Abstract 632: Lipoprotein Lipase Activators: A New Potent Drug Class for Treatment of Dyslipidemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Madelene Ericsson ◽  
Mikael Larsson ◽  
Remi Caraballo ◽  
Per-Anders Enquist ◽  
Mikael Elofsson ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
De Novo ◽  
Plasma Lipid ◽  
Hdl Cholesterol ◽  
Residual Risk ◽  
Lipid Response ◽  
Low Hdl ◽  
Specific Tissue ◽  
Potent Drug ◽  
Subcutaneous Adipose

Aim: Elevated plasma TG and low HDL-cholesterol are part of CVD residual risk. Lipoprotein lipase (LPL) is the central enzyme controlling plasma TG hydrolysis and affecting de novo HDL formation. Thus LPL is an attractive target for correcting dyslipidemia and reduction of CVD residual risk. We have identified a novel first-in-class small molecule LPL activator - LP071. The objective with this study was to characterize the plasma lipid metabolism in LPL activator treated mice. Methods: ApoE3L:CETP mice were treated week with LP071. Plasma lipid profiles were analyzed using FPLC fractioning. LPL activity was investigated systemically and in specific tissue. Using triton WR1339 blockade chylomicron and VLDL secretion were assessed. Functional lipid clearance test were performed by oral fat tolerance tests. Results: Fasting plasma TG levels decreased with 97 % in apoE3L:CETP mice treated with LP071; HDL-c were increased by 116 % and (V)LDL-c were decreased with 91 %. Plasma free glycerol and NEFA were significantly lowered, 26 % and 22 % respectively. After an oral lipid load the plasma lipid response was significantly blunted in LP071 treated mice compared to controls. LPL activity in subcutaneous adipose tissue was increased 1500 % and in BAT LPL was increased by 100% at 3 h after a lipid gavage in WT mice treated with LP071. Conclusions: LP071 is a potent compound that can improve plasma lipid levels to a less atherogenic profile. The LP-class LPL activators can potentially help battle CVD residual risk in the future.

scholarly journals Favourable impact of low-calorie cranberry juice consumption on plasma HDL-cholesterol concentrations in men

2006 ◽  
Vol 96 (2) ◽  
pp. 357-364 ◽  
Author(s):  
Guillaume Ruel ◽  
Sonia Pomerleau ◽  
Patrick Couture ◽  
Simone Lemieux ◽  
Benoît Lamarche ◽  
...  
Keyword(s):  
Multivariate Analyses ◽  
Plasma Lipid ◽  
Hdl Cholesterol ◽  
Polyphenolic Compounds ◽  
Cholesterol Concentration ◽  
Cranberry Juice ◽  
Low Calorie ◽  
Vldl Cholesterol ◽  
Low Hdl ◽  
Metabolic Variables

A low HDL-cholesterol concentration is an independent risk factor for CVD. Studies have suggested that flavonoid consumption may be cardioprotective, and a favourable impact on circulating HDL-cholesterol concentrations has been suggested to partially explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on the plasma lipid profile of abdominally obese men. For that purpose, thirty men (mean age 51 (SD 10) years) consumed increasing doses of CJC during three successive periods of 4 weeks (125ml/d, 250ml/d, 500ml/d). Before the study and after each phase, we measured changes in physical and metabolic variables. We noted a significant increase in plasma HDL-cholesterol concentration after the consumption of 250ml CJC/d (+8·6±14·0% v. 0ml CJC/d; P<0·01), an effect that plateaued during the last phase of the study (500ml CJC/d: +8·1±10·0% v. 0ml CJC/d; P<0·0001). Multivariate analyses revealed that changes in plasma apo A-I (IR2=48%, P<0·0001) and triacylglycerol (R2=16%, P<0·005) concentrations were the only variables significantly contributing to the variation in plasma HDL-cholesterol concentration noted in response to the intervention. No variation was observed in total as well as in LDL and VLDL cholesterol. The present results show that daily CJC consumption is associated with an increase in plasma HDL-cholesterol concentrations in abdominally obese men. We hypothesise that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can be cardioprotective.

scholarly journals A specific plasma lipid signature associated with high triglycerides and low HDL cholesterol identifies residual CAD risk in patients with chronic coronary syndrome

2021 ◽  
Author(s):  
Nicoletta Di Giorgi ◽  
Elena Michelucci ◽  
Jeff M. Smit ◽  
Arthur J.H.A. Scholte ◽  
Mohammed El Mahdiui ◽  
...  
Keyword(s):  
Plasma Lipid ◽  
Hdl Cholesterol ◽  
Coronary Syndrome ◽  
Low Hdl ◽  
Cad Risk

Common genetic variants that relate to disorders of lipid transport in Spanish subjects with premature coronary artery disease

2001 ◽  
Vol 100 (2) ◽  
pp. 183-190 ◽  
Author(s):  
Ll. MASANA ◽  
G. FEBRER ◽  
J. CAVANNA ◽  
M. G. BARONI ◽  
W. MARZ ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lipoprotein Lipase ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Transport ◽  
Premature Coronary Artery Disease ◽  
Artery Disease

Fifteen common polymorphic variants at six loci (apolipoproteins AI, B, CIII and E, hepatic lipase and lipoprotein lipase) involved in plasma lipid transport have been studied in 210 northern Spanish men, of whom 98 had proven coronary artery disease. The other 112 men were clinically free from coronary artery disease and acted as controls. The genotypes were investigated for relationships with plasma lipid and lipoprotein levels, as well as for the presence of coronary artery disease. As expected, the mean levels of plasma triacylglycerols (triglycerides) and lipoprotein (a) and the number of smokers were significantly higher in the disease group, and high-density lipoprotein (HDL)-cholesterol was significantly lower. Surprisingly, plasma cholesterol and low-density lipoprotein cholesterol were not different between the two groups. With regard to the common mutations, plasma triacylglycerol levels were related to the HindIII variants of lipoprotein lipase (P < 0.05), to the apolipoprotein CIII variant (C3175G in exon 4) and to the apolipoprotein AI XmnI polymorphisms (P < 0.05 and P < 0.02 respectively). The apolipoprotein E variants were related to plasma cholesterol (P < 0.05), HDL-cholesterol (P < 0.02), plasma triacylglycerols (P < 0.05) and the triacylglycerol/HDL ratio (P < 0.01). Only the three-codon insertion/deletion variants of the apolipoprotein B signal peptide region discriminated between the two groups with or without arterial disease (P = 0.02). The possible functional effects of these common mutations are discussed.

scholarly journals Low HDL and high triglycerides predict COVID-19 severity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lluís Masana ◽  
◽  
Eudald Correig ◽  
Daiana Ibarretxe ◽  
Eva Anoro ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Plasma Lipid ◽  
Hdl Cholesterol ◽  
Cross Sectional Study ◽  
Infection Process ◽  
Plasma Lipid Profile ◽  
Cross Sectional ◽  
Cholesterol Levels ◽  
Atherogenic Dyslipidaemia ◽  
Low Hdl

AbstractLipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.

The correlation between lipid metabolism disorders and the prostate cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Justyna Dłubek ◽  
Jacek Rysz ◽  
Zbigniew Jabłonowski ◽  
Anna Gluba-Brzózka ◽  
Beata Franczyk
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Cancer Progression ◽  
De Novo ◽  
Prostate Gland ◽  
Hdl Cholesterol ◽  
Atp Citrate Lyase ◽  
Male Population ◽  
Lipid Metabolism Disorders

: Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.

Ser447stopMutation in Lipoprotein Lipase Is Associated With Elevated HDL Cholesterol Levels in Normolipidemic Males

1997 ◽  
Vol 17 (3) ◽  
pp. 595-599 ◽  
Author(s):  
Jan Albert Kuivenhoven ◽  
Björn E. Groenemeyer ◽  
Jolanda M. A. Boer ◽  
Paul W. A. Reymer ◽  
Riteke Berghuis ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Hdl Cholesterol ◽  
Cholesterol Levels
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