Obesity-related Changes in High-density Lipoprotein Metabolism

Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida, USA.
Obesity (Impact Factor: 3.73). 07/2008; 16(6):1152-60. DOI: 10.1038/oby.2008.202
Source: PubMed


Obesity is associated with a 3-or-more-fold increase in the risk of fatal and nonfatal myocardial infarction (1,2,3,4,5,6). The American Heart Association has reclassified obesity as a major, modifiable risk factor for coronary heart disease (7). The increased prevalence of premature coronary heart disease in obesity is attributed to multiple factors (8,9,10). A principal contributor to this serious morbidity is the alterations in plasma lipid and lipoprotein levels. The dyslipidemia of obesity is commonly manifested as high plasma triglyceride levels, low high-density lipoprotein cholesterol (HDLc), and normal low-density lipoprotein cholesterol (LDLc) with preponderance of small dense LDL particles (7,8,9,10). However, there is a considerable heterogeneity of plasma lipid profile in overweight and obese people. The precise cause of this heterogeneity is not entirely clear but has been partly attributed to the degree of visceral adiposity and insulin resistance. The emergence of glucose intolerance or a genetic predisposition to familial combined hyperlipidemia will further modify the plasma lipid phenotype in obese people (11,12,13,14,15).

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    • "Cardiovascular disease is the main cause of morbidity and mortality in individuals with metabolic syndrome (MetS) [1]. Cardiovascular disease risk factors (CVR) include an excess of body fat, promoting dyslipidemia, with reduced high-density lipoprotein cholesterol (HDL) and increased low-density lipoprotein cholesterol (LDL) [2]. A low level of HDL is regarded as a sensitive discriminator of atherogenicity and is one among the five criteria selected by the International Diabetes Federation (IDF) to characterize MetS [3]. "
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    ABSTRACT: BackgroundWe aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) – a surrogate indicator of atherogenesis.Methods100 participants (50–70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint® electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured.Results78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Using a generalized estimating equations model, none of the subfractions of lipoproteins nor apolipoproteins were linked to CIMT.ConclusionsLipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions.Trial registrationNCT00917917
    Lipids in Health and Disease 07/2014; 13(1). DOI:10.1186/1476-511X-13-112 · 2.22 Impact Factor
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    • "HDLc is cardioprotective due to its antioxidant, anti-inflammatory, and scavenging properties (Mooradian et al., 2008). HDLc has a complex metabolism, and elevated levels must be interpreted in context with the overall lipid profile (Mooradian et al., 2008). To our knowledge there has been no reported involvement of the orexin system in HDLc processing; the mechanism by which ACT-335827 affects HDLc metabolism warrants further examination. "
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    ABSTRACT: The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO) associated with metabolic syndrome (MetS). Rats were fed either standard chow (SC) or a cafeteria (CAF) diet comprised of intermittent human snacks and a constant free choice between a HF/sweet (HF/S) diet and SC for 13 weeks. Thereafter the SC group was treated with vehicle (for 4 weeks) and the CAF group was divided into a vehicle and an ACT-335827 treatment group. Energy and water intake, food preference, and indicators of MetS (abdominal obesity, glucose homeostasis, plasma lipids, and blood pressure) were monitored. Hippocampus-dependent memory, which can be impaired by DIO, was assessed. CAF diet fed rats treated with ACT-335827 consumed less of the HF/S diet and more of the SC, but did not change their snack or total kcal intake compared to vehicle-treated rats. ACT-335827 increased water intake and the high-density lipoprotein associated cholesterol proportion of total circulating cholesterol. ACT-335827 slightly increased body weight gain (4% vs. controls) and feed efficiency in the absence of hyperphagia. These effects were not associated with significant changes in the elevated fasting glucose and triglyceride (TG) plasma levels, glucose intolerance, elevated blood pressure, and adiposity due to CAF diet consumption. Neither CAF diet consumption alone nor ACT-335827 affected memory. In conclusion, the main metabolic characteristics associated with DIO and MetS in rats remained unaffected by chronic ACT-335827 treatment, suggesting that pharmacological OXR-1 blockade has minimal impact in this model.
    Frontiers in Pharmacology 12/2013; 4:165. DOI:10.3389/fphar.2013.00165 · 3.80 Impact Factor
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    • "On the other hand, some key enzymes involved in HDL metabolism, such as CETP, LCAT, hepatic lipase(HL) and protein phospholipid transfer protein(PLTP), are changed in obese people with insulin resistance, promoting this process [28]. What's more, the increased plasma clearance of apoA-I and downregulation of its production also offer some contributions to the reduction of HDL-C [29]. In spite of these interpretations, there is no consolidated explanation for the association between obesity and decreased HDL-C levels. "
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    ABSTRACT: Obesity, a significant risk factor for various chronic diseases, is universally related to dyslipidemia mainly represented by decreasing high-density lipoprotein cholesterol (HDL-C), which plays an indispensible role in development of cardiovascular disease (CVD). However, the mechanisms underlying obesity and low HDL-C have not been fully elucidated. Previous studies have focused on the alteration of HDL catabolism in circulation following elevated triglyceride (TG). But recent findings suggested that liver and fat tissue played pivotal role in obesity related low HDL-C. Some new molecular pathways like microRNA have also been proposed in the regulation of HDL metabolism in obesity. This article will review recent advances in understanding of the potential mechanism of low HDL-C in obesity.
    Lipids in Health and Disease 10/2011; 10(1):176. DOI:10.1186/1476-511X-10-176 · 2.22 Impact Factor
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