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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary hyperlipoproteinemias are found in connection with other primary organic diseases. Typical examples are those seen with diabetes mellitus, liver and kidney diseases. In addition there are changes induced by hormonal dysfunctions such as hypothyroidism, by the use of oral contraceptives or in postmenopausal women. During pregnancy there is a physiological transient increase in lipoproteins. In addition to primary organic diseases there are a number of exogenous factors such as obesity, malnutrition and alcohol abuse causing hyperlipidemia. The relation between hypertension and hyperlipidemia described as familial dyslipidemic hypertension is less well known. Obesity, hypertension, dyslipidemia, hyperuricemia and impaired glucose tolerance are the basic conditions of the metabolic syndrome. Familial combined hyperlipidemia is a genetically determined, dyslipidemic syndrome with a high prevalence among patients with coronary artery disease and stroke. As there are some links between familial combined hyperlipidemia and secondary hyperlipoproteinemias, this disease entity is discussed together in this paper. Familial combined hyperlipidemia is metabolically, genetically and by this on a molecular level closely linked to familial dyslipidemic hypertension as well as the metabolic syndrome. The exact mechanism of this disease is currently unknown.
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PMID:[Secondary disorders of lipid metabolism, metabolic syndrome and familial combined hyperlipidemia]. 865 Sep 33

Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid disorders. Resistance of adipocytes to the effects of acylation stimulating protein (ASP) may contribute to ineffective triglyceride synthesis and thereby prolonged postprandial lipemia and increased fatty acid flux to the liver seen in FCHL patients. Interestingly, ASP is identical to C3a-desArg, fragment of the third component of complement. We examined the relationships between serum levels of complement components C3 and C4 and markers of lipid and glucose metabolism in 11 large FCHL families (n = 53). Median serum C3 levels were 38% higher in affected compared to non-affected male FCHL family members (1.90 g/l vs. 1.38, P = 0.0027). The strongest correlations were observed between serum complement C3 and apolipoprotein B levels, reaching 0.77 in males. These relations were not confounded by obesity or impaired glucose tolerance. In conclusion, serum levels of the main complement components C3 and C4 correlated significantly with serum lipid levels. Further studies are needed to clarify the importance of disturbances in the complement system on the pathogenesis of FCHL and other lipid disorders.
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PMID:Serum complement and familial combined hyperlipidemia. 962 89

Much has recently been learned about the processes involved in postprandial triacylglycerol clearance. As discussed previously, important differences in the metabolism of chylomicrons and VLDL have become apparent. The ASP pathway has also been recognized and appears to play a critical role in chylomicron metabolism. The ASP pathway is activated in order to trap the fatty acids released from chylomicrons by the action of LPL and there is now unequivocal in vivo evidence in human subjects that ASP is generated by adipocytes in the postprandial period. These findings match the in vitro data showing that chylomicrons, but not the other plasma lipoproteins or fatty acids, activate the generation of ASP by cultured human adipocytes. An inverse relationship appears to exist between the proportion of fatty acids taken up by adipocytes and that released into the general circulation. Too great a release into the general circulation because of diminished trapping of fatty acids released from chylomicrons appears to be critical in the pathogenesis of the dyslipoproteinaemias associated with hyperapo B or FCHL and omental obesity. Evidence has been presented that dysfunction of the ASP pathway may be one of the causes of this disorder. Put differently, the ASP pathway is essential for the normal clearance and disposition of dietary fatty acids. Binding of chylomicrons to capillary endothelium followed by lipolysis by LPL results in the sudden liberation of fatty acids, and in the marked generation of ASP by adipocytes. The ASP that is generated is essential if LPL is to continue to form fatty acids at a normal rate. It is essential also if the fatty acids which are formed are to enter the adipocyte rather than exit into the general circulation. The transport vehicle, the chylomicron, therefore stimulates the formation of the peptide, ASP, which is responsible for its successful metabolism. Thus, the ASP pathway provides the metabolic coordination between the chylomicron and the adipocyte, which we describe as microenvironmental metabolic regulation and which we believe is essential for the normal clearance of dietary triacylglycerol from plasma.
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PMID:The acylation-stimulating protein pathway and regulation of postprandial metabolism. 926 20

Familial combined hyperlipidemia (FCHL) is one of the most common familial dyslipidemias associated with premature heart disease. Subjects with FCHL typically have elevated apolipoprotein B (apoB) levels, variable elevations in cholesterol and/or triglycerides, and a predominance of small, dense, low density lipoprotein particles. It is thought that insulin resistance is important in the expression of the combined hyperlipidemia phenotype. To further characterize the relationship between insulin resistance and increased apoB levels, 11 subjects from well-characterized FCHL families and normal control subjects matched for weight and/or age underwent measurement of intra-abdominal fat (IAF) and subcutaneous fat (SQF) by CT scan, insulin sensitivity (Si) by the frequently sampled intravenous glucose tolerance test, and lipoprotein levels. Body mass index and IAF were higher and Si was lower (more insulin resistant) in the FCHL group than in the age-matched group, but the values were similar in the FCHL group and the age- and weight-matched control group. When the relationship between body fat distribution and Si was tested with multiple linear regression, only IAF was significantly correlated with Si after the addition of SQF and body mass index as independent variables. For any level of insulin sensitivity or IAF, however, apoB levels remained higher in the FCHL subjects than in the control groups. In conclusion, in FCHL, visceral obesity is an important determinant of insulin resistance. Visceral obesity and insulin resistance, however, do not fully account for the elevated levels of apoB in this disorder, and this study provides physiological support for separate, but additive, genetic determinants in the etiology of the lipid phenotype.
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PMID:Relationship of insulin sensitivity and ApoB levels to intra-abdominal fat in subjects with familial combined hyperlipidemia. 1130 74

Familial combined hyperlipidemia (FCH), a common cause of premature coronary artery disease, is genetically complex and poorly understood. Recently, a major locus on chromosome 1q21-23 exhibiting highly significant linkage was identified in Finnish FCH families by use of a parametric analysis. We now report highly significant evidence of linkage (maximum LOD score 3.8, recombination fraction 0) of an important FCH phenotype, elevated apolipoprotein B (apoB) levels, to a distinctly separate locus on chromosome 1p31 in Dutch pedigrees. ApoB is the major protein on very low density and low density lipoproteins, and elevated apoB levels have been used as a surrogate trait for FCH. Additional microsatellite markers in the 1p31 region were genotyped, and evidence of linkage improved (maximum LOD score 4.7) in a multipoint analysis of two markers in the peak region. The leptin receptor gene resides within this locus and is involved in obesity and insulin/glucose homeostasis. However, there was no evidence of an association between leptin receptor and apoB levels, raising the possibility that another gene on this chromosomal region contributes to elevated apoB levels in this Dutch population. This is one of the first loci identified for apoB levels in humans and is the second major locus implicated in the genetic etiology of FCH.
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PMID:Locus for elevated apolipoprotein B levels on chromosome 1p31 in families with familial combined hyperlipidemia. 1198 95

It is not easy to make diagnose FCHL in children, since a clear expression of lipoprotein abnormality is unlikely and standard criteria have not yet been established. We investigated eight cases of childhood FCHL and their families with respect to familial history, anthropometric parameters and serum lipoprotein levels, to explore the characteristics of childhood FCHL. To diagnose childhood FCHL it is necessary to clarify both the family history and lipid profiles of the parents. In this study, two prominent features were suggested; that serum TG level is affected by both obesity and age, and also in particular, that a significantly elevated level of serum apoB is a predominant feature of FCHL in childhood. It was found that hyperapoB may be revealed antecedently without other lipid abnormalities at an early age. Regardless of other lipoprotein abnormality, it was suggested that hyperapoB might be added to the early diagnostic criteria for FCHL.
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PMID:Familial combined hyperlipidemia (FCHL) in children: the significance of early development of hyperapoB lipoproteinemia, obesity and aging. 1256 May 93

Familial combined hyperlipidemia (FCH) is the most common inherited hyperlipidemia in humans, affecting 1 to 3% of the adult population and up to 20% of patients with premature myocardial infarction. FCH is traditionally diagnosed by total plasma cholesterol and/or triglyceride levels above the 90th percentile adjusted for age and gender; however, the diagnosis of FCH based on these diagnostic criteria is inconsistent in 26% of the subjects over a five-year period, emphasizing the need for re-evaluation of the diagnostic criteria for FCH. Recently, a nomogram was developed based on absolute apolipoprotein B levels in combination with triglyceride and total cholesterol levels adjusted for both age and gender to simply and accurately diagnose FCH. When percentiles of triglyceride and total cholesterol adjusted for age and gender are not available in a population, the definition of FCH can be established based on hypertriglyceridemia (> 1.5 mmol/l) and hyperapoB (> 1200 mg/l). Standardized and simple diagnostic criteria are necessary to further delineate the pathogenesis of FCH. Several metabolic pathways have been suggested to be important in causing the FCH phenotype including hepatic VLDL overproduction either with or without impaired clearance of triglyceride-rich lipoproteins from plasma. The presence of insulin resistance and obesity in FCH patients further contribute to the expression of the lipidphenotype. A disturbed adipose tissue metabolism that results in an increased plasma free fatty acid pool may be the culprit in the pathogenesis of FCH.
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PMID:Diagnostic criteria in relation to the pathogenesis of familial combined hyperlipidemia. 1563 Jun 32

Familial combined hyperlipidemia (FCH) is characterized by increased levels of total cholesterol, triglycerides, and/or apolipoprotein B. Other features of FCH are obesity and insulin resistance. Adiponectin is a secretory product of the adipose tissue. Low levels of adiponectin are associated with insulin resistance and accelerated atherosclerosis. The aim of this study was to determine whether decreased adiponectin levels are associated with FCH and its phenotypes. The study population comprised 644 subjects, including 158 patients with FCH. Serum adiponectin levels were determined using a commercially available ELISA. For both males and females, the mean adiponectin level (microg/ml) was significantly lower in FCH patients [2.0 (1.8-2.2) and 2.5 (2.3-2.8), respectively] compared with normolipidemic relatives [2.3 (2.2-2.5) and 3.1 (2.8-3.3), respectively] and spouses [2.4 (2.1-2.7) and 3.2 (2.8-3.6), respectively]. These differences remain significant after adjusting for waist circumference and insulin resistance. Low adiponectin level in FCH patients was a superior independent predictor of the atherogenic lipid profile, including high triglyceride levels, low HDL-cholesterol levels, and the amount of small, dense LDL present, compared with both obesity and insulin resistance. Low adiponectin levels may contribute to the atherogenic lipid profile in FCH, independent of insulin resistance and obesity, as measured by waist circumference. This finding implies a role of adipose tissue metabolism in the pathophysiology of FCH.
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PMID:Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile. 1610 49

Familial combined hyperlipidemia (FCH) is characterized by hypercholesterolemia and/or hypertriglyceridemia and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin levels have been associated with obesity, insulin resistance and CVD. The aim of this study was to determine whether increased leptin levels contribute to the FCH phenotype and its increased risk for CVD. The study population comprised 644 subjects, including 158 FCH patients. Leptin levels were determined, using a commercially available ELISA. For both males and females, the mean leptin level (ng/ml) was higher in FCH patients compared to normolipidemic relatives and spouses. However, after standardization for BMI and insulin resistance, these differences disappeared. The 90th percentile of the leptin level, standardized for BMI, insulin resistance and gender, was associated with an increased risk for CVD in FCH patients (odds ratio=2.9, 95% CI=1.1-8.0) and in non-FCH subjects (odds ratio=3.4, 95% CI=1.3-9.0). The overall increased risk for CVD, associated with a leptin level >90th percentile, was 3.3 (95% CI=1.7-6.4). We conclude that in patients with FCH, leptin levels are increased in proportion to their higher BMI and the presence of insulin resistance. These increased leptin levels are associated with an increased risk for CVD both in FCH patients and non-FCH subjects, independent of BMI, insulin resistance and gender.
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PMID:Elevated leptin levels in subjects with familial combined hyperlipidemia are associated with the increased risk for CVD. 1628 98

Postprandial hyperlipidaemia is a common metabolic disturbance in atherosclerosis. During the postprandial phase, chylomicrons and their remnants can penetrate the intact endothelium and cause foam cell formation. These particles are highly atherogenic after modification. People in the Western world are non-fasting for most of the day, which consequently leads to a continuous challenge of the endothelium by atherogenic lipoproteins and their remnants. Furthermore, atherosclerosis is considered a low-grade chronic inflammatory disease. Many studies have shown that the process of atherogenesis in part starts with the interaction between the activated leucocytes and activated endothelium. Postprandial lipoproteins can activate leucocytes in the blood and up-regulate the expression of leucocyte adhesion molecules on the endothelium, facilitating adhesion and migration of inflammatory cells into the subendothelial space. Another inflammatory process associated with postprandial lipaemia is the activation of the complement system. Its central component C3 has been associated with obesity, coronary sclerosis, the metabolic syndrome and fasting and postprandial TAGs (triacylglycerols). Moreover, chylomicrons are the strongest stimulators of adipocyte C3 production via activation of the alternative complement cascade. A postprandial C3 increment has been shown in healthy subjects and in patients with CAD (coronary artery disease) and with FCHL (familial combined hyperlipidaemia). Postprandial lipaemia has been related to TAG and free fatty acid metabolism. All of these mechanisms provide an alternative explanation for the atherogenicity of the postprandial period.
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PMID:Postprandial inflammation and endothelial dysfuction. 1751 29


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