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

During a fourteen-year-period 257 patients underwent carotid endarterectomy in an unselected population of 700,000 inhabitants. The incidence of haemodynamically significant restenosis was 13.5% in 133 vessels in 116 patients studied by duplex scanning 28 to 209 months following carotid endarterectomy. The most striking differences between patent and restenosed cases were in serum cholesterol, triglyceride and HDL-cholesterol levels. The patients with a long-term low cholesterol (less than 6.5 mmol/l), low triglyceride (less than 1.42 mmol/l) and high HDL cholesterol (greater than 1.0 mmol/l) levels had significantly less high grade restenosis (P less than 0.05). Apolipoprotein A-I and B had no significant effect, but if the lowest limit of normal apolipoprotein A-I level was considered as 1.27 g/l the difference was significant. The frequency of a high-grade restenosis in patients with diabetes mellitus and coronary heart disease was not significantly increased, but supports the view that these are risk factors in the development of atherosclerotic changes in an operated carotid artery. The incidence of recurrent stenosis appears to be unrelated to hypertension, claudication, obesity, smoking, operative factors or to the indication for surgery. Men were more prone than women to get a high-grade restenosis. Postoperative treatment with acetylsalicylic acid was most effective, the incidence was only half of that expected, whereas the anticoagulants or a combination of acetylsalicylic acid and dipyridamole were of no benefit. Haematocrit, RBC, platelet count and thrombocrit were contradictory.
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PMID:Late carotid restenosis: aetiologic factors for recurrent carotid artery stenosis during long-term follow-up. 274 59

Reports of increased susceptibility of persons from the Indian subcontinent to coronary heart disease led us to examine serum lipids and apolipoproteins in a group of physicians born in India now living in the U.S. A matched sample of U.S.-born physicians working at the same institution was recruited as controls. Fasting triglyceride (TG) levels were twice as high among the Indians (174 vs 86 mg/dl, P = 0.002), total cholesterol modestly increased (193 vs 177 mg/dl, P less than or equal to 0.01) and high density lipoprotein-cholesterol (HDL-C) fraction depressed 36 vs 40 mg/dl, P = 0.006). Both TG and HDL-C were strongly determined by relative obesity in the Americans, but not among the immigrants. Calculated values of low density lipoprotein-cholesterol (LDL-C) were similar in the two groups. Apolipoprotein A-I was significantly lower in a subsample of the Indians, while Apo B was higher. Minor differences between the groups in body mass index, food frequency intake, smoking patterns, alcohol intake and exercise did not significantly influence the results. Hereditary differences in lipid metabolism may have a role in these findings, however, the delayed effects of adaptation to U.S. lifestyle cannot be ruled out.
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PMID:Serum lipids of Indian physicians living in the U.S. compared to U.S.-born physicians. 309 38

Abnormalities of plasma high density lipoprotein (HDL) levels commonly reflect altered metabolism of the major HDL apolipoproteins, apoA-I and apoA-II, but the regulation of apolipoprotein metabolism is poorly understood. Two mouse models of obesity, ob/ob and db/db, have markedly increased plasma HDL cholesterol levels. The purpose of this study was to evaluate mechanisms responsible for increased HDL in ob/ob mice and to assess potential reversibility by leptin administration. ob/ob mice were found to have increased HDL cholesterol (2-fold), apoA-I (1.3-fold), and apoA-II (4-fold). ApoA-I mRNA was markedly decreased (to 25% of wild-type) and apoA-II mRNA was unchanged, suggesting a defect in HDL catabolism. HDL apoprotein turnover studies using nondegradable radiolabels confirmed a decrease in catabolism of apoA-I and apoA-II and a 4-fold decrease in hepatic uptake in ob/ob mice compared with wild-type, but similar renal uptake. Low dose leptin treatment markedly lowered HDL cholesterol and apoA-II levels in both ob/ob mice and in lean wild-type mice, and it restored apoA-I mRNA to normal levels in ob/ob mice. These changes occurred without significant alteration in body weight. Moreover, ob/ob neuropeptide Y-/- mice, despite marked attenuation of diabetes and obesity phenotypes, showed no change in HDL cholesterol levels relative to ob/ob mice. Thus, increased HDL levels in ob/ob mice reflect a marked hepatic catabolic defect for apoA-I and apoA-II. In the case of apoA-I, this is offset by decreased apoA-I mRNA, resulting in apoA-II-rich HDL particles. The studies reveal a specific HDL particle catabolic pathway that is down-regulated in ob/ob mice and suggest that HDL apolipoprotein turnover may be regulated by obesity and/or leptin signaling.
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PMID:Increased high density lipoprotein (HDL), defective hepatic catabolism of ApoA-I and ApoA-II, and decreased ApoA-I mRNA in ob/ob mice. Possible role of leptin in stimulation of HDL turnover. 993 8

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.
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PMID:Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan. 1020 80

Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis.
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PMID:New aspects in the pathogenesis of diabetic atherothrombosis. 1560 89

The analysis of plasma samples from healthy, diabetic and nephropathic subjects was carried out by 2D gel electrophoresis. This approach shows clear differences among the three classes of subjects. In the case of diabetic and nephropathic patients intense spots appear. Their enzymatic digestion followed by matrix assisted laser desorption ionization/mass spectrometry (MALDI/MS) analysis shows that an overexpression of unglycated and glycated ApoA-I is present in both pathological states. Interestingly, this trend is also observed for the retinol-binding protein (RBP). The data obtained can be relevant to assess possible risks associated either with the glycation level of ApoA-I or with the overexpression of RBP. In fact, in the former case possibly a different functionality of the glycated protein is to be expected, reflecting a different efficiency in cholesterol transport. In the latter case, the increase of RBP level can be related to the overweight of the diabetic subjects under investigation: it is known that obesity leads to RBP overexpression. In the case of nephropathic patients, the RBP level increases in parallel with serum creatinin.
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PMID:On the search for glycated lipoprotein ApoA-I in the plasma of diabetic and nephropathic patients. 1772 6

Atherosclerotic cardiovascular disease is a leading cause of morbidity and premature mortality in Western countries and dyslipidemia is a recognized major cardiovascular risk factor. Evidences demonstrate that the atherosclerotic process begins early in childhood. Children showing dyslipidemia, as well as other cardiovascular risk factors, including hypertension, overweight/obesity and diabetes mellitus, are defined at high risk. To identify these children a selective screening between 2 to 10 years of age is necessary. This program must be performed to those children showing a familiarity for primary dyslipidemia and/or precocious cardiovascular events. These subjects need to undergo lipid biochemical analysis and assessment of other emergent risk factors (as ApoB, ApoA-I and their ratio). Given that total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations vary by age and sex, the use of percentile values according to these parameters is now recommended. In these high-risk subjects the first step to lower LDL-C under the value of 130 mg/dL is represented by an appropriate physical activities and Step II diet. This entails further reduction of saturated fatty acid intake to less than 7% of daily calories and of cholesterol to less than 200 mg/day (since two years of age). When diet therapy is insufficient to lower LDL-C to the acceptable concentration, the use of non-pharmacologic agents (soluble fibers, plant stanols, sterols) is suggested. The third approach, for children showing persistent elevated LDL-C >95(th) percentile, is represented by drugs, that are allowed only in children older than eight years.
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PMID:Identification and management of dyslipidemic children. 1975 48

To compare the molecular composition and functional differences at the lipoprotein level, we analyzed individual lipoprotein fractions from male patients with metabolic syndrome (MetS) (n=10) and gender- and age-matched healthy controls (n=14). The MetS group had significantly higher obesity, blood pressure, serum cholesterol, triglyceride (TG), adiponectin, and uric acid levels than the control group, while the serum blood urea nitrogen and creatinine levels of the MetS group were in the normal range. The MetS group had much weaker serum antioxidant ability and were more susceptible to copper-mediated low-density lipoprotein (LDL)-oxidation. TG and apoC-III co-accumulated with LDL, high density lipoprotein (HDL)2, and HDL3 in the MetS group. The MetS group had serum amyloid A (SAA)-enriched HDL2 and HDL3, although the serum level of SAA was not higher than in controls. The MetS group had significantly deprived paraoxonase (PON) activity in the serum and HDL, while the MetS group had 38% higher serum cholesteryl ester transfer protein (CETP) activity than that of the control group. Many serum parameters, such as TG, apoC-III, and uric acid, were elevated in the MetS group, and most of these measures were enriched in the LDL and HDL fractions rather than the very low density lipoprotein (VLDL) fraction. The lipid and apolipoprotein composition of HDL was severely altered and its beneficial functions were severely diminished. ApoA-I level was more readily detected in lipoprotein-deficient serum of the MetS group, indicating that the apoA-I exists in a lipid-free state. These results suggest that the MetS group had dysfunctional HDL that enriched TG, apoC-III, CETP, and SAA without antioxidant activity.
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PMID:The functional and compositional properties of lipoproteins are altered in patients with metabolic syndrome with increased cholesteryl ester transfer protein activity. 1995 11

Apolipoprotein A-I (ApoA-I) is the most abundant protein constituent of high-density lipoprotein (HDL). Reduced plasma HDL and ApoA-I levels have been found to be associated with obesity and metabolic syndrome in human beings. However, whether or not ApoA-I has a direct effect on obesity is largely unknown. Here we analysed the anti-obesity effect of ApoA-I using two mouse models, a transgenic mouse with overexpression of ApoA-I and the mice administered with an ApoA-I mimetic peptide D-4F. The mice were induced to develop obesity by feeding with high fat diet. Both ApoA-I overexpression and D-4F treatment could significantly reduce white fat mass and slightly improve insulin sensitivity in the mice. Metabolic analyses revealed that ApoA-I overexpression and D-4F treatment enhanced energy expenditure in the mice. The mRNA level of uncoupling protein (UCP)1 in brown fat tissue was elevated by ApoA-I transgenic mice. ApoA-I and D-4F treatment was able to increase UCP1 mRNA and protein levels as well as to stimulate AMP-activated protein kinase (AMPK) phosphorylation in brown adipocytes in culture. Taken together, our results reveal that ApoA-I has an anti-obesity effect in the mouse and such effect is associated with increases in energy expenditure and UCP1 expression in the brown fat tissue.
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PMID:Apolipoprotein A-I possesses an anti-obesity effect associated with increase of energy expenditure and up-regulation of UCP1 in brown fat. 2019 37

Obesity is associated with increased serum endocannabinoid (EC) levels and decreased high-density lipoprotein cholesterol (HDLc). Apolipoprotein A-I (apo A-I), the primary protein component of HDL is expressed primarily in the liver and small intestine. To determine whether ECs regulate apo A-I gene expression directly, the effect of the obesity-associated ECs anandamide and 2-arachidonylglycerol on apo A-I gene expression was examined in the hepatocyte cell line HepG2 and the intestinal cell line Caco-2. Apo A-I protein secretion was suppressed nearly 50% by anandamide and 2-arachidonoylglycerol in a dose-dependent manner in both cell lines. Anandamide treatment suppressed both apo A-I mRNA and apo A-I gene promoter activity in both cell lines. Studies using apo A-I promoter deletion constructs indicated that repression of apo A-I promoter activity by anandamide requires a previously identified nuclear receptor binding site designated as site A. Furthermore, anandamide-treatment inhibited protein-DNA complex formation with the site A probe. Exogenous over expression of cannabinoid receptor 1 (CBR1) in HepG2 cells suppressed apo A-I promoter activity, while in Caco-2 cells, exogenous expression of both CBR1 and CBR2 could repress apo A-I promoter activity. The suppressive effect of anandamide on apo A-I promoter activity in Hep G2 cells could be inhibited by CBR1 antagonist AM251 but not by AM630, a selective and potent CBR2 inhibitor. These results indicate that ECs directly suppress apo A-I gene expression in both hepatocytes and intestinal cells, contributing to the decrease in serum HDLc in obese individuals.
Obesity (Silver Spring) 2012 Apr
PMID:Inhibition of apolipoprotein A-I gene expression by obesity-associated endocannabinoids. 2201


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