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Query: UMLS:C0028754 (obesity)
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Nowadays besides the commonly accepted atherogenic risk factors a special emphasis is laid on the significance of testosterone in atherogenesis in men which physiologic deficit during "andropause" is able to promote this pathology. An elevated estradiol:testosterone ratio seems to be an independent risk factor of atheromatous heart complications. There is a proved positive correlation between free testosterone, total testosterone, dihydrotestosterone and HDL-cholesterol, apoA1 apolipoprotein. The relationship between LDL-cholesterol, VLDL-cholesterol, total cholesterol and total and free testosterone seems to be unanimous, but in certain studies the beneficial influence of testosterone on the mentioned lipids has been observed. The discussed hormone is also functionally connected with coagulation and fibrynolisis; a positive correlation was found between endogenous testosterone and tPA-Fx and a negative correlation between testosterone and PAI-1, fibrinogen, D-dimers, alpha 2-antiplasmin. Testosterone is a functional regulator of the vascular tonus and influences on reological properties of microcirculation (the application of testosterone infusion into canine coronary arteries causes the dilatation of main and the small vessels, through NO syntetase induction and ATP-dependent K(+)- channel activation). A statistically significant positive correlation between testosterone and insulin has been stated (an elevated oestradiol:testosterone ratio is connected with the insulin resistance). Additionally a negative relationship between testosterone and android obesity has been observed. Although nowadays there are more and more facts proving the benefits of the retaining the proper testosterone levels in aging men, the final influence of the testosterone supplementary therapy on atherogenesis is not solved.
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PMID:[Testosterone and atherosclerosis in males during andropause]. 1039 Oct 62

We investigated in a pilot study the effect of testosterone suppression on lipoprotein metabolism, insulin, and leptin in 10 men who were treated either with cetrorelix, an antagonist of gonadotropin releasing hormone, or with placebo (P). Group C + C (n = 4) was treated with 10 mg cetrorelix as daily subcutaneous injections for five days and with a subsequent injection of 60 mg cetrorelix depot. Group C + P (n = 3) received 10 mg cetrorelix as daily intramuscular injections for five days and a subsequent injection of placebo depot. Group P + P (n = 3) received placebo both as daily and depot injections. Treatment with cetrorelix reversibly suppressed testosterone to castrate levels for three weeks in group C + C and for one week in group C + P. Compared to baseline, treatment with cetrorelix increased serum levels of apolipoprotein (apo) A-I, HDL subclass LpA-I, insulin, and leptin. In the group P + P, treatment with placebo was not associated with any change of these parameters. Compared to baseline and group P + P, treatment with cetrorelix in groups C + C and C + P did not lead to considerable or consistent changes in the plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), lipoprotein lipase, and hepatic lipase (HL). Only the pooled data of groups C + C and C + P unraveled small but statistically significant decreases of HL and CETP activities in response to cetrorelix. In conclusion, the small or absent effects of cetrorelix on LCAT, CETP, PLTP, LPL, and HL indicate that testosterone regulates HDL levels by other metabolic pathways. The increases of insulin and leptin in response to cetrorelix suggest that testosterone influences HDL metabolism also via obesity and insulin resistance. These effects, however, are rather in contrast to the HDL raising effect of suppressed testosterone.
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PMID:Effects of testosterone suppression in young men by the gonadotropin releasing hormone antagonist cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin. 1061 83

The 'metabolic syndrome' is a special clinical entity characterized by upper body segment obesity (android obesity), together with one or more of a constellation of metabolic disorders that includes glucose intolerance, which may amount to frank diabetes mellitus, hypertension, cardiovascular lesions, hyperuricemia, and dyslipidemias (hypercholesterolemia, hypertriglyceridemia and reduced serum HDL). Recently, lipoprotein (Lp) (a) proved to be a new member in this syndrome. Lp(a) has the distinctive feature of containing apolipoprotein (a), which is a glycoprotein linked to apo B100, and has a similarity to plasminogen; it is also structurally related to LDL. Lp(a) is a macromolecular complex which is genetically determined, and has been identified as an independent risk factor for premature coronary artery disease (CAD). It is elevated in diabetic and non-diabetic android obese subjects, and aggravates the atherogenic effect of diabetes mellitus. Lp(a) is poorly influenced either by dietary measures or by hypolipidemic drugs. Unfortunately, few pharmacologic agents, such as niacin, nicotinic acid, sex hormones (estrogen and testosterone), alcohol and neomycin, affect Lp(a).
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PMID:Lipoprotein (a) in android obesity and NIDDM: a new member in 'the metabolic syndrome'. 1066 39

Several epidemiological studies have shown that the prevalence of ischemic heart disease is higher in occupational drivers than in people with other occupations. Although occupation categories can be surrogate measures for coronary risk factors, the relationships between taxi driving and severity of coronary heart disease (CHD) has not been investigated. Even more important, the contribution of risk factors to the severity of CHD in taxi drivers remains unclear. Our study tested the hypothesis that taxi driving could be associated with the severity of CHD. We also examined the relation between this occupation and risk factors and social lifestyle. We analyzed the coronary angiograms of 57 consecutive male taxi driver patients and compared them with those of 215 age-adjusted male non-taxi-driver patients. The number of diseased vessels and risk factors were compared between two groups. The prevalence of myocardial infarction and multi-vessel disease was higher in the taxi-driver patients than in the non-taxi-driver patients. The taxi-driver patients had higher prevalence of body mass index (BMI), diabetes, and smoking, higher levels of low-density lipoprotein cholesterol (LDL-C), and lower levels of apolipoprotein AI (ApoAI). Multiple logistic regression analysis showed that multi-vessel disease was associated with BMI and diabetes mellitus in taxi-driver patients. The taxi-driver patients were characterized by more extensive coronary atherosclerosis associated with higher prevalence of diabetes mellitus and obesity. These characteristics may be explained by in part their working environment.
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PMID:Characteristics of coronary heart disease in Japanese taxi drivers as determined by coronary angiographic analyses. 1068 Mar 6

Data on lipid metabolism in 109 cases of endometrial carcinoma and 33 patients in control are presented. Relevant disorders were detected in 72.5% of the study group [stage I obesity--23 (21.1%); II--29 (26.6%); III--25 (22.9%); IV--2 (1.9%)] which was 1.5 times the mean level in controls (51.5%). The abdominal pattern of obesity was predominant (77.7%). Symptoms of cardiosclerosis were identified in 93 patients with endometrial tumors (85.3%), 93.5% of the latter group presenting with concomitant hyperglyceridemia. In 68.8% of endometrial carcinoma patients, incidence of arterial hypertension was higher than in controls (54.5%). Lipoproteins played a major role in dyslipoproteid pathogenesis involved in obesity and high blood pressure. A study of the insertion-deletion (I/D) polymorphism of apolipoprotein AI genes showed two deletion alleles (DD--6%) and one heterozygote (ID--3%) in control group; no deletion alleles were identified in endometrial tumor patients (0.1 (p(0.05). An investigation of the I/D polymorphism of angiotensin-converting enzyme genes identified deletion homozygotes in 30, insertion homozygotes (II)--27, and heterozygotes--41% (control). In endometrial cancer group, the deletion allele distribution was: DD--29; II--28 and ID--45%. Deletion allele frequency in control was 0.485 while in endometrial carcinoma--0.484 (p(0.05), i.e. with out significant difference.
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PMID:[Parameters of lipid metabolism and polymorphism of apolipoprotein aI and angiotensin-converting enzyme genes in patients with endometrial carcinoma]. 1078 24

The hypertriglyceridemia attends the physiopathology of the atherosclerosis by various mechanisms: association of low levels of high density lipoprotein-cholesterol (HDL-c), modification of quality of low density lipoprotein-cholesterol (LDL-c), influence on hemostatic processes, association with other hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia distinguishes in primary and secondary. In primary forms the origin is essentially genetic, while the secondary ones are metabolic consequence of various pathologies (renal, thyroid, diabetes mellitus etc.). The hypertriglyceridemia's treatment is founded on a correct feeding and/or on eventual use of drugs. Apart from the secondary forms, in which is obligatory to treat at first the basal disease, the pharmacological therapy of the hypertriglyceridemia is suggested only in resistant cases to alone dietetic therapy and overall in presence of other factors of atherothrombotic hazard. The most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases inhibitors is the acarbose. It reduces the biosynthesis of very low density lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic metabolism. Atorvastatin and cerivastatin develop a greater action to reduce serum levels of triglycerides as to the foregoing ones because of the better selectivity of receptor binding, the greater halflife and inhibition of the apolipoprotein's B100 synthesis.
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PMID:[Treatment of hypertriglyceridemia. Current aspects]. 1093 25

Lipoprotein and apolipoprotein changes were evaluated in 10-week-old Zucker diabetic fatty (ZDF) male rats following 12 weeks of insulin treatment, which normalized blood glucose and maintained weight gaining characteristic of nondiabetic Zucker fatty rats. Compared with untreated ZDF rats (saline-injected), insulin treatment resulted in increased very-low-density lipoprotein (VLDL; d < 1.006 g/mL) and decreased alpha lipoprotein on agarose gel electrophoresis. These findings were consistent with an observed increase in VLDL triglyceride and cholesterol, and decreased high-density lipoprotein (HDL) cholesterol with insulin treatment in isolated lipoproteins. B100 levels were unchanged by insulin treatment, but B48 levels were significantly increased in the VLDL fraction. Insulin treatment depressed apolipoprotein (apo) A-I levels in HDL, but had little effect on total apo E, apo A-IV, or apo C, although apo C was redistributed to the VLDL fraction. These results suggest that insulin treatment of ZDF rats normalizes hyperglycemia and prevents age-related changes in lipoprotein parameters associated with development of insulinopenic diabetes. Insulin therapy in ZDF rats thereby sustains the hyperlipidemic lipoprotein pattern associated with hyperinsulinemia and obesity.
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PMID:Insulin-treated Zucker diabetic fatty rats retain the hypertriglyceridemia associated with obesity. 1109 5

The high triglyceride (TG) and low high density lipoprotein (HDL) cholesterol dyslipidemia has been associated with increased postprandial lipemia. Although fasting TG is a powerful predictor of postprandial hyperlipidemia, the role of hypoalphalipoproteinemia in postprandial TG metabolism is uncertain. We have studied postprandial lipemia among 63 men with low fasting plasma HDL cholesterol concentrations (<0.9 mmol/L), but with either low (<2.0 mmol/L) or high (>2.0 mmol/L) fasting plasma TG levels. A significant relationship was noted between postprandial TG response and fasting HDL cholesterol concentration (r = -0.43; P: < 0.0005). We also found that men with high TG/low HDL dyslipidemia (high TG and low HDL cholesterol; n = 16) were characterized by abdominal obesity as well as increased visceral adipose tissue accumulation, whereas normolipidemic controls (low TG and high HDL cholesterol; n = 26) and men with isolated low HDL cholesterol concentrations (low TG and low HDL cholesterol; n = 17) were not characterized by features of the insulin resistance syndrome (visceral obesity, hyperinsulinemia, and hypertriglyceridemia). Although controls and men with isolated low HDL cholesterol levels had similar postprandial lipemic responses, men with the high TG/low HDL dyslipidemia had a marked increase in their postprandial TG responses to the fat load compared with the other subgroups (P: < 0. 001). Men with the high TG/low HDL dyslipidemia were also characterized by higher concentrations of apolipoprotein (apo) B-48 and B-100 particles (chylomicron remnants and very low density lipoproteins, respectively) before and during the postprandial period compared with the other subjects. These results suggest that low HDL cholesterol concentration is a heterogeneous metabolic phenotype that it is not associated with postprandial hyperlipidemia unless accompanied by other features of the insulin resistance syndrome.
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PMID:Metabolic heterogeneity underlying postprandial lipemia among men with low fasting high density lipoprotein cholesterol concentrations. 1113 11

To elucidate to what extent apolipoprotein (apo) E polymorphism modulates obesity-induced dyslipidemias during young adulthood, longitudinal data on 759 individuals (72% white/28% black; initial and follow-up mean age, 25.9 and 32.7 years) were examined. Among both races and the total sample, the apo E2 group (with E2/2 or E2/3 phenotype) had significantly lower and the apo E4 (with E4/4 or E3/4 phenotype) group higher low-density lipoprotein (LDL) cholesterol than the apo E3 (with E3/3 phenotype) group at both examinations. In addition, the apo E2 group displayed higher high-density lipoprotein (HDL) cholesterol in the total sample. No allele-specific effect was noted for the longitudinal changes (Delta). An increase in Delta adiposity, measured as Delta body mass index (BMI), was accompanied by higher increase in Delta LDL cholesterol in the e4 carriers than the e2 carriers among the whites (P <.05) and the total sample (P <.01); an increase in Delta triglycerides and decrease in Delta HDL cholesterol in the e2 carriers than the e4 carriers among all the groups (P <.05 to.001). Among the apo E phenotype groups, the incidence of high (>75th percentile specific for race and sex) LDL cholesterol at follow-up was in the order E4 > E3 > E2 both in the obese (BMI > 30; P for trend =.033) and the nonobese (BMI < 25; P for trend =.035) groups. Although the increase of low (<25th percentile specific for race and sex) HDL cholesterol or high triglycerides showed no apo E phenotype-specific trend, the incidence of high triglycerides without high LDL cholesterol was in the order E2 > E3 > E4 only in the obese group (P for trend =.025). The prevalence trend for dyslipidemias at follow-up among the persistently obese and nonobese groups also gave similar results. Thus, apo E gene locus influences not only the levels of certain lipoprotein variables during young adulthood, but also modulates the association between obesity and dyslipidemias.
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PMID:Apolipoprotein E polymorphism modulates the association between obesity and dyslipidemias during young adulthood: The Bogalusa Heart Study. 1139 47

Excess tissue glucocorticoid action may underlie the dyslipidemia, insulin resistance, and impaired glucose tolerance of the metabolic syndrome. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyzes conversion of circulating inert 11-dehydrocorticosterone into active corticosterone, thus amplifying local intracellular glucocorticoid action, particularly in liver. The importance of 11beta-HSD-1 in glucose homeostasis is suggested by the resistance of 11beta-HSD-1(-/-) mice to hyperglycemia upon stress or obesity, due to attenuated gluconeogenic responses. The present study further investigates the metabolic consequences of 11beta-HSD-1 deficiency, focusing on the lipid and lipoprotein profile. Ad lib fed 11beta-HSD-1(-/-) mice have markedly lower plasma triglyceride levels. This appears to be driven by increased hepatic expression of enzymes of fat catabolism (carnitine palmitoyltransferase-I, acyl-CoA oxidase, and uncoupling protein-2) and their coordinating transcription factor, peroxisome proliferator-activated receptor-alpha (PPARalpha). 11beta-HSD-1(-/-) mice also have increased HDL cholesterol, with elevated liver mRNA and serum levels of apolipoprotein AI. Conversely, liver Aalpha-fibrinogen mRNA levels are decreased. Upon fasting, the normal elevation of peroxisome proliferator-activated receptor-alpha mRNA is lost in 11beta-HSD-1(-/-) mice, consistent with attenuated glucocorticoid induction. Despite this, crucial oxidative responses to fasting are maintained; carnitine palmitoyltransferase-I induction and glucose levels are similar to wild type. Refeeding shows exaggerated induction of genes encoding lipogenic enzymes and a more marked suppression of genes for fat catabolism in 11beta-HSD-1(-/-) mice, implying increased liver insulin sensitivity. Concordant with this, 24-h refed 11beta-HSD-1(-/-) mice have higher triglyceride but lower glucose levels. Further, 11beta-HSD-1(-/-) mice have improved glucose tolerance. These data suggest that 11beta-HSD-1 deficiency produces an improved lipid profile, hepatic insulin sensitization, and a potentially atheroprotective phenotype.
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PMID:Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null mice. 1154 66


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