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

The administration of a single injection of tumor necrosis factor (TNF) produces a variety of acute and sustained biological effects, including hyperlipidemia, stimulation of hepatic lipogenesis, decreases in adipose tissue lipoprotein lipase activity, and anorexia with weight loss. Chronic administration of a fixed dose of TNF produces tachyphylaxis to the anorectic/cachectic effects of TNF. We now report that the hyperlipidemic effect of TNF persists during chronic TNF administration in the absence of any cachectic effect of TNF. Sprague-Dawley rats injected with TNF (250 micrograms/kg) show a significant decrease in weight over the next 24 h which can be accounted for by decreases in food and water intake accompanied by an increase in urine output. With subsequent daily injections of TNF, treated rats begin eating and rapidly regain weight. Hypertriglyceridemia persists for up to 10 days of daily injections of TNF. After three daily injections of TNF, no decreases were seen in lipoprotein lipase activity in a wide variety of tissues. De novo hepatic lipogenesis remained increased in TNF-treated animals after four daily injections, but by the fifth day hepatic lipogenesis returned to normal. After 5 days of TNF treatment the acute incorporation of labeled glycerol into serum triglycerides remained elevated. These data indicate that hyperlipidemia persists during multiple daily injections of TNF and that TNF induced hypertriglyceridemia is not inevitably linked to the syndrome of cachexia.
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PMID:Persistence of the hypertriglyceridemic effect of tumor necrosis factor despite development of tachyphylaxis to its anorectic/cachectic effects in rats. 271 42

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The natural history of nonalcoholic fatty liver: a follow-up study. 748 79

Cytokines induce a number of changes in lipid metabolism that can produce hyperlipidemia. Leukemia inhibitory factor (LIF), a recently discovered cytokine, has been suggested to play a role in the cancer cachexia syndrome through its ability to decrease lipoprotein lipase (LPL) activity. This study explores the mechanism by which LIP decreases LPL activity in cultured adipocytes and determines its effects on fatty acid synthesis and lipolysis to see if it shares the same catabolic effects on fat cells as seen with other cytokines, such as tumor necrosis factor (TNF). LIF decreased LPL activity in cultured adipocytes by 44% compared with an 85% decrease produced by TNF. Although the percent decrease in LPL activity is not as great in LIF-incubated adipocytes as in TNF-incubated adipocytes, the half-maximal doses for both cytokines are similar. LPL messenger RNA levels paralleled LPL activity in the LIF-treated adipocytes, suggesting that the effect of LIF on LPL activity is predominantly mediated through transcriptional regulation. In contrast to TNF, LIF tended to increase the de novo synthesis of fatty acids. Acetyl coenzyme-A carboxylase messenger RNA levels paralleled the changes seen in fatty acid synthesis for both cytokines. LIF caused a small increase in lipolysis, whereas TNF increased lipolysis by greater than 2-fold. These results demonstrate that the catabolic effects of LIF are weaker than those of TNF and are predominantly directed toward decreasing LPL activity, which may contribute to the hyperlipidemia associated with infection, inflammation, and cancer.
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PMID:Leukemia inhibitory factor induces changes in lipid metabolism in cultured adipocytes. 801 46

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

The introduction of HAART has changed the nutritional status of HIV patients. In the pre-protease inhibitor (PI) era, more than 60% of HIV-positive persons presented with protein energy malnutrition (PEM) and vitamin and mineral deficit. This caused progressive physical-metabolic wasting (wasting syndrome/cachexia) and increased susceptibility to opportunistic infections and drug toxicity. PEM was a concurrent cause in 80% of deaths attributed to AIDS. Since 1996, the year in which PIs were introduced, the number of patients dying as a result of AIDS has decreased by two thirds, and cachexia is no longer the AIDS terminal phase in developed countries. But different patterns of nutritional status changes have appeared in association with the use of newer anti-HIV therapies and with longer survival of HIV-infected patients. A new clinical and laboratory syndrome--lipodystrophy syndrome--now affects patients receiving PI-based therapy. This syndrome consists of changes in body shape that are caused by an abnormal redistribution of fat. Fat accumulates in the abdominal area (truncal and visceral obesity), in the axillary pads (bilateral symmetric lipomatosis), and in the dorsocervical pads ("buffalo hump," "bull neck") but decreases in the legs, arms, and nasolabial and cheek pads (peripheral lipodystrophy). Hyperlipidemia and insulin resistance are also frequently present (metabolic syndrome X). Pathogenic mechanisms of lipid and fat tissue disturbances are discussed in this article, and the clinical approach to patient management and therapeutic options for lipodystrophy and lipid dysmetabolism is evaluated.
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PMID:Reversal of cachexia in patients treated with potent antiretroviral therapy. 1088 68

We developed a surgical technique for preparing the inguinal fat pad of rats for perfusion that preserves continuous blood flow to the tissue. Fatty acid uptake from the fat pads of fed rats (46.1 +/- 2.1% of arterial supply, n = 82) and release from those of fasted (48 h) animals (51.3 +/- 3.1% of supply, n = 69) occurred principally via the free fatty acid component of the blood; levels of triglycerides, cholestryl esters, and phospholipids did not change significantly. Venous blood flow in perfusions using blood from fed rats was 83.3 +/- 1.7 mL/min and 83.1 +/- 1.5 microL/min in experiments involving fasted donors. Values for arterial (A) and venous (V) pH (A, 7.41 +/- 0.03; V, 7.32 +/- 0.04), pO2 (A, 151.6 +/- 15.7 mm Hg; V, 34.7 +/- 9.2 mm Hg), pCO2 (A, 30.8 +/- 6.6 mm Hg; V, 58.2 +/- 5.2 mm Hg), and hematocrit (A, 44.6 +/- 1.2%; V, 45.7 +/- 1.2%) were unchanged throughout the course of the perfusions. Fat pad and blood perfusates were maintained at 37 degrees C. Tissue homogenates revealed that the total fatty acid content of fat pads from fed rats (333.5 +/- 0.3 mg/g tissue) differed significantly from that in fasted animals (260.7 +/- 0.7 mg/g tissue; P < 0.001). Our technique likely will have many uses in the study of lipid transport and metabolism, hyperlipidemia, and cancer-associated cachexia.
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PMID:Preparation of the inguinal fat pad for perfusion in situ in the rat: a surgical technique that preserves continuous blood flow. 1104 Aug 72

Nutritional alterations are common in HIV infection. Early studies documented weight loss and protein depletion, a finding associated with body cell mass depletion in untreated patients. The application of highly active antiretroviral therapy has led to a decreased incidence of malnutrition, although altered body fat distribution and metabolic alterations, including hyperlipidemia and insulin resistance, are common sequelae. The development of malnutrition is multifactorial and occurs through changes in caloric intake, nutrient absorption, or energy expenditure. Clinically, malnutrition develops as a result of either starvation or cachexia. Other hormonal and endocrinologic alterations include hypercortisolemia and hypogonadism. The rationale for providing nutritional support to AIDS patients is based upon the assumptions that nutrition status can be improved and that such improvements have clinical benefits. The results of hypercaloric feeding studies, including the use of appetite stimulants, indicate that weight gain is possible but that the weight gained is predominantly fat. In contrast, anabolic agents and resistance training exercise have been shown to promote body cell mass repletion and skeletal muscle gain. Cytokine inhibitors also have been evaluated for the treatment of wasting in HIV infection. Development of combination therapies, preventive therapies, and efficient and cost-effective therapies are current tasks in the field.
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PMID:Nutritional alterations associated with HIV infection. 1112 32

Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of caloric restriction were obscured by the varied diet composition of the participants. The Dahl salt-sensitive rat which develops gradual, hypertension-associated diastolic dysfunction was used in this study to assess the impact of caloric restriction upon decompensated pressure-overload hypertrophy. Male Dahl salt-sensitive rats were provided either a low-salt diet or a high-salt diet to initiate heart failure progression. A further subset of high-salt rats underwent 15% calorie restriction, with salt load held constant. Parameters measured included serial systolic blood pressure, body weight, and changes of left ventricular systolic and diastolic parameters and ventricular geometry by echocardiography. After 18 weeks, fasting glucose, blood lipids, heart weight, kidney weight, lung weight, plasma interleukin-6 and TNF-alpha, and cardiac lipid peroxidation were measured. Low-salt rats did not develop heart failure. While high-salt rats displayed features of decompensated pressure-overload hypertrophy, moderate calorie restriction remarkably reduced morbidity. Compared to the high-salt fed group, the high-salt, calorie-restricted group showed reduced blood pressure, delayed onset of cachexia, lower fasting hyperlipidemia, lower cardiac, renal and lung weight, less plasma IL-6 and TNF-alpha, less cardiac oxidative damage, and improved diastolic chamber function and cardiac index. Modest calorie restriction, independent of salt intake, reduced pathogenesis in this well described model of decompensated pressure-overload hypertrophy.
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PMID:Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. 1693 90

The body's resistance to the actions of insulin (type II diabetes defect) results in compensatory increased production and secretion by the pancreas and leads to hyperinsulinemia in order to maintain euglycemia. When insulin secretion cannot be increased adequately (type I diabetes defect) to overcome insulin resistance in maintaining glucose homeostasis, hyperglycemia and glucose intolerance ensues. Insulin resistance and glucose intolerance has been well recognized in patients with advanced chronic kidney diseases (CKD). The etiology may involve uremic toxins from protein catabolism, vitamin D deficiency, metabolic acidosis, anemia, poor physical fitness, inflammation, and cachexia. Glucose and insulin abnormalities in nondiabetic CKD patients are implicated in the pathogenesis of hyperlipidemia and may represent important risk factors for accelerated atherosclerosis in these patients. Insulin secretion inadequacy has been associated with growth retardation in adolescents with CKD. Normal adolescents demonstrate an increase in insulin secretion as they go into puberty. It seems that the puberty growth spurt in adolescents both with normal health and renal failure may require increased insulin secretion as one of its hormonal requirements. Finally, insulin resistance has been associated with CKD. Whether insulin resistance is an antecedent of CKD or a consequence of impaired kidney function has been a subject of debate. The goal of this review was to provide an update of the literature on insulin pathophysiology in CKD, current understanding of its mechanisms, and epidemiological association of insulin resistance and CKD.
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PMID:Insulin and its role in chronic kidney disease. 1792 61

Traditional cardiovascular disease risk factors including hyperlipidemia and obesity are paradoxically associated with improved survival in individuals with advanced chronic kidney disease. Such paradoxes underscore the important role of malnutrition-inflammation-cachexia syndrome in chronic kidney disease mortality and highlight the urgent need for comprehensive but practical nutritional assessment tools. In this Practice Point commentary, Rambod and colleagues discuss a recent paper by Yamada et al. that used the Malnutrition-Inflammation Score (MIS) as the 'reference standard' to validate five simplified nutritional screening tools in 422 Japanese patients on hemodialysis. The study found the Geriatric Nutritional Risk Index to be the most accurate of the simplified tools for identifying those patients on dialysis who are at nutritional risk. The commentary authors discuss Yamada et al.'s study and conclude that although the MIS has been widely used in patients undergoing maintenance dialysis, its wide utility does not automatically make it the ultimate reference standard for assessing other nutritional scoring tools.
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PMID:Malnutrition-Inflammation Score for risk stratification of patients with CKD: is it the promised gold standard? 1817 43


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