Fat Overload Research Articles

Similar increase in oxidative stress after fat overload in persons with baseline hypertriglyceridemia with or without the metabolic syndrome

Objective We compared the levels of biomarkers of oxidative stress before and after a fat overload in three groups. Materials and methods 17 controls and two groups with hypertriglyceridemia: 43 without the metabolic syndrome (TG-non-MS) and 29 with the metabolic syndrome (TG-MS). All subjects underwent a 60 g fat overload. Baseline measurements included glucose, BMI (body mass index), waist circumference and HOMA IR (homeostasis model assessment insulin resistance). Cholesterol, triglycerides, HDL (high density lipoprotein) cholesterol, TNF-alpha (tumor necrosis factor) and IL-6 (interleukin-6), lipoperoxide (LPO), carbonylated proteins, reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GSH-PX), glutathione reductase (GSH-Rd), catalase and glutathione transferase (GST) were measured at baseline and 3 h after fat overload. Results Compared to the controls, the two patient groups had higher plasma levels at baseline and after overload of cholesterol, triglycerides and apolipoprotein B, LPO, carbonylated proteins and GSSG, and lower levels of antioxidants at baseline and after the fat overload. Conclusion The two patient groups had the same degree of oxidative stress.

Visceral obesity and the heart

Obesity and particularly its deleterious form, visceral adiposity, has reached a high prevalence in the industrialized world owing to the lack of exercise and the widely available energy-dense diet. As a consequence, cardiovascular diseases and metabolic disorders are afflicting an unprecedented number of individuals at a world-wide scale. Over the last decades, investigations have established firm links between visceral obesity and the development of cardiovascular diseases. Moreover, studies in the field of lipid partitioning have demonstrated that inadequacy of homeostatic mechanism ensuring adequate handling of energy surplus is associated with accumulation of visceral fat and lipid overload of internal organs, which are participating to the development of heart diseases. Visceral obesity and its metabolic consequences often referred to as the metabolic syndrome is associated with the production of an atherosclerosis prone milieu. In this review, clinical implications of visceral obesity on the development of cardiovascular disorders are reviewed along with important mechanisms participating to the development of these disorders. Implications and failure of lipid partitioning and some of the potential pathways mediating development of heart diseases are also covered in view of recent development of therapeutic options.

An Apolipoprotein A-II Polymorphism (-265T/C, rs5082) Regulates Postprandial Response to a Saturated Fat Overload in Healthy Men ,

Apolipoprotein (Apo) A-II is an apolipoprotein with an unknown role in lipid metabolism. It has been suggested that the presence of the less frequent allele of a single nucleotide polymorphism (Apo A-II -265T/C, rs5082) reduces the transcription rate of Apo A-II and enhances VLDL postprandial clearance in middle-aged men. To further investigate the role of Apo A-II -265T/C on lipid metabolism, we studied 88 normolipidemic young men. The participants were given a fatty meal containing 1 g fat and 7 mg cholesterol/kg weight and capsules containing 60,000 IU vitamin A (retinyl palmitate, 15.15 mg RE) per square meter body surface area. Postprandial lipemia was assessed during the 11 h following the meal. Total cholesterol (Chol) and triacylglycerols (TG) in plasma and TG-rich lipoproteins (TRL) (large TRL and small TRL) were measured, as well as HDL, Apo A-I, Apo B, Apo B-48, and Apo B-100. Postprandial responses were higher in the TT group than in carriers of the minor allele (CC/TC) for total TG in plasma (21.37% of change of area under curve, P = 0.014), large TRL-TG (24.75% change, P = 0.017) and small TRL-Chol (26.63% change, P = 0.003). Our work shows that carriers of the minor allele for Apo A-II -265T/C (CC/TC) have a lower postprandial response compared with TT homozygotes. This finding may partially explain the role of Apo A-II in lipid metabolism and can identify a population with a decreased risk of cardiovascular disease, as corresponds to the lower level of postprandial hypertriglyceridemia.

Apoptosis in the liver: a matter of ion fluxes and oxidative stress: Third International Conference of the Collaborative Research Center ‘Experimental Hepatology’ (SFB‐575), Düsseldorf, Germany, 13–14 October 2006

The cell death of hepatocytes is a characteristic feature of liver damage triggered by viral infection, drug abuse, fat overload or autoimmunity. Apoptosis is currently the best-understood form of cell death; however, the precise mechanisms leading to apoptosis in liver disease are largely unknown. Several cellular processes including alterations in cell hydration and ion homeostasis, osmotic and oxidative stress, lysosomal permeabilization as well as alternate forms of cell death may contribute to liver damage. The intriguing complexity and relevance of these processes for liver failure were addressed at the Third International Conference of the Collaborative Research Center 'Experimental Hepatology' (SFB-575),which was held in Düsseldorf, Germany, in 13-14 October 2006. The aim of this symposium was to bring together leading researchers studying cell death pathways in the liver and other systems and to share ideas and recent research findings. This report covers some of the salient and stimulating contributions of the meeting and gives an updated survey of the advances in this burgeoning field of translational medicine.

Pro12Ala Sequence Variant of the PPARG Gene Is Associated with Postprandial Hypertriglyceridemia in Non-E3/E3 Patients with the Metabolic Syndrome

Postprandial hypertriglyceridemia, a component of the metabolic syndrome, has varied etiology and involves many genes related to triglyceride metabolism. Variations in these genes may affect postprandial hypertriglyceridemia in the context of the metabolic syndrome. We orally administered 60 g of fat overload to 74 patients with the metabolic syndrome. We then measured baseline concentrations of cholesterol, triglycerides, HDL cholesterol, apolipoprotein AI, apolipoprotein B, uric acid, and uric acid excretion; we also performed homeostasis model assessments of insulin resistance and insulin sensitivity. At 3 h, we measured triglycerides, cholesterol, apolipoprotein AI, and apolipoprotein B. Patients were considered to have postprandial hypertriglyceridemia if the difference in plasma triglycerides between baseline and 3 h after the test was 1.71 mmol/L or more. We also measured anthropometrical variables and classified the patients according to their peroxisome proliferative activated receptor, gamma (PPARG) gene and apolipoprotein E (APOE) genotype. Postprandial hypertriglyceridemia occurred in 64.7% of patients with the Ala12 allele vs 19.9% of the Pro12Pro patients, (P = 0.00032; odds ratio, 7.6), and in 87.5% of the patients with both the Ala12 allele and the non-E3/E3 APOE genotype (odds ratio, 23.8). Logistic regression analysis showed that PPARG and APOE sequence variants were associated with the presence of postprandial hypertriglyceridemia. The Pro12Ala PPARG sequence variant together with a non-E3/E3 APOE genotype is associated with a high risk for postprandial hypertriglyceridemia in patients with the metabolic syndrome, indicating a close association between these genes and the regulation of lipoproteinase clearance.

Combined effects of high-fat feeding and circadian desynchronization

To assess whether circadian desynchronization leads to metabolic alterations capable of promoting dietary obesity and/or impairing glucose tolerance. Rats fed either with chow pellets (i.e., low-fat diet with 4% mass of fat) or high-fat diet (34% mass of fat). Half of each diet group was exposed to a fixed light-dark cycle or to a 10-h weekly shift in the light-dark cycle from Thursday to Sunday (20 shifts). To enforce the shifted animals to be active at unusual times of the day, food was available only during the daily dark period for all groups. Shifting the light-dark cycle on a weekly basis was efficient to induce circadian desynchronization, as evidenced by strong disturbances in the daily expression of locomotor activity. Shifted rats fed with a nocturnal low-fat diet had lower plasma insulin and similar blood glucose compared to rats fed with the same diet under a fixed light-dark cycle. Nocturnal high-fat feeding led to an abdominal fat overload associated with increased plasma leptin and basal glucose. These metabolic changes were not significantly modified by circadian desynchronization. Chronic desynchronization with low-fat diet impaired insulin regulation. Metabolic changes induced by the high-fat diet were not aggravated by chronic desynchronization.

The Apolipoprotein E Genotype Predicts Postprandial Hypertriglyceridemia in Patients with the Metabolic Syndrome

Apolipoprotein E (apo E) is a constituent molecule of the triglyceride-rich lipoproteins and participates in their clearance. Polymorphisms in the apo E gene are associated with increased fasting and postprandial levels of triglycerides. We studied 66 patients with the metabolic syndrome, none of whom had diabetes. Details were recorded for cholesterol, triglycerides, apo AI, apo B, insulin, homeostasis model assessment of insulin resistance, homeostasis model assessment of insulin secretion, uric acid, 24-h uric acid urinary excretion, high-density lipoprotein cholesterol, waist to hip ratio, body mass index, and age. The patients were given a 60-g fat overload (Supracal), and measurements were made at 4 h of cholesterol, triglycerides, high-density lipoprotein cholesterol, apo AI, and apo B. Patients who did not have the E3/3 genotype had an odds ratio of postprandial hypertriglyceridemia of 6.2 (confidence interval, 1.41-16.08; P = 0.01) and an odds ratio of hyperuricemia compared with the E3/3-positive patients of 7.5 (confidence interval, 1.04-39.31; P = 0.02). This study shows that patients with the metabolic syndrome who do not have the E3/3 genotype have a greater risk of hyperuricemia and postprandial hypertriglyceridemia after a fat overload.

Hemophagocytic syndrome after Kawasaki disease.

Hemophagocytic syndrome (HPS) is a rare and life-threatening disease in which a generalized histiocytic proliferation results in hemophagocytosis and up-regulation of inflammatory cytokines. This syndrome has been associated with infections, malignancy, drugs and immunologic triggers such as Kawasaki disease (KD). We describe the clinical and laboratory features of two children with HPS after KD and review the three previously reported pediatric cases of recrudescence of HD leading to HPS.

Pancreatic toxicity after liposomal amphotericin B.

Though liposomal amphotericin B has been available in Germany since 1992, efficacy and safety of this formulation of amphotericin B are still not well-documented in children. As far as gastrointestinal side-effects are concerned, an elevated alkaline phosphatase and elevated transaminases have been reported. In our department, liposomal amphotericin B had been used since 1994 to treat patients with proven or suspected fungal infections in a daily dose of 1-3 mg kg-1. Additionally, patients with high-dose chemotherapy and autologous stem cell support received liposomal amphotericin B prophylactically in a dose of 1 mg kg(-1) three times per week. We performed a retrospective analysis of all 31 patients who had received liposomal amphotericin B by 1999. In five patients, an isolated transient elevation of the serum lipase level during, or shortly after, the therapy with liposomal amphotericin B was detected. Three of these patients showed clinical signs of pancreatitis, with one patient displaying slightly elevated transaminases. So far, elevated levels of serum lipase have not been described as a possible side-effect of a liposomal amphotericin B therapy. The pathogenesis of this elevation is unclear. As possible reasons, an enzyme induction due to fat overload or a toxic damage of the pancreatic tissue by the liposomes or amphotericin B itself are discussed.

The age-related differences in obese and fatty acid synthase gene expression in white adipose tissue of rat

To determine if the age-dependent increase of adiposity is directly related to altered obese ( ob) and fatty acid synthase ( FAS) gene expression, we assessed an adiposity index, leptin and FAS mRNA levels, FAS activity in perirenal adipose tissue and serum leptin concentration in rats aged 1, 2, 3, 6 and 20 months. The results indicate that there are two distinct phases of changes in perirenal white adipose tissue leptin mRNA level and serum leptin concentration. The first phase, between 1 and 3 months of the animals’ lives, was characterized by a strong positive correlation between adiposity index and leptin mRNA level as well as serum leptin concentration. In the second phase (over 3 months) no significant changes of leptin mRNA and serum concentration occurred. A close correlation between the age-induced increase of leptin mRNA abundance and serum leptin concentration and the age-induced suppression of FAS gene expression in the same tissue was observed. This suggests that the changes of FAS gene expression occur in response to serum leptin concentration and that in mature rats the high level of ob gene expression and consequently the high leptin concentration protect the white adipose tissue cells against fat overload by two independent mechanisms: (a) preventing an increase of food intake through the leptin action on the hypothalamus; (b) inhibiting FAS gene expression and consequently decreasing the rate of lipogenesis.

Protein-Losing Enteropathy is Associated with Peritoneal Functional Abnormalities in Peritoneal Dialysis Patients

To evaluate the relationship between acquired peritoneal transport disorders and the presence of protein-losing enteropathy (PLE), and their contribution to the protein malnutrition in peritoneal dialysis (PD) patients. We studied 31 clinically stable PD patients that received a fat overload diet for 3 days. We measured intestinal absorption of fecal fat (normal < 6 g/24-hour stool) and nitrogen (normal < 2 g/24-hr stool), intestinal protein permeability [fecal clearance of alpha1-antitrypsin (Calpha1AT) (normal < 12 mL/24-hr stool)], and nutritional markers [normalized protein nitrogen appearance (nPNA), half-life medium-term proteins, and body mass index]. Peritoneal solute transport was measured by mass transfer coefficient (MTC), and water transport by peritoneal ultrafiltration (UF) capacity. To define protein maldigestion it was necessary to find high fecal nitrogen values with normal Calpha1AT; PLE was defined when both values were elevated. High fecal nitrogen (mean 2.1+/-1 g/24-hr stool) and fat (mean 5.8+/-3.6 g/24-hr stool) were found in 15 patients; 6 patients had high Calpha1AT levels (PLE). These 6 patients showed a worse nutritional status: lower albumin (3.57+/-0.57 g/dL vs 3.98+/-0.38 g/dL, p < 0.05) and transferrin (243+/-70 mg/dL vs 272+/-44.3 mg/dL, p < 0.05), as well as lower triglycerides (131.3+/-31.7 mg/dL vs 187+/-116 mg/dL, p< 0.05). Higher urea MTCs were found in 10 patients, normal in 7, and lower in 14. Higher creatinine MTCs were found in 8 patients, normal in 15, and lower in 8. Normal peritoneal UF capacity was found in 25 and lower in 6 patients. These 6 patients showed higher urea and creatinine MTCs and Calpha1AT. A positive linear correlation between Calpha1AT, urea MTC (r = 0.56, p < 0.01), and creatinine MTC (r = 0.46, p < 0.01) was found. A similar situation occurred between Calpha1AT, fecal fat (r = 0.45, p < 0.05), and fecal nitrogen (r = 0.43, p < 0.05). Thirteen patients with previous history of peritonitis showed higher Calpha1AT than those without peritonitis (10.2+/-8 mL/24-hr stool vs 5.2+/-4.4 mL/24-hr stool, p < 0.05). We confirm that protein and fat malabsorption, maldigestion, and PLE are present in some PD patients. Higher fecal Calpha1AT is associated with malnutrition and poorer showings of the viability markers of peritoneal membrane function.

Enhanced de novo lipogenesis in the leptin-unresponsive pancreatic islets of prediabetic Zucker diabetic fatty rats: role in the pathogenesis of lipotoxic diabetes.

Overaccumulation of fat in pancreatic islets of obese ZDF fa/fa rats is believed to cause beta-cell failure and diabetes. Previously, we demonstrated that ZDF islets have an increased capacity to esterify fatty acids imported via the circulation. Here we examine the capacity of ZDF islets to synthesize fatty acids de novo. Compared with age-matched wild-type (+/+) control islets, acetyl CoA carboxylase (ACC) mRNA was fivefold and sixfold higher and fatty acid synthetase (FAS) was fourfold and sevenfold higher in prediabetic and diabetic ZDF islets, respectively. Incorporation of label from [14C]glucose into lipids was 84% higher in ZDF islets and was not suppressed normally by fatty acids. Chronic hyperleptinemia, induced by adenoviral transfer of leptin cDNA, reduced ACC and FAS mRNA in +/+ islets by 93 and 80%, respectively, but did not decrease the high ACC and FAS expression in islets of fa/fa rats. Recombinant leptin cultured with islets isolated from +/+ rats lowered ACC and FAS expression by 66 and 47%, respectively, but had no effect in fa/fa islets. We conclude that de novo lipogenesis in islets is controlled by leptin and remains low in leptin-responsive islets. It is increased in leptin-insensitive fa/fa islets, contributing to the fat overload that leads to beta-cell dysfunction and diabetes.

Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study

Objective : To compare the feasibility of treatment, safety, and toxicity of intravenous amphotericin B deoxycholate prepared in either glucose or intralipid for empirical antimycotic treatment of neutropenic cancer patients.Design...

Incidence and ultrasonographic patterns of hepatic steatosis in the elderly

A retrospective ultrasonographic study was conducted to assess the incidence of hepatic steatosis in subjects in the age range 18-92 years, to evaluate the prevalence of hepatic steatosis in different age groups (Group A: age range 65-92 years; Group B: age range 18-64 years and to show the related ultrasonographic patterns (diffuse homogeneous, ultrasound attenuation, skip areas, skip areas and ultrasound attenuation, focal or irregular). The occurrence of hepatic steatosis (24.8% in the whole study population) showed a statistically significant difference (p < 0.005) between Groups A (17.7%) and B (28.4%). Besides, the prevalence of various ultrasonographic patterns of hepatic steatosis was different. In the elderly group A the incidence of ultrasound attenuation and focal or irregular distribution was almost doubled. The lower occurrence of hepatic steatosis in the elderly may be an expression of a natural selection, since steatosis is generally associated with factors of vascular risk and chronic liver diseases, which may cause a reduced survival. The greater prevalence of ultrasound attenuation pattern in the elderly may be an expression of advanced steatosis and/or micro-irregular distribution of fatty hepatocytes. The high incidence of focal or irregular pattern may depend on vascular alterations of the liver causing focal fat overload.

Critical Care Pharmacotherapy

During recent years, research in critical care medicine has focused on the role of the gastrointestinal tract in the pathogenesis of multiple organ failure and nosocomial infection, and on preventive measures. Gram-negative bacterial overgrowth of the oropharynx and stomach has been proved to be a cause of nosocomial pneumonia. Topical application of antibiotics into the oropharynx and stomach, and preservation of gastric acidity have been shown to be effective prophylaxis in ventilated patients. Recent studies have demonstrated that gastric alkalinisation is no longer necessary for the prevention of stress ulcer bleeding in critically ill patients. Tissue hypoxaemia, not gastric acidity, is the underlying pathomechanism of stress ulcer bleeding. In experimental investigations, pirenzepine and sucralfate improved gastric mucosal oxygen supply. Both compounds effectively prevent bleeding without increasing gastric pH. In mechanically ventilated patients, significantly lower rates of pneumonia occur with both of these drugs compared with antacids or histamine H2-receptor antagonists. Topical antibiotics (selective digestive decontamination) are most effective in patients with alkaline gastric juice, but of only marginal clinical relevance in those with acidic gastric contents. Isoflurane, propofol and clonidine have been recently investigated for sedation of ventilated patients. Isoflurane may lead to fluoride accumulation after more than 1 day. Propofol dosage has to be increased more often after 4 to 7 days, leading to fat overload and significantly increased costs. Clonidine was highly effective in patients with 'sympathetic overshoot', e.g. those experiencing alcohol or opioid withdrawal. Wound infections are an important problem in burn patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravascular Coagulation and Osteonecrosis

Current evidence suggests that intravascular coagulation (IC), an intermediary mechanism, is the most likely final common pathway by which intraosseous fat embolism causes nontraumatic osteonecrosis (ON). Stage 1A lesions (fatty osteocytic necrosis) appear to progress to classic Stage 1B lesions (ischemic degeneration of necrotic osteocytes and adipocytes) when the ischemic threshold is exceeded by absolute subchondral fat overload with insufficient local clearance of procoagulants, especially tissue thromboplastin. The result is vascular stasis, hypercoagulability, endothelial damage (by free fatty acids) and IC, especially if there is coexistent subchondral vasoconstriction and impaired secondary fibrinolysis. Osteonecrosis can be produced in animals by IC, which begins in the vulnerable subchondral microcirculation (Arthus phenomenon). Cartography (embolic scintimetry with superselective angiography) indicates early complete devascularization of the femoral head, suggesting progressive venous and retrograde arterial thrombosis. Increased plasma fibrinopeptide A and direct histologic evidence of intraosseous thromboses and peripheral hemorrhages further indicate that IC is the final pathway. Best evidence are 51 ON lesions complicating disseminated IC in eight children (Shwartzman phenomenon), with collateral histologic evidence of intraosseous thrombosis and ON.

The Fat Overload Syndrome: Successful Treatment with Plasma Exchange

Excerpt The fat overload syndrome is a rare complication of the intravenous administration of fat emulsion. It is characterized by sudden elevation of the serum triglyceride level associated with f...

Retinal Findings in the Fat Overload Syndrome

Parenteral hyperalimentation using lipid is considered an effective and relatively safe method of delivering essential nutrients to patients unable to tolerate enteral feedings. Although the fat overload syndrome is a well-recognized complication of intravenous lipid therapy, its ocular manifestations have not been previously described, to our knowledge.1-3 Report of a Case. —A 38-year-old Hispanic man was admitted to a community hospital with fever, cough, wheezing, and a lung infiltrate. He was initially treated with bronchodilators, antibiotics, and supplemental oxygen. On the second hospital day parenteral hyperalimentation, which included a 20% fat emulsion infusion (Liposyn II, Abbott Laboratories, Chicago, Ill) was initiated. During the next 5 days the patient was iatrogenically lipid overloaded, receiving 11L of 20% Liposyn II (6.2 g of fat per kilogram of body weight per day). The maximum recommended dosage of Liposyn II is 3.0 g of fat per kilogram of body weight per day. During

Lipid tolerance in children receiving long-term parenteral nutrition: a biochemical and immunologic study.

The effect of intravenously administered lipids (intralipid) on immunologic function, complement, and coagulation was prospectively studied over 1 year in 15 children. The mean age of the children was 52.4 +/- 37.9 months; they had received total parenteral nutrition for an average of 3 years. Immunoglobulins (IgA, IgM, IgG), coagulation studies (platelets, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrinogen degradation products, factor V) and components of complement (C3, C4, and CH100) were analyzed. Activation of monocytes by opsonized zymosan was measured by chemiluminescence and compared with that of normal control subjects. The clinically stable children had normal monocyte activation and normal complement levels. The PT and PTT values were significantly increased but improved with increased intralipid dose; other coagulation factors were normal. Acutely sick children, however, had decreased fat tolerance with significantly increased serum triglyceride levels and PT and PTT values; their monocyte activation and complement factors remained normal. These data indicate that the dose of intralipid should be lowered during acute illnesses; we suggest close monitoring of PT and PTT values and of serum triglyceride and cholesterol levels to avoid the fat overload syndrome.

Lysosomal enzyme activity of monocytes/macrophages following incubation with postprandial hyperlipemic serum and its significance for the development of atherosclerosis

Lipid accumulation in macrophages is a prominent feature of the atherosclerotic lesion. Decreased lysosomal function of these cells might play an important role in the pathogenesis of the atherosclerotic foam cell. In this investigation six normal volunteers were fed a meal with a high fat content (68.9% energy, P/S ratio 0.13). The hyperlipidemic postprandial serum was incubated with monocyte derived macrophages. The enzyme activity of cathepsin B, acid cholesterylester-hydrolase and N-acetyl-beta-hydrolase decreased significantly in these cells. Thus, inadequate response in enzyme activity of lysosomal enzymes in case of fat overload might contribute to the development of the atherosclerotic foam cell.