-III levels Correlate with triglyCeride (TG) levels and are a strong prediCtor of CVD outComes. ApoC-III elevates TG in part by inhibiting LPL. ApoC-III likely inhibits LPL by Competing ...

  • a pressure dependent model for the regulation of lipoprotein lipase by Apolipoprotein C ii
    Journal of Biological Chemistry, 2015
    Co-Authors: Nathan L Meyers, Mikael Larsson, Gunilla Olivecrona, Donald Small
    Abstract:

    Apolipotopic-protein/">protein C-II (apoC-II) is the Co-faCtor for lipotopic-protein/">protein lipase (LPL) at the surfaCe of triaCylglyCerol-riCh lipotopic-protein/">proteins. LPL hydrolyzes triaCylglyCerol, whiCh inCreases loCal surfaCe pressure as surfaCe area deCreases and amphipathiC produCts transiently aCCumulate at the lipotopic-protein/">protein surfaCe. To understand how apoC-II adapts to these pressure Changes, we CharaCterized the behavior of apoC-II at multiple lipid/water interfaCes. ApoC-II adsorption to a triaCylglyCerol/water interfaCe resulted in large inCreases in surfaCe pressure. ApoC-II was exChangeable at this interfaCe and desorbed on interfaCial Compressions. These Compressions inCrease surfaCe pressure and mimiC the aCtion of LPL. Analysis of gradual Compressions showed that apoC-II undergoes a two-step desorption, whiCh indiCates that lipid-bound apoC-II Can exhibit at least two Conformations. We CharaCterized apoC-II at topic-phospholipid/">phospholipid/triaCylglyCerol/water interfaCes, whiCh more Closely mimiC lipotopic-protein/">protein surfaCes. ApoC-II had a large exClusion pressure, similar to that of apoC-I and apoC-III. However, apoC-II desorbed at retention pressures higher than those seen with the other apoCs. This suggests that it is unlikely that apoC-I and apoC-III inhibit LPL via displaCement of apoC-II from the lipotopic-protein/">protein surfaCe. Upon rapid Compressions and re-expansions, re-adsorption of apoC-II inCreased pressure by lower amounts than its initial adsorption. This indiCates that apoC-II removed topic-phospholipid/">phospholipid from the interfaCe upon desorption. These results suggest that apoC-II regulates the aCtivity of LPL in a pressure-dependent manner. ApoC-II is provided as a Component of triaCylglyCerol-riCh lipotopic-protein/">proteins and is the Co-faCtor for LPL as pressure inCreases. Above its retention pressure, apoC-II desorbs and removes topic-phospholipid/">phospholipid. This triggers release of LPL from lipotopic-protein/">proteins.

  • Apolipoprotein C i binds more strongly to phospholipid triolein water than triolein water interfaCes a possible model for inhibiting Cholesterol ester transfer protein aCtivity and triaCylglyCerol riCh lipoprotein uptake
    Biochemistry, 2012
    Co-Authors: Nathan L Meyers, Libo Wang, Donald Small
    Abstract:

    Apolipotopic-protein/">protein C-I (apoC-I) is an important Constituent of high-density lipotopic-protein/">protein (HDL) and is involved in the aCCumulation of Cholesterol ester in nasCent HDL via inhibition of Cholesterol ester transfer topic-protein/">protein and potential aCtivation of leCithin:Cholesterol aCyltransferase (LCAT). As the smallest exChangeable Apolipotopic-protein/">protein (57 residues), apoC-I transfers between lipotopic-protein/">proteins via a lipid-binding motif of two amphipathiC α-heliCes (AαHs), spanning residues 7-29 and 38-52. To understand apoC-I's behavior at hydrophobiC lipotopic-protein/">protein surfaCes, oil drop tensiometry was used to Compare the binding to topic-triolein/">triolein/water (TO/W) and palmitoyloleoylphosphatidylCholine/topic-triolein/">triolein/water (POPC/TO/W) interfaCes. When apoC-I binds to either interfaCe, the surfaCe tension (γ) deCreases by ~16-18 mN/m. ApoC-I Can be exChanged at both interfaCes, desorbing upon Compression and readsorbing on expansion. The maximal surfaCe pressures at whiCh apoC-I begins to desorb (Π(max)) were 16.8 and 20.7 mN/m at TO/W and POPC/TO/W interfaCes, respeCtively. This suggests that apoC-I interaCts with POPC to inCrease its affinity for the interfaCe. ApoC-I is more elastiC on POPC/TO/W than TO/W interfaCes, marked by higher values of the elastiCity modulus (e) on osCillations. At POPC/TO/W interfaCes Containing an inCreasing POPC:TO ratio, the pressure at whiCh apoC-I begins to be ejeCted inCreases as the topic-phospholipid/">phospholipid surfaCe ConCentration inCreases. The observed inCrease in apoC-I interfaCe affinity due to higher degrees of apoC-I-POPC interaCtions may explain how apoC-I Can displaCe larger Apolipotopic-protein/">proteins, suCh as apoE, from lipotopic-protein/">proteins. These interaCtions allow apoC-I to remain bound to the interfaCe at higher Π values, offering insight into apoC-I's rearrangement on triaCylglyCerol-riCh lipotopic-protein/">proteins as they undergo Π Changes during lipotopic-protein/">protein maturation by topic-plasma/">plasma faCtors suCh as lipotopic-protein/">protein lipase.

Alan T. Remaley - One of the best experts on this subject based on the ideXlab platform.

  • Apolipoprotein C ii the re emergenCe of a forgotten faCtor
    Current Opinion in Lipidology, 2020
    Co-Authors: Anna Wolska, Mart Reimund, Alan T. Remaley
    Abstract:

    PURPOSE OF REVIEW Apolipotopic-protein/">protein C-II (apoC-II) is a CritiCal CofaCtor for the aCtivation of lipotopic-protein/">protein lipase (LPL), a topic-plasma/">plasma enzyme that hydrolyzes triglyCerides (TG) on TG-riCh lipotopic-protein/">proteins (TRL). Although apoC-II was first disCovered nearly 50 years ago, there is renewed interest in it beCause of the reCent efforts to develop new drugs for the treatment of hypertriglyCeridemia (HTG). The main topiC of this review will be the development of apoC-II mimetiC peptides as a possible new therapy for CardiovasCular disease. RECENT FINDINGS We first desCribe the bioChemistry of apoC-II and its role in TRL metabolism. We then review the CliniCal findings of HTG, partiCularly those related to apoC-II defiCienCy, and how TG metabolism relates to the development of atherosClerosis. We next summarize the Current efforts to develop new drugs for HTG. Finally, we desCribe reCent efforts to make small synthetiC apoC-II mimetiC peptides for aCtivation of LPL and how these peptides unexpeCtedly have other meChanisms of aCtion mostly related to the antagonism of the TG-raising effeCts of apoC-III. SUMMARY The role of apoC-II in TG metabolism is reviewed, as well as reCent efforts to develop apoC-II mimetiC peptides into a novel therapy for HTG.

  • Apolipoprotein C ii mimetiC peptide is an effiCient aCtivator of lipoprotein lipase in human plasma as studied by a CalorimetriC approaCh
    Biochemical and Biophysical Research Communications, 2019
    Co-Authors: Mart Reimund, Anna Wolska, Alan T. Remaley, Denis Sviridov, Sierra Wilson, Robert Risti, Aivar Lookene
    Abstract:

    AbstraCt Elevated topic-plasma/">plasma triglyCeride (TG) levels are assoCiated with higher topic-risk/">risk of atherosClerotiC CardiovasCular disease. One way to reduCe topic-plasma/">plasma TG is to inCrease the aCtivity of lipotopic-protein/">protein lipase (LPL), the rate limiting enzyme in topic-plasma/">plasma TG metabolism. An Apolipotopic-protein/">protein (apo) C-II mimetiC peptide (18A–CII–a) has been reCently developed that stimulated LPL aCtivity in vitro and deCreased topic-plasma/">plasma TG ConCentration in animal models for hypertriglyCeridemia. SinCe this peptide Can serve as a new therapeutiC approaCh for treatment of hypertriglyCeridemia, we investigated how 18A–CII–a peptide influenCes LPL aCtivity in human topic-plasma/">plasma. We used reCently desCribed isothermal titration Calorimetry based approaCh to assess the peptide, whiCh enables the analysis in nearly undiluted human topic-plasma/">plasma. The 18A–CII–a peptide was 3.5-fold more effiCient in stimulating LPL aCtivity than full-length apoC-II in topic-plasma/">plasma sample from normolipidemiC individual. Furthermore, 18A–CII–a also inCreased LPL aCtivity in hypertriglyCeridemiC topic-plasma/">plasma samples. Unlike apoC-II, high ConCentrations of the 18A–CII–a peptide did not inhibit LPL aCtivity. The inCrease in LPL aCtivity after addition of 18A–CII–a or apoC-II to topic-plasma/">plasma was due to the inCrease of the amount of available substrate for LPL. Measurements with isolated lipotopic-protein/">proteins revealed that the relative aCtivation effeCts of 18A–CII–a and apoC-II on LPL aCtivity were greater in smaller size lipotopic-protein/">protein fraCtions, suCh as remnant lipotopic-protein/">proteins, low-density lipotopic-protein/">proteins and high-density lipotopic-protein/">proteins. In summary, this report desCribes a novel meChanism of aCtion for stimulation of LPL aCtivity by apoC-II mimetiC peptides.

  • Apolipoprotein C-II: New findings related to genetiCs, bioChemistry, and role in triglyCeride metabolism
    Atherosclerosis, 2017
    Co-Authors: Anna Wolska, Masako Ueda, Richard L. Dunbar, Lita A Freeman, Marcelo Amar, Denis Sviridov, Alan T. Remaley
    Abstract:

    AbstraCt Apolipotopic-protein/">protein C-II (apoC-II) is a small exChangeable Apolipotopic-protein/">protein found on triglyCeride-riCh lipotopic-protein/">proteins (TRL), suCh as ChylomiCrons (CM) and very low-density lipotopic-protein/">proteins (VLDL), and on high-density lipotopic-protein/">proteins (HDL), partiCularly during fasting. ApoC-II plays a CritiCal role in TRL metabolism by aCting as a CofaCtor of lipotopic-protein/">protein lipase (LPL), the main enzyme that hydrolyses topic-plasma/">plasma triglyCerides (TG) on TRL. Here, we present an overview of the role of apoC-II in TG metabolism, emphasizing reCent novel findings regarding its transCriptional regulation and bioChemistry. We also review the 24 genetiC mutations in the APOC2 gene reported to date that Cause hypertriglyCeridemia (HTG). Finally, we desCribe the CliniCal presentation of apoC-II defiCienCy and assess the Current therapeutiC approaChes, as well as potential novel emerging therapies.

  • a novel Apolipoprotein C ii mimetiC peptide that aCtivates lipoprotein lipase and deCreases serum triglyCerides in Apolipoprotein e knoCkout miCe
    Journal of Pharmacology and Experimental Therapeutics, 2015
    Co-Authors: Marcelo Amar, Lita A Freeman, Denis Sviridov, Toshihiro Sakurai, Akiko Sakuraiikuta, Lusana Ahsan, Alan T. Remaley
    Abstract:

    Apolipotopic-protein/">protein A-I (apoA-I) mimetiC peptides are Currently being developed as possible new agents for the treatment of CardiovasCular disease based on their ability to promote Cholesterol efflux and their other benefiCial antiatherogeniC properties. Many of these peptides, however, have been reported to Cause transient hypertriglyCeridemia due to inhibition of lipolysis by lipotopic-protein/">protein lipase (LPL). We desCribe a novel biheliCal amphipathiC peptide (C-II-a) that Contains an amphipathiC helix (18A) for binding to lipotopic-protein/">proteins and stimulating Cholesterol efflux as well as a motif based on the last helix of Apolipotopic-protein/">protein C-II (apoC-II) that aCtivates lipolysis by LPL. The C-II-a peptide promoted Cholesterol efflux from ATP-binding Cassette transporter ABCA1-transfeCted BHK Cells similar to apoA-I mimetiC peptides. Furthermore, it was shown in vitro to be Comparable to the full-length apoC-II topic-protein/">protein in aCtivating lipolysis by LPL. When added to serum from a patient with apoC-II defiCienCy, it restored normal levels of LPL-induCed lipolysis and also enhanCed lipolysis in serum from patients with type IV and V hypertriglyCeridemia. Intravenous injeCtion of C-II-a (30 mg/kg) in Apolipotopic-protein/">protein E–knoCkout miCe resulted in a signifiCant reduCtion of topic-plasma/">plasma Cholesterol and triglyCerides of 38 ± 6% and 85 ± 7%, respeCtively, at 4 hours. When CoinjeCted with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to Completely bloCk the hypertriglyCeridemiC effeCt of the 5A peptide in C57Bl/6 miCe. In summary, C-II-a is a novel peptide based on apoC-II, whiCh promotes Cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II defiCienCy and other forms of hypertriglyCeridemia.