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PubMed1986

Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells.

The effect of a variety of cytokines on lipid metabolism in 3T3 L1 mouse fibroblasts and adipocytes was studied. Uptake of [3H]acetate by adipocytes and heparin-releasable lipoprotein lipase activity was inhibited after treatments of the cells with picomolar concentrations of recombinant human tumor necrosis factor alpha (rHuTNF-alpha), human tumor necrosis factor beta (rHuTNF-beta, also called lymphotoxin), murine interferon-gamma (rMuIFN-gamma), and a human hybrid interferon-alpha [rHuIFN-alpha 2/alpha 1 (Bgl II)]. Recombinant human interferon-gamma (rHuIFN-gamma), natural human colony-stimulating factor (HuCSF), and human interleukin 2 (HuIL-2) had no effect. Similar though less-marked suppression of [3H]acetate uptake by cytokines was seen in 3T3 L1 fibroblasts. Cytokines inhibited the incorporation of [3H]acetate into both membrane and storage lipids in the adipocytes. In addition to blocking lipid uptake and synthesis, rHuTNF-alpha and -beta, and rMuIFN-gamma stimulated the release of free fatty acid into the medium from adipocytes. Binding studies suggest that rHuTNF-alpha and rHuTNF-beta compete for the same cell-surface receptor on 3T3 L1 adipocytes, while rMuIFN-gamma binds to a separate receptor. The binding of rTNF-alpha to both adipocytes and fibroblasts can be significantly enhanced by preexposure of the cells to rMuIFN-gamma. There appear to be both high- and low-affinity receptors for rHuTNF-alpha on adipocytes, whereas fibroblasts exhibit a single class of high-affinity receptors. These results suggest that a variety of structurally distinct cytokines possess lipid mobilization activity, which may be of critical importance to the host in defense against infection or malignancy.

Acetates↗
PubMed2004

Effects of biotin supplementation on peripartum performance and metabolites of Holstein cows.

Fifty-two multiparous Holstein cows were randomly assigned to receive 0 or 20 mg of biotin/d starting at an average of 16 d prepartum and then switched to 0 or 30 mg of biotin/d from calving through 70 d postpartum to determine whether supplemental biotin would affect cow performance, hepatic lipidosis, and plasma metabolites. Mean concentration of biotin in plasma sampled weekly was greater in cows fed biotin (4.3 vs. 9.4 nmol/L). Postpartum dry matter intake as a percentage of body weight (3.9% vs. 4.0%), milk production (35.8 vs. 34.8 kg/d), and milk fat concentrations (3.59% vs. 3.69%) were similar between treatment groups. Milk from biotin-supplemented cows tended to have a greater concentration of protein (2.73% vs. 2.83%). Concentrations of plasma nonesterified fatty acids were lower at wk 2 (652 vs. 413 microEq/mL) and 4 (381 vs. 196 microEq/mL) postpartum in cows fed supplemental biotin. However, mean plasma concentrations of beta-hydroxybutyric acid were not affected by biotin supplementation. Mean concentration of plasma glucose was greater for lactating cows fed supplemental biotin (63.4 vs. 66.6 mg/dL). Biopsies of liver were taken at 2, 16, and 30 d postpartum. The triacylglycerol concentration in liver (wet basis) tended to decrease at a faster rate after d 2 postpartum with biotin supplementation compared with control cows. The potential mechanisms that link improved glucose status and decreased lipid mobilization in cows supplemented with biotin warrant further investigation.

3-Hydroxybutyric Acid↗
PubMed1979

[The effects of non-protein-nitrogen additives on lipid and carbohydrate metabolisms in sheep (author's transl)].

The effects of NPN administration on lipid and carbohydrate metabolisms were investigated in 14 sheep. Blood non-esterified fatty acids (NEFA) are increased by intra-ruminal dosage with urea (10 g), 1 p. 1000 ammonia solution (1 l) or ammonium chloride (17.6 g). Peak values are recorded 3 to 4 hours after the injection. An early rise of NEFA and hyperglycemia are observed when ammonium chloride is injected intra-venously. The time-course of the variations of the different blood constituents (ammonia, glucose, NEFA, urea) as well as the lack of any action following intra-venous urea injections suggest that lipid mobilization is induced by the increased level of blood ammonia. The involvement of a strenghened activity of the sympathetic-adrenal system is evidenced by the increased elimination of urinary catecholamines.

Ammonia↗
PubMed2006

Tissue lipid lowering-effect of a traditional Nigerian anti-diabetic infusion of Rauwolfia vomitoria foilage and Citrus aurantium fruit.

The toxicity and anti-diabetic properties of an aqueous plant extract made by boiling Rauwolfia vomitoria foilage and Citrus aurantium fruits were evaluated in mice. A single dosage corresponding to 70x the human-daily-dose was non-toxic when administered to 6-week-old NMRI lean mice or 6- or 11-week-old C57BL/6J lean mice. Daily treatment of 11-week-old C57BL/KsBom-db (db/db) genetic diabetic mice with a dose corresponding to 10x human-daily-dose for 6 weeks facilitated a significant weight loss as compared to the untreated controls. During treatment, the db/db mice were maintained on the carbohydrate-deficient Altromin C1009 diet. Although the food intake in the treated mice was not statistically significant from that in the controls, the treated animals had significantly higher serum triglyceride contents, suggesting that the treatment induced lipid mobilization from internal stores. Moreover, the fatty acid profile of the eyes from the treated animals showed a significant reduction in total fatty acid content accompanied by a 33% reduction in estimated Stearoyl-CoA desaturase activity (p = 0.039) as compared with controls. The fatty acid mobilization and a protection of the brittle C57BL/KsBom-db pancreas were observed 5 weeks after cessation of treatment when the treated animals were maintained on the poorer Altromin C1009 diet.

Animals↗
PubMed1991

Effect of subacute administration of isoniazid and pyridoxine on lipids in plasma, liver and adipose tissues in the rabbit.

The effect of subacute intraperitoneal administration of Isoniazid (INH) on various lipid parameters was studied in liver and adipose tissue in addition to plasma. In the liver, its effect on various phospholipid fractions was also assessed. The changes in lipid profile reflected INH-induced hepatic steatosis. While pyridoxine alone did not alter any of these lipid parameters, its concurrent administration with INH prevented almost all the INH-induced lipid changes. The enhanced lipid mobilization into liver, and a fall in phosphatidylcholine with a concomitant rise in phosphatidylethanolamine in liver impeding lipoprotein synthesis, might be responsible for the hepatic steatosis. Pyridoxal, a pyridoxine metabolite, might have trapped the primary amine functional group of acetylhydrazine and thus prevented the steatosis.

Adipose Tissue↗
PubMed1988

Relations between plasma non-esterified fatty acid metabolism and body tissue mobilization during chronic undernutrition in goats.

1. Eleven mature goats were offered 140 kJ metabolizable energy/kg per d (M) of lucerne (Medicago sativa) hay-oaten grain (1:1, w/w) for at least 1 month before plasma non-esterified fatty acid (NEFA) kinetics and tritiated water space (TS) were determined. 2. Goats were then fed at M, 0.5 M or 0.25 M for 34 (SE 6) d, at which time the experimental procedures were repeated. 3. Chronic undernutrition resulted in elevated NEFA concentrations and NEFA entry rate, with a tendency for the ratio plasma NEFA:glycerol to increase, suggesting that body-fat mobilization during prolonged underfeeding is due more to decreased lipogenesis and intracellular NEFA re-esterification rather than to increased lipolysis. 4. Plasma NEFA concentrations and NEFA entry rate, as well as being highly correlated with each other, were significantly related to calculated energy balance and body fat losses estimated from changes in live weight and TS. 5. Increases in NEFA entry rate were highly correlated with, and of the same magnitude as, body fat losses, confirming that NEFA kinetics do quantitatively reflect lipid mobilization.

Animals↗
PubMed1975

Changes in metabolite concentration in the plasma, liver and muscle of feed restricted Japanese quail exposed to cold.

Quail fed ad libitum and 50% ad libitum were cold exposed for several weeks, during time control quail remained at 21 degrees C. The concentration of plasma glucose, FFA, and uric acid, tissue glycogen and carcass fat content was measured at the end of the cold exposure period. Quail fed ad libitum showed no significant change in the levels of plasma and tissue metabolites, or the carcass fat content, following cold exposure. The feed consumption by the cold exposed quail increased, and the mean body weight showed little variation from that of the controls. Feed restricted quail which were cold exposed lost significantly more weight, and had a lower ranked fat content than their controls. Whereas feed restriction caused a lowering of the liver glycogen concentration in both treatment groups, muscle glycogen levels were higher than in quail fed ad libitum. However, cold exposure was not accompanied by a change in muscle and liver glycogen levels in feed restricted quail. Feed restricted quail at 21 degrees C were hypoglycaemic and hyperlipaemic compared to quail fed ad libitum, but cold exposed feed restricted quail had a much higher plasma glucose concentration than the controls. The ranked carcass fat content was inversely related to plasma FFA level in both control and cold exposed feed restricted quail. It is suggested that both a glycolytic and lipid mobilizing response to cold is obtained in quail whose body reserves are not spared from catabolism by adequate dietary nutrient absorption, and the possibility of gluconeogenesis from precursors produced by proteolysis is indicated.

Adaptation, Physiological↗
PubMed1999

ADSA Foundation Scholar Award. Biology of dairy cows during the transition period: the final frontier?

The transition period, from 3 wk before to 3 wk after parturition, is critically important to health, production, and profitability of dairy cows. Most health disorders occur during this time. Compared with other stages of the lactation cycle, relatively little is known about fundamental biological processes during the transition period. The regulation and coordination of lipid metabolism among adipose tissue, liver, gut, and mammary gland are key components of the adaptations to lactation. Lipid accumulation in liver may contribute to health disorders and decreased milk production. Knowledge of key control points in hepatic metabolism of long-chain fatty acids is lacking, as is an understanding of the metabolic effects of hormones, growth factors, and cytokines that mediate stress. Recent evidence indicates that supplemental fats or restricted intakes before parturition can induce a coordinated set of metabolic changes in metabolism of long-chain fatty acids, including peroxisomal beta-oxidation, perhaps mediated by peroxisome proliferator-activated receptors. Estimates of the mixture of fuels constituting metabolizable energy in cows during the early postpartum period suggest that supply of amino acids and glucogenic compounds may be under proposed optima, whereas ketogenic and lipogenic compounds and long-chain fatty acids may be in excess. Because dietary fat does not suppress body lipid mobilization, during the early postpartum period supplemental fat may further imbalance the mixture of fuels and lead to decreased dry matter intake. Increased understanding of the biology of the transition period should decrease health problems and increase profitability of dairy cows.

Adipose Tissue↗
PubMed2006

Peroxisome proliferator-activated receptor delta promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage.

Significant attention has focused on the role of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, recent advances have identified triglyceride-rich lipoproteins [e.g., very LDL (VLDL)] as independent risk predictors for this disease. We have previously demonstrated peroxisome proliferator-activated receptor (PPAR)delta, but not PPARgamma, is the major nuclear VLDL sensor in the macrophage, which is a crucial component of the atherosclerotic lesion. Here, we show that, in addition to beta-oxidation and energy dissipation, activation of PPARdelta by VLDL particles induces key genes involved in carnitine biosynthesis and lipid mobilization mediated by a recently identified TG lipase, transport secretion protein 2 (also named desnutrin, iPLA2zeta, and adipose triglyceride lipase), resulting in increased fatty acid catabolism. Unexpectedly, deletion of PPARdelta results in derepression of target gene expression, a phenotype similar to that of ligand activation, suggesting that unliganded PPARdelta suppresses fatty acid utilization through active repression, which is reversed upon ligand binding. This unique transcriptional mechanism assures a tight control of the homeostasis of VLDL-derived fatty acid and provides a therapeutic target for other lipid-related disorders, including dyslipidemia and diabetes, in addition to coronary artery disease.

Animals↗
PubMed2001

Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy.

Multinuclear ((1)H, (13)C, and (31)P) magnetic resonance spectroscopy are applied to the biochemical characterization of the total lipid fraction of healthy and neoplastic human brain tissues. Lipid extracts from normal brains, glioblastomas, anaplastic oligodendrogliomas, oligodendrogliomas, and meningiomas are examined. Moreover, the unknown liquid content of a cyst adjacent to a meningioma is analyzed. Two biopsies from glioblastomas are directly studied by (1)H-NMR without any treatment (ex vivo NMR). The (1)H- and (13)C-NMR analysis allows full characterization of the lipid component of the cerebral tissues. In particular, the presence of cholesteryl esters and triglycerides in the extracts of high grade tumors is correlated to the vascular proliferation degree, which is different from normal brain tissue and low grade neoplasms. The (31)P spectra show that phosphatidylcholine is the prominent phospholipid and its relative amount, which is higher in gliomas, is correlated to the low grade of differentiation of tumor cells and an altered membrane turnover. The ex vivo (1)H-NMR data on the glioblastoma samples show the presence of mobile lipids that are correlated to cell necrotic phenomena. Our data allow a direct correlation between biochemical results obtained by NMR and the histopathological factors (vascular and cell proliferations, differentiation, and necrosis) that are prominent in determining brain tumor grading.

Brain Chemistry↗
PubMed2002

Sublethal effects of exposure to chemical compounds: a cause for the decline in Atlantic eels?

Because of their unusual life cycle, American and European eels (Anguilla rostrata Lesueur and A. anguilla L.), are particularly exposed to pollutant effects. Because silver eels fast when they leave the freshwater system, the transoceanic migration forces them to constitute energy reserves in the form of muscle lipids, that are needed for successful spawning. Using species biological data, toxicological and ecotoxicological information, hypotheses are given to assess the contribution of pollution from freshwater sources to the recorded decline in the American and European eels fisheries since the 1980s. This paper first describes the lipid storage problems and the relative migratory capacities. Then several studies on the accumulation of xenobiotics in various anatomical compartments, on the biological half-lives of these compounds, and on their sublethal toxicity, are reviewed. During migration, lipid mobilization returns persistent lipophilic pollutants back into circulation, these being concentrated particularly in gonads at the crucial time of gametogenesis. Extrapolation of toxicological analysis (individual physiology) to the population level (spawning success) suggests that the quality of future spawners leaving freshwaters is one of the prime factors for the conservation of this threatened species.

Animals↗
PubMed1991

Effects of exogenous intravenous glucose on plasma glucose and lipid homeostasis in anesthetized children.

Whether or not intravenous glucose administration during pediatric anesthesia is necessary remains a controversial issue. The current study was designed to investigate the effect of glucose infusion on concentrations of plasma glucose, nonesterified fatty acids (NEFA), triglycerides, ketone bodies, and insulin and to determine whether the use of solutions containing less than 5% glucose would maintain physiologic plasma glucose concentrations during tympanoplasty lasting about 6 h. Forty-five children aged between 1.5 and 9 yr were divided randomly into three groups of 15 patients each to receive the following intravenous solutions: LR groups, lactated Ringer's solution (LR) alone; D2LR group, 2% glucose in LR; and D5LR group, 5% glucose in LR. All fluids were infused at a rate of 6 ml.kg-1.h-1 until 1 h after anesthesia. In the LR group, the plasma glucose concentrations remained unchanged perioperatively compared with basal values, whereas in the D2LR group they showed a gradual increase during surgery but remained normoglycemic. On the other hand, in the D5LR group, the plasma glucose concentrations increased markedly both during and after the operation. Furthermore, 3 of 15 patients showed hyperglycemia of more than 300 mg.dl-1 during anesthesia. There was no evidence of lipid mobilization or impaired secretion of insulin, since plasma NEFA, triglycerides, ketone bodies, and insulin remained within normal concentration ranges throughout the sample period in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed2003

Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry.

Herpes simplex virus (HSV) entry requires the interaction of glycoprotein D (gD) with a cellular receptor such as herpesvirus entry mediator (HVEM or HveA) or nectin-1 (HveC). However, the fusion mechanism is still not understood. Since cholesterol-enriched cell membrane lipid rafts are involved in the entry of other enveloped viruses such as human immunodeficiency virus and Ebola virus, we tested whether HSV entry proceeds similarly. Vero cells and cells expressing either HVEM or nectin-1 were treated with cholesterol-sequestering drugs such as methyl-beta-cyclodextrin or nystatin and then exposed to virus. In all cases, virus entry was inhibited in a dose-dependent manner, and the inhibitory effect was fully reversible by replenishment of cholesterol. To examine the association of HVEM and nectin-1 with lipid rafts, we analyzed whether they partitioned into nonionic detergent-insoluble glycolipid-enriched membranes (DIG). There was no constitutive association of either receptor with DIG. Binding of soluble gD or virus to cells did not result in association of nectin-1 with the raft-containing fractions. However, during infection, a fraction of gB but not gC, gD, or gH associated with DIG. Similarly, when cells were incubated with truncated soluble glycoproteins, soluble gB but not gC was found associated with DIG. Together, these data favor a model in which HSV uses gB to rapidly mobilize lipid rafts that may serve as a platform for entry and cell signaling. It also suggests that gB may interact with a cellular molecule associated with lipid rafts.

Animals↗
PubMed2003

Post-exercise increase of lipid oxidation after a moderate exercise bout in untrained healthy obese men.

The aim of the study was to examine whether a moderate exercise increases the utilization of fatty acids during the recovery period in obese men. Six healthy obese participated in a randomized crossover investigation, one with exercise and one without exercise. At 8 a. m., the subjects had a standardized breakfast and they rested in a sitting position for 3 hours. The subjects were maintained in the sitting position for 4 additional hours in one session. In a second session, they exercised for 60 min at 50 % of their VO(2) max and then returned to the sitting position for 3 hours. Respiratory exchange ratio (RER) values were calculated by indirect calorimetry. During the resting session, plasma non-esterified fatty acids (NEFA) and glycerol concentrations rose progressively, whereas RER progressively decreased. During the exercise, plasma catecholamines, NEFA, glycerol, growth hormone and cortisol levels and RER increased while insulin decreased. During the recovery, plasma NEFA increased and glycerol decreased. During the first hour of recovery, RER values were lower and fatty acid utilization higher than during the same period of the resting session. The study shows that exercise induces modifications in hormonal factors promoting lipid mobilization and suggests that exercise provide substantial amounts of NEFA for muscle oxidation during recovery from an exercise bout in obese subjects.

Adult↗
PubMed1993

Differential effects of somatostatin-14 and somatostatin-25 on carbohydrate and lipid metabolism in rainbow trout Oncorhynchus mykiss.

Previous studies have indicated that teleost fish appear to have two somatostatin genes. In salmonid fish, it is purported that gene I encodes for somatostatin-14 (SS-14), while gene II encodes for somatostatin-25 (sSS-25). In the present study, the physiological effects of SS-14 and sSS-25 on carbohydrate and lipid metabolism in rainbow trout, Oncorhynchus mykiss, were evaluated by in vivo administration of hormone and measuring resulting levels of specific metabolites and hormones present within tissues and plasma. Somatostatin-14 administration caused hyperglycemia without affecting liver glycogen content and increased plasma fatty acid (FA) levels in association with enhanced activity of the lipid mobilizing enzyme, triacylglycerol lipase (TG lipase). Somatostatin-14 injection also resulted in reduced hepatic glucose-6-phosphate dehydrogenase activity, which may indicate a decrease in glucose channeling through the pentose phosphate shunt. In addition, SS-14 reduced plasma glucagon concentration, while having no effect on plasma insulin levels. Salmon SS-25 elevated plasma glucose levels in association with reduced glycogen content and resulted in increased plasma FA levels accompanied by increased hepatic TG lipase activity. Salmon SS-25 injection also resulted in a reduction in plasma glucagon and insulin levels. These results indicate that SS-14 and sSS-25 are important regulators of carbohydrate and lipid metabolism in rainbow trout and that modulation of metabolic activity by these peptides may be accomplished, in part, by alterations in insulin and glucagon levels circulating in the plasma.

Animals↗
PubMed1993

Editing 13C-NMR spectra of membranes.

We report the carbon-13 'magic-angle' sample-spinning nuclear magnetic resonance (NMR) spectra of several lipid-water systems, under a variety of radiofrequency excitation conditions. Our results show that complex lipid or membrane spectra can be greatly simplified by using 'spectral editing' techniques. For example, in a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-water mesophase, the glycerol (C-1, C-2 and C-3) carbons are readily distinguished from the headgroup C alpha, C beta and C gamma carbons, on the basis of their mix-time behavior in a cross-polarization (CP) experiment, while in the more complex DMPC/cholesterol-water system, many of the more rigid cholesterol carbon resonances can be edited from the phospholipid peaks. In very complex systems, such as human myelin membranes, editing permits the unambiguous observation of the mobile lipid headgroup carbon resonances, as well as the much more rigid sterol ring carbons. We also report the observation of a large differential CP due to C-H vector 'magic-angle' orientational effects in the DMPC/desipramine system. Thus, both motional or orientational reduction of the C-H dipolar interaction can lead to considerable simplifications of complex membrane spectra, and are of interest from both spectral assignment and membrane dynamics aspects.

Cell Membrane↗
PubMed1997

The swine as a model for studying exercise-induced changes in lipid metabolism.

The swine has many similarities to humans, making it an excellent research model in which to study the role of exercise on lipid metabolism. Swine adapt to exercise-training by increasing muscle oxidative enzymes, maximal stroke volume, cardiac output, VO2max, and high density lipoprotein cholesterol levels, while decreasing total cholesterol levels and resting heart rate. The lipoprotein profile of swine and humans is also similar, and low density lipoprotein is the major cholesterol transporting lipoprotein in both species. Several studies in swine report conflicting results on the effect of exercise-training on lipoprotein profile and atherosclerotic lesion appearance. This may result from differences in total exercise time between the studies. With sufficient total exercise, atherosclerosis was reduced and high density lipoprotein cholesterol levels were increased. Exercise may also play a role in reducing obesity, a risk factor for cardiovascular disease, by enhancing lipid mobilization from adipocytes. Recent research suggests that swine adipocyte sensitivity to adenosine, a locally-produced antilipolytic agent, is reduced after exercise treatment. Cellular mechanisms responsible for this metabolic change include a reduction in adenosine A1 receptor number. Current studies are examining the transport of extracellular cyclic AMP from adipocytes and its role as a potential adenosine precursor.

Animals↗
PubMed1983

Rehydration using solutions with and without glucose before emergency abdominal surgery in children.

The metabolic effects of six different solutions used for rehydration were studied in 88 children before emergency abdominal surgery. A volume corresponding to 5% of the body weight was given i.v. during 4 h (12.5 ml . kg-1 . h-1) between admission and surgery. The different solutions were: low glucose electrolyte solution (LGE), Rehydrex 2.5%, Rehydrex 5% containing 0.9, 2.5 and 5.0% glucose, respectively, Ringer, Ringer lactate and Ringerdex (30 mmol acetate . l-1). Venous blood samples were drawn before and after rehydration and analysed for glucose, insulin, alanine, 3-hydroxybutyrate (3-HB), non-esterified fatty acids (NEFA), glycerol and base excess. Before rehydration the plasma concentrations of NEFA, glycerol and 3-HB were elevated, while that of alanine was decreased. Plasma levels of NEFA and 3-HB remained unchanged, whereas glucose and insulin decreased after rehydration with glucose-free solutions, i.e. Ringer, Ringer lactate and Ringerdex. With solutions containing glucose the concentrations of NEFA and 3-HB decreased significantly. With Rehydrex 5% hyperglycaemia and hyperinsulinaemia were observed. Rehydration using LGE and especially Rehydrex 2.5% resulted in decreased lipid mobilization and ketonaemia without concomitant marked increase of glucose and insulin. LGE and Rehydrex 2.5% thus appeared to be the most appropriate solutions in a situation where moderate dehydration had to be corrected during a short period of time before emergency abdominal surgery.

Abdomen, Acute↗