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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether the estrogen-induced hyperlipidemia is affected by fasting, male growing chicks were administered subcutaneously a single dose of 17 beta-estradiol (25 mg/kg body wt), and the hormone treatment lasted for 2 days with or without feed (Experiment 1). In the second experiment, chicks were initially fasted for 1 or 3 days, and then treated with the same dosage of 17 beta-estradiol as in Experiment 1 for 2 days without feed. Plasma and liver lipids, and the activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, and hormone-sensitive lipase in the adipose tissue were determined. Compared with fed control chicks, estrogen treatment in fed birds resulted in a marked elevation of plasma lipids, especially triglyceride during the 2-day period (137 vs 2263 mg/dl). In fasted chicks, the present finding that estrogen also induced a marked hyperlipidemia is noteworthy. Upon estrogen treatment (Experiment 1), the level of plasma triglyceride in fasted birds increased about 16 times over that of the fasted control group (133 vs 2093 mg/dl). Even in chicks fasted for 5 days (Experiment 2), estrogen treatment resulted in a persistent hypertriglyceridemia (75 vs 1369 mg/dl). In fed chicks, estrogen treatment also induced a fatty liver with massive accumulation of triglyceride, but the liver of estrogen-treated/fasted chicks appeared to be normal. In both fed and fasted chicks, malic enzyme was found to be the major NADPH producing enzyme in the liver. Upon fasting, both malic enzyme and glucose-6-phosphate dehydrogenase activities decreased significantly (P less than 0.05). In fed chicks, the total activities of both enzymes increased with estrogen treatment, whereas the effect of hormone on these enzymes was less obvious in fasted chicks. The hormone-sensitive lipase activity in the adipose tissue was much lower in fed chicks compared with that of fasted birds (0.15 vs 0.33 nmol of oleic acid released/min/mg protein). Estrogen treatment in fed chicks had no effect on the hormone-sensitive lipase activity, but its activity was enhanced by the hormone treatment in fasted chicks. The present finding that hyperlipidemia persisted in estrogenized chicks during the fasting seems to indicate the complex nature of this hormonal influence on lipid metabolism.
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PMID:Estrogen induces hyperlipidemia in fasted chicks. 230 May 91

The effect of dietary ethanol on metabolic fates of glucose and ethanol, and activities of lipoprotein lipase and hormone-sensitive lipase in several tissues of miniature pigs were determined in vitro. Ethanol and glucose were used at similar rates for fatty acid synthesis in liver and brain and CO2 production in liver. Ethanol was preferred over glucose for fatty acid and CO2 production in ileal mucosal cells. Glucose was the preferred substrate for lipogenesis and oxidation to CO2 in adipose tissue and skeletal muscle, and for oxidation to CO2 in brain. Dietary ethanol decreased glucose and ethanol conversion to fatty acids in ileal mucosa and brain, respectively. Dietary ethanol had no effect on the capacity of liver, adipose tissue, and skeletal muscle to convert either glucose or ethanol to long-chain fatty acids. The capacity to oxidize ethanol, but not glucose, to CO2 in liver was increased by dietary ethanol. No dietary ethanol effect was observed in other tissues. The capacity for removal of plasma triglycerides (based on lipoprotein lipase activity) tended to increase in adipose tissue and skeletal muscle of pigs fed ethanol. Mobilization of long-chain fatty acids from adipose tissue (based on hormone-sensitive lipase activity), triglyceride concentration in plasma, and percentage of lipid in liver remained unchanged when ethanol was fed. Livers of ethanol-fed pigs, however, were larger than livers of control pigs. Our results indicate that feeding miniature pigs 21-37% of total caloric intake as ethanol causes significant metabolic adaptations of lipid metabolism in liver and ileal mucosa, but not in adipose tissue, skeletal muscle, and brain. The ethanol feeding, however, did not cause fatty livers or hyperlipidemia.
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PMID:Adaptation of lipogenesis and lipolysis to dietary ethanol. 311 29

The pathophysiology of familial combined hyperlipidemia (FCHL) is unknown, but altered lipid turnover in peripheral tissues as well as hepatic overproduction of apolipoprotein B have been suggested as possible causes. In the present study, we explored whether a change in triglyceride breakdown by lipolysis in fat cells is present in FCHL. Lipolysis activation by catecholamines was examined in isolated subcutaneous adipocytes from 10 patients with FCHL and 22 healthy control subjects. Lipolysis rate was linear for at least 3 h in both groups. However, a marked (approximately 65%) decrease in the lipolytic response to noradrenaline was found in FCHL. This was also true when lipolysis was maximally stimulated at the receptor level with isoprenaline (nonselective beta-adrenergic agonist), at the adenylyl cyclase level with forskolin, or at the level of the protein kinase hormone-sensitive lipase complex with dibutyryl cAMP. The maximum enzymatic activity of hormone-sensitive lipase was decreased by approximately 40% in FCHL. On the other hand, the lipolytic sensitivity of alpha 2-, beta 1-, and beta 2-adrenoceptors was normal in this condition, as was the number and affinity of beta 1- and beta 2-adrenoceptors. Variations in the maximum lipolysis rate correlated significantly with the variations in hormone-sensitive lipase activity in the whole material, and with the serum values for triglycerides, HDL cholesterol and apoB lipoprotein within the control group, but the serum triglyceride values in FCHL were higher than this correlation predicted. In conclusion, the data demonstrate a marked resistance to the lipolytic effect of catecholamines in fat cells from patients with FCHL, in spite of normal adrenoceptor function. The lipolytic defect appears predominantly to be due to a defect in hormone-sensitive lipase, and may be of importance in the pathophysiology of FCHL.
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PMID:Impaired activation of adipocyte lipolysis in familial combined hyperlipidemia. 773 84

Numerous investigations have demonstrated altered systemic lipid metabolism in cancer patients, as well as aberrant lipid utilization by tumor cells. The most common measure of altered systemic lipid metabolism in these individuals has been hyperlipidemia. Although cachexia is not generally considered to be associated with gynecologic cancers, this study demonstrates the presence of lipolysis-promoting activity, detectable in sera and ascites of ovarian cancer patients and indices of altered systemic lipid metabolism. Elevated lipolysis promoting activity was detectable in the sera of 7/9 patients and in the ascites of 5/5 patients. Since previous studies have indicated that cancer patients exhibit a 2.5-fold enhancement in hormone-sensitive lipase (HSL) versus normal controls, as a potential mechanism for elevated lipolysis, the ability of ascites-derived factors to induce HSl was examined. The addition of three of four ascites fluids increased the level of HSL in normal adipocytes. All of the patients' samples exhibited elevated lipid levels versus normal peritoneal fluid. Isolation and analysis of lipids from three ovarian cancer patients revealed four consistent altered lipid parameters compared to normal peritoneal fluid: elevated monoglycerides, diglycerides, and free fatty acids and decreased triacylglycerides. While "classical" cachexia is not a common feature of ovarian cancer, the presence of circulating lipolysis-promoting activity and altered lipid metabolism, generally observed in cachectic individuals, can be demonstrated in these ovarian cancer patients. Based on recent evidence indicating a role of lipids in carcinogenic initiation or promotion, the presence of tumor-derived lipolysis-promoting factor and lipid metabolism alterations may provide a mechanism for the epidemiologically observed association between lipids and certain cancers, including ovarian cancer.
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PMID:Aberrations in normal systemic lipid metabolism in ovarian cancer patients. 855 25

Cardiovascular complications of obesity are more common in men than women. Sex differences in visceral fat lipolysis may be of importance in this respect, since increased release of free fatty acids (FFAs) from visceral fat to the liver by the portal venous system has been thought to cause several metabolic complications due to obesity, such as hypertension, hyperlipidemia, and glucose intolerance. The aim of this study was to investigate sex differences in clinical characteristics and visceral fat mobilization in obesity. Obese subjects (22 male and 23 female) undergoing elective surgery were matched for body mass index and age. The males had both higher waist-to-hip ratio (WHR), sagittal diameter, blood pressure, fat-cell volume, plasma insulin, glucose, and triglyceride and lower HDL cholesterol levels than the females. The rate of norepinephrine-induced FFA and glycerol release was twofold higher in men (P = .02). No significant reutilization of FFA was observed. The difference in maximum norepinephrine-induced rate of lipolysis between men and women was independent of both WHR and sagittal diameter and was an independent regressor for levels of plasma glucose and plasma HDL cholesterol. Fat-cell volume was an independent regressor for plasma triglycerides and blood pressure. No sex differences in the lipolytic sensitivity to beta 1- or beta 2-adrenoceptor-specific agonists or in the antilipolytic effect of insulin were observed. However, the lipolytic beta 3-adrenoceptor sensitivity was 12 times higher (P = .004) and the antilipolytic alpha 2-adrenoceptor sensitivity 17 times lower (P = .003) in men. Furthermore, lipolysis induced by agents acting at the adenylate cyclase and protein kinase A levels were almost twofold enhanced in men. However, no sex difference in maximum hormone-sensitive lipase activity was observed. In conclusion, in obesity, catecholamine-induced rate of FFA mobilization from visceral fat to the portal venous system is higher in men than women. This phenomenon is partly due to a larger fat-cell volume but also to a decrease in the function of alpha 2-adrenoceptors, an increase in the function of beta 3-adrenoceptors, and an increased ability of cyclic AMP to activate hormone-sensitive lipase. These factors may contribute to gender-specific differences in metabolic and cardiovascular disturbances accompanied by obesity.
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PMID:Sex differences in visceral fat lipolysis and metabolic complications of obesity. 926 Dec 82

The metabolism of free fatty acids (FFA) is altered in two common atherosclerosis-promoting disorders: familial combined hyperlipidemia (FCHL) and insulin resistance syndrome (IRS). It has been suggested that these two conditions may have a common etiology. The enzymes lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) are rate-limiting steps for the turnover of fatty acids in adipose tissue, because they hydrolyze extracellular triglycerides in lipoproteins (LPL) and intracellular triglycerides in adipocytes (HSL). The present study was undertaken to simultaneously determine the activities of LPL and HSL in subcutaneous adipose tissue from male patients with FCHL and IRS. LPL and HSL activity was investigated in 10 nonobese FCHL patients and compared with 10 matched healthy nonobese subjects, and in 8 essentially normolipidemic IRS patients (who did not have overt diabetes mellitus) and compared with 9 nonobese matched control subjects. LPL activity was 43% lower in patients with IRS (P < .0005), as compared with control subjects, but HSL activity was not significantly different in the two groups, On the other hand, HSL activity was decreased by 45% in FCHL patients (P < .01), as compared with control subjects, but LPL activity was not significantly different in FCHL patients and the control group. In conclusion, triglyceride metabolism in adipose tissue is altered in both FCHL and IRS. However, the abnormalities observed involve impaired function of LPL in IRS and impaired function of HSL in FCHL, suggesting separate etiologies for the altered lipolysis in these conditions, at least in male subjects.
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PMID:Adipose tissue lipoprotein lipase and hormone-sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome. 935 2

Overproduction of very low density lipoprotein (VLDL) is the major characteristic of subjects with familial combined hyperlipidemia (FCHL). As enhanced free fatty acid (FFA) flux to the liver may be one of the determinants of VLDL overproduction, we studied FFA changes and products of hepatic FFA metabolism in response to a 24-h oral fat loading test (50 g/m(2)) in 7 FCHL subjects and 7 matched control subjects. The response to the meal was subdivided into a postprandial (up to 8 h after ingestion of the meal) and postabsorptive period (from 8 to 24 h). Although postheparin plasma lipolytic activities were not different between both groups, the postprandial FFA area under the curve (FFA-AUC) and FFA incremental area under the curve (FFA-dAUC) were higher in FCHL subjects than in control subjects (6.05 +/- 0.45 vs. 3.43 +/- 0.46 and 2.60 +/- 0.49 vs. 0.96 +/- 0.31 mmol. h/L, respectively; P < 0.01 for each). The postprandial increase in ketone bodies was almost four times higher in FCHL patients. As ketogenesis occurs predominantly in hepatocytes, these findings suggest that during the postprandial period in FCHL an increased flux of FFA to the liver occurs, possibly because of inadequate incorporation of FFA into triglycerides (TGs) in adipocytes. In the postabsorptive period, FFA and ketone bodies significantly decreased in FCHL subjects, in contrast to control subjects, in whom both increased. These results may represent a diminished release of FFA from adipocytes by hormone-sensitive lipase (HSL) in FCHL patients. The decrease in postabsorptive FFA and ketone bodies in FCHL patients could not be explained by insulin-mediated inhibition of HSL, as both FCHL subjects and control subjects had similar postabsorptive insulin concentrations, which were below fasting concentrations. This study provides in vivo evidence of impaired metabolism of postprandial FFA in FCHL, which may explain in part the hepatic VLDL overproduction characteristic of FCHL subjects.
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PMID:In vivo evidence of defective postprandial and postabsorptive free fatty acid metabolism in familial combined hyperlipidemia. 1088 91

We investigated the mechanisms that lead to combined hyperlipidemia in transgenic mice that overexpress human apolipoprotein (apo) A-II (line 11.1). The 11.1 transgenic mice develop pronounced hypertriglyceridemia, and a moderate increase in free fatty acid (FFA) and plasma cholesterol, especially when fed a high-fat/high-cholesterol diet. Post-heparin plasma lipoprotein lipase and hepatic lipase activities (using artificial or natural autologous substrates), the decay of plasma triglycerides with fasting, and the fractional catabolic rate of the radiolabeled VLDL-triglyceride (both fasting and postprandial) were similar in 11. 1 transgenic mice and in control mice. In contrast, a 2.5-fold increase in hepatic VLDL-triglyceride production was observed in 11. 1 transgenic mice in a period of 2 h in which blood lipolysis was inhibited. This increased synthesis of hepatic VLDL-triglyceride used preformed FFA rather than FFA of de novo hepatic synthesis. The 11.1 transgenic mice also presented reduced epididymal/parametrial white adipose tissue weight (1.5-fold), increased rate of epididymal/parametrial hormone-sensitive lipase-mediated lipolysis (1.2-fold) and an increase in cholesterol and, especially, in triglyceride liver content, suggesting an enhanced mobilization of fat as the source of preformed FFA reaching the liver. Increased plasma FFA was reverted by insulin, demonstrating that 11.1 transgenic mice are not insulin resistant. We conclude that the overexpression of human apoA-II in transgenic mice induces combined hyperlipidemia through an increase in VLDL production. These mice will be useful in the study of molecular mechanisms that regulate the overproduction of VLDL, a situation of major pathophysiological interest since it is the basic mechanism underlying familial combined hyperlipidemia.
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PMID:Increased production of very-low-density lipoproteins in transgenic mice overexpressing human apolipoprotein A-II and fed with a high-fat diet. 1108 33

One of the best studied aspects of the insulin resistance syndrome in familial combined hyperlipidemia (FCHL) is impaired insulin-mediated suppression of FFA by diminished inhibition of hormone-sensitive lipase (HSL). In vitro experiments have shown that stimulation of HSL activity by catecholamines is decreased in FCHL. The aim of this study was to investigate HSL inhibition by insulin and stimulation by endogenous catecholamines in vivo in FCHL patients. Twelve FCHL subjects using lipid-lowering medication and 12 controls underwent a mental stress test after random ingestion of either 50 g glucose or placebo. After ingestion of glucose, insulin concentrations increased from 76.8 +/- 21.5 pM to a maximum of 520.2 +/- 118.4 pM (P < 0.01) in FCHL and from 38.0 +/- 5.0 to 221.7 +/- 25.1 pM (P < 0.01) in controls. The percent decreases in plasma FFA during the first hour after glucose ingestion were similar in FCHL and controls (67 +/- 5% vs. 72 +/- 3%, respectively), suggesting a comparable inhibition of HSL in both. During the placebo test, FFA increased similarly in FCHL (56 +/- 9%) and controls (57 +/- 19%). In contrast, FFA concentrations did not change during mental stress after ingestion of glucose (from 0.17 +/- 0.02 to 0.15 +/- 0.02 mmol/liter in FCHL and from 0.11 +/- 0.02 to 0.12 +/- 0.02 mmol/liter in controls). In conclusion, the present study provides in vivo evidence for intact insulin-mediated suppression of FFA in FCHL, although this inhibition of HSL was achieved by higher insulin levels, suggesting insulin resistance at the level of HSL. Secondly, the induction of HSL activity by endogenous catecholamines in vivo is not decreased in FCHL, in contrast to earlier in vitro findings. Finally, catecholamine-induced HSL activation can be inhibited by insulin in a similar manner in both FCHL and controls.
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PMID:In vivo modulation of plasma free fatty acids in patients with familial combined hyperlipidemia using lipid-lowering medication. 1193 85

This study aimed to assess the role of complement C3, hormone-sensitive lipase (HSL), and peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression in familial combined hyperlipidemia (FCHL). mRNA expression of these 3 determinants of adipose tissue fatty acid (FA) metabolism was quantified in subcutaneous adipose tissue of 41 Finnish FCHL patients and 14 normolipidemic control subjects. No difference in steady-state mRNA expression level of C3, HSL, or PPARgamma mRNA was detected between the FCHL patients and the control subjects. Adipose tissue C3 mRNA expression level correlated with the area under the curve (AUC) for glucose and for insulin in FCHL patients and control subjects. HSL mRNA level was positively correlated with waist-to-hip ratio in patients, whereas the correlation was negative in control subjects. A significant correlation was observed for PPARgamma with free FA (FFA)-AUC in the FCHL group, and an inverse correlation with serum triglycerides (TG) in the control subjects. Although no difference in adipose tissue gene expression of C3, HSL, or PPARgamma was observed between the FCHL patients and the control subjects, several significant correlations were observed between the mRNA levels and FCHL-related metabolic parameters. Thus, the genes of C3, HSL, and PPARgamma may exert a modifying effect on lipid and glucose metabolism in FCHL. However, defects in adipose tissue expression of these genes are not likely to play a primarily role in the pathogenesis of FCHL in Finnish FCHL families.
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PMID:C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor gamma expression in adipose tissue of familial combined hyperlipidemia patients. 1197 3


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