Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects

Leança, Camila Canteiro; Nunes, V.S.; Panzoldo, Natália Baratella; Zago, Vanessa Helena de Souza; Parra, Eliane Soler; Cazita, P.M.; Jauhiainen, Matti; Passarelli, Marisa; Nakandakare, Edna Regina; Faria, Eliana Cotta de; Quintão, Eder Carlos Rocha

doi:10.1186/1475-2840-12-173

Cited by 20 publications

(20 citation statements)

References 46 publications

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“…The most important antiatherogenic function of HDL is reverse cholesterol transport [120]. HDL also exhibits other potential cardioprotective functions such as anti-oxidative, anti-inflammatory and endothelium-dependent vasodilatory effects [121][122][123].…”

Section: Tg and Hdlmentioning

confidence: 99%

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Tenenbaum

Klempfner

Fisman

2014

Cardiovasc Diabetol

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The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

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Section: Tg and Hdlmentioning

confidence: 99%

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Tenenbaum

Klempfner

Fisman

2014

Cardiovasc Diabetol

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“…In this regard LCAT activity is higher in individuals with low HDL-C plasma concentration and the CETP activity does not differ between individuals with low and high plasma HDL-C levels [14]. VLDL transports less than 20% of NCSPCS.…”

Section: Discussionmentioning

confidence: 83%

Plasma distribution of non-cholesterol sterols precursors of cholesterol synthesis and phytosterols depend on HDL concentration

Nunes¹,

Silva²,

Ferreira³

et al. 2020

Preprint

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Background Because several sterols are carried by serum lipoproteins that are pivotal in cholesterol metabolism and atherosclerosis this study aimed at investigating their lipoprotein distribution in individuals differing according to HDL-C plasma levels. Methods Healthy participants were selected with plasma HDL-C concentrations < 40 mg/dL (Low HDL, n = 12), above 40 mg/dL and below 60 mg/dL (Controls, n = 10), or above 60 mg/dL (High HDL, n = 15). Plasma lipoproteins were separated by sequential ultracentrifugation. [27-OHC]), noncholesterol sterols precursors of cholesterol synthesis (NCSPCS: desmosterol and lathosterol) and phytosterols (campesterol and sitosterol) were measured by GC-MS analysis. Diferences between groups were compared by Kruskall-walys and Dunn's post-test with correction by Bonferroni. Results The groups were similar in about BMI, age, gender distribution and blood glucose, total cholesterol and LDL-C. The High HDL group had lower concentrations of triglycerides and VLDL-C compared to others. Percentage distribution of plasma 24-OHC and 27-OHC in lipoproteins did not differ among investigated groups, but plasma concentration of 24-OHC was lower in High HDL than in Low HDL (27- OHC significance difference was borderline). NCSPCS and phytosterols predominate in LDL, which carries approximately 50% of these molecules. Approximately 30% of desmosterol and lathosterol are present in HDL, the High HDL group carrying higher percent of both sterols than the Low HDL and Control groups. Less than 20% of NCSPCS are transported in VLDL. Concentration of plasma campesterol and sitosterol did not differ among groups. However, LDL sitosterol percent distribution is lower in High HDL than in Low HDL and Controls. Campesterol and sitosterol percent distributions are higher in High HDL than in the Low HDL group. Conclusions Elevated NCSPCS in the High HDL group suggests HDL facilitates the export of these sterols from cells but not the export of the cholesterol metabolite 24-OHC which is lower in the High HDL than in the Low HDL group. Percent campesterol and sitosterol elevated in HDL suggests phytosterols absorbed in the enterocytes are incorporated mostly into the nascent HDL.

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“…In addition, HDL particle size and volume were significantly lower, indicating a possible increase in HDL catabolism. Previous findings from our group in another cohort of healthy, normal weight individuals, demonstrated that plasma HDL-C variations are related to several parameters controlling plasma lipoprotein metabolism and to the degree of insulin sensitivity (Leanca et al, 2013). In fact, the isolated low HDL-C is commonly found with hyperinsulinism, without hypertriglyceridemia or other lipoprotein variations (Rashid et al, 2003;Karhapaa et al, 1994).…”

Section: Discussionmentioning

confidence: 93%

Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells

Scherrer

Zago

Parra

et al. 2015

Gene

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Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects

Cited by 20 publications

References 46 publications

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Plasma distribution of non-cholesterol sterols precursors of cholesterol synthesis and phytosterols depend on HDL concentration

Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells

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