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PubMed2000

Nutritional support for treatment of hepatic lipidosis in a llama.

A 3-year-old female llama that was 3 months into her first lactation and 10 weeks pregnant was evaluated for anorexia of 24 hours' duration. On physical examination, the llama was in lateral recumbency, bradycardic, tachypneic, and hyperthermic. Palpation per rectum confirmed the presence of a possible dry fecal mass in the spiral colon. A tissue biopsy specimen of the liver was obtained, and histologic examination revealed moderate diffuse lipid accumulation within the hepatocytes. Lactated Ringer's solution was administered for rehydration, and partial parenteral nutrition was then initiated. Hepatic lipidosis is a disease characterized by abnormal accumulation of lipid in the liver and is associated with high mortality in camelids. Anorexia associated with hepatic lipidosis promotes further lipid mobilization and fatty infiltration of the liver. Partial parenteral nutrition with enteral supplementation may be used to maintain adequate energy intake and minimize further lipid mobilization. The distinctive metabolism of camelids may require higher amino acid supplementation relative to nonprotein calories in parenteral solutions than those traditionally provided to other species. Treatment with insulin may be effective

Animals↗
PubMed1984

Interplay of alpha-2 and beta adrenoceptors in the control of free fatty acid release from bone marrow adipose tissue.

The effect of various adrenergic drugs on the free fatty acid (FFA) output from bone marrow was studied in dog tibia after constant flow autoperfusion of the nutrient artery by femoral arterial blood and cannulation of the nutrient vein. Clonidine, an alpha-2 adrenoceptor agonist, inhibited the isoproterenol-induced FFA outflow from bone marrow adipose tissue. This effect was suppressed by the alpha-2 antagonists (phentolamine and yohimbine). Moreover, clonidine inhibited the FFA outflow initiated by theophylline associated with adenosine deaminase. When the alpha-2 sites were blocked by phentolamine or yohimbine, epinephrine exerted an enhanced effect on FFA outflow in comparison with its effect when infused alone. These in vivo experiments clearly demonstrate that alpha-2 adrenoceptor stimulation is able to inhibit beta-stimulated or theophylline plus adenosine deaminase-promoted lipid mobilization from bone marrow fat stores. The simultaneous stimulation of alpha-2 and beta adrenoceptors initiated by epinephrine could be responsible for the weaker lipid-mobilizing effect of the endogenous catecholamine. It is concluded that adrenoceptors are operative in bone marrow adipose tissue and control FFA outflow in physiological conditions. Moreover, the existence of an interplay between alpha-2 and beta adrenergic effects in in vivo conditions is demonstrated.

Adenosine Deaminase↗
PubMed2006

Beta-adrenergic and atrial natriuretic peptide interactions on human cardiovascular and metabolic regulation.

CONTEXT: Atrial natriuretic peptide (ANP) has well-known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans. OBJECTIVE: The objective of the study was to determine the metabolic and cardiovascular interaction of beta-adrenergic receptors and ANP. DESIGN: This was a crossover study, conducted 2004-2005. SETTING: The study was conducted at an academic clinical research center. PATIENTS: PATIENTS included 10 healthy young male subjects (body mass index 24 +/- 1 kg/m2). INTERVENTION: We infused iv incremental ANP doses (6.25, 12.5, and 25 ng/kg.min) with and without propranolol (0.20 mg/kg in divided doses followed by 0.033 mg/kg.h infusion). Metabolism was monitored through venous blood sampling, im, and sc microdialysis and indirect calorimetry. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. MAIN OUTCOME MEASURES: Venous nonesterified fatty acid, glycerol, glucose, and insulin; and microdialysate glucose, glycerol, lactate, and pyruvate were measured. RESULTS: ANP increased heart rate dose dependently. beta-Adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum nonesterified fatty acid and glycerol concentrations. The response was not suppressed with propranolol. Venous glucose and insulin concentrations increased with ANP, both without or with propranolol. ANP induced lipid mobilization in sc adipose tissue. In skeletal muscle, microdialysate lactate increased, whereas the lactate to pyruvate ratio decreased, both with and without propranolol. Higher ANP doses increased lipid oxidation, whereas energy expenditure remained unchanged. Propranolol tended to attenuate the increase in lipid oxidation. CONCLUSIONS: Selected cardiovascular ANP effects are at least partly mediated by beta-adrenergic receptor stimulation. ANP-induced changes in lipid mobilization and glycolysis are mediated by another mechanism, presumably stimulation of natriuretic peptide receptors, whereas substrate oxidation might be modulated through adrenergic mechanisms.

Adipose Tissue↗
PubMed1995

Enhancement of melphalan toxicity by octanol in ovarian adenocarcinoma cell lines: effects of altered cell-cell communication, glutathione levels, and plasma membrane fluidity.

A2780 and COLO-316 ovarian adenocarcinoma cell lines were exposed to 1.0 mM 1-octanol for 12 hr in order to evaluate the potential effects of inhibition of gap junction-mediated intercellular communication (GJIC) on cellular responses to the chemotherapeutic drug melphalan. Other cellular endpoints relevant to drug-resistance mechanisms which were monitored after treatments included cellular glutathione levels, glutathione S-transferase activity, mitochondrial membrane potential, and plasma membrane lipid mobility. In cells which were sensitive to melphalan, octanol enhanced melphalan toxicity in the GJIC-competent (A2780/S) but not GJIC-incompetent (COLO-316/S) sensitive cells. Although octanol increases plasma membrane lipid mobility in A2780/S and COLO-316/S, it appears that enhancement of A2780/S sensitivity to melphalan may be due to inhibition of GJIC. In melphalan-resistant cells (A2780/R and COLO-316/R), 1.0 mM octanol treatment for 12 hr combined with melphalan reversed the resistance of the cells to the drug. Therefore, alterations in cellular glutathione metabolism and effects on the plasma membrane in addition to uncoupling of GJIC may be involved in sensitizing communication-competent and communication-incompetent resistant cells because COLO-316/R lacks gap junction-mediated intercellular communication. Further, analysis of mitochondrial membrane potential provided an index of acquired drug resistance and the efficacy of melphalan and combined octanol/melphalan toxicity.

1-Octanol↗
PubMed1995

Electron spin resonance studies of acyl chain motion in reconstituted nicotinic acetylcholine receptor membranes.

The electron spin resonance spectra of spin-label positional isomers of stearic acid (n-SASL) incorporated into nicotinic acetylcholine receptors (nAcChoR) reconstituted into dioleoylphosphatidylcholine (DOPC) were deconvoluted into bilayer- and protein-associated components by subtraction under conditions of slow exchange. The selectivity of n-SASL (n = 6, 9, 12, and 14) for the lipid-protein interface of the nAcChoR was threefold greater than that of DOPC and independent of the spin label position. The temperature at which exchange became apparent as judged from lineshape broadening of the mobile lipid component spectrum was dependent upon the position of the spin-label moiety; near the bilayer center, exchange broadening occurred at lower temperatures than it did closer to the lipid headgroup. This suggests that the lipid headgroup region of boundary lipids is relatively fixed, whereas its acyl chain whips on and off the protein with increasing frequency near the bilayer center. Motions on the microsecond time scale were examined by microwave power saturation. Each n-SASL saturated more readily when incorporated into vesicles containing the nAcChoR than when in pure DOPC liposomes. Therefore, lipid mobility is perturbed by the nAcChoR on the microsecond time scale with an apparent magnitude that is relatively modest, probably due to exchange on this time scale.

Animals↗
PubMed1990

Biological effects of synthetic AKH in Manduca sexta and estimates of the amount of AKH in corpora cardiaca.

Dose-response curves were measured with synthetic Manduca adipokinetic hormone (AKH) for glycogen phosphorylase activation in larvae and for lipid mobilization in adults. Both responses are known hormonal functions in Manduca sexta. In ligated larvae, full activation of glycogen phosphorylase was achieved with 0.1 pmol and half-maximal activation with 0.03-0.04 pmol. Maximal lipid mobilization in adults required 10 pmol and half-maximal mobilization 0.15 to 0.2 pmol, respectively. An estimate of AKH content of corpora cardiaca from M. sexta was gained by comparing the dose-response curves for synthetic Manduca AKH with curves from gland extracts. Corpora cardiaca extracts were also quantitated by high performance liquid chromatography. According to both estimates corpora cardiaca of adults contain 10-20 pmol AKH per pair, while a pair of larval corpora cardiaca contains 0.7-2 pmol.

Adipose Tissue↗
PubMed1992

Decreased growth hormone levels in the catabolic phase of severe injury.

BACKGROUND: Human growth hormone (hGH) is a potent anabolic agent, which has profound effects on protein, carbohydrate, and lipid metabolism. The role of this primarily anabolic hormone in the severe catabolic state of trauma is not known. METHODS: In a group of young, obese, and elderly patients with multiple traumas, plasma hGH levels were measured in the catabolic "flow" phase of injury, once before and then after 4 to 6 days of nutritional support sufficient to match their initial loss of calories and nitrogen. RESULTS: A decreased hGH level was noted in the hyperglycemic and hypercatabolic injured state, particularly in victims of trauma who were young and not obese, compared to respective volunteers. A significant (p = 0.025) inverse relationship was observed between age and plasma hGH levels in this group of patients who had experienced trauma. Nutritional therapy improved the protein and fat metabolism but could not reverse to the normal state. In young patients who had experienced trauma and who were not obese, the hGH levels were significantly improved because of dietary intake, whereas in elderly patients or patients who were obese no change was noted. CONCLUSION: These results are consistent with less lipid mobilization and inefficient utilization of fatty acids in the elderly patients or patients who were obese who had abundant fat sources to spare. Elevation of hGH level by exogenous administration may improve the nitrogen economy and lipid mobilization, particularly so in the elderly patients or patients who were overweight. Our study supports the view that provision of adequate nutrition with daily administration of human hGH in the first week after trauma would enhance the metabolic status of the patient, resulting in reduced morbidity and earlier discharge from the hospital.

Adult↗
PubMed1997

Induction of magnetic resonance-visible lipid in a transformed human breast cell line by tetraphenylphosphonium chloride.

Proton magnetic resonance spectroscopy (1H MRS) and DNA flow cytometry were used to monitor the effects of the cationic lipophilic phosphonium salt and potential antineoplastic agent tetraphenylphosphonium chloride (TPP) on the transformed human breast cell line HBL-100. TPP treatment for 48 hr was cytostatic at low concentrations and cytotoxic at higher concentrations with an IC50 of 55 microM as measured by Trypan blue exclusion. At micromolar concentrations, TPP caused a significant increase in the methylene MR signal arising from mobile lipid as measured by the ratio of the lipid CH2 peak height to either the CH3 peak height (internal referencing) or the peak height for p-aminobenzoic acid (PABA) as an external reference in a co-axial capillary within the sample. Over the same concentration range, TPP caused a slowing of passage through S phase as demonstrated by a significant depletion of cells in G2/M phase with a concurrent but non-significant increase in cells in S. Time-dependent increases in MR-visible lipid were observed with 2 microM TPP treatment, and the removal of TPP from the culture medium caused no significant reduction in mobile lipid. Two-dimensional 1H-1H COSY spectra of TPP-treated HBL-100 cells revealed concentration-dependent increases in cross-peak volume ratios arising from lipid acyl chains relative to both internal (lysine, polyamines) and external (PABA) standards. Increases in choline and glycerophosphocholine cross-peak volume ratios were observed, indicating that the catabolism or rearrangement of phospholipids may be responsible for the observed MR-visible lipid increases.

Adult↗
PubMedDate not supplied

[Lipid metabolism in severely acute diarrheic disease in infants].

In a group of 34 infants with serious acute diarrheic disease, the authors study the total lipids, total and esterified cholesterol, triglycerides and lipidogram, in the acute phase of the disease and at a 10-day-interval from the first determination. Triglycerides have constantly increased values both at admittance and at the second determination, as a consequence of lipid mobilization in acute stage. This process continues due to the hypolipidic and hypocaloric diet. Esterified fraction of cholesterol has initially important decreases, tending to become normal in the interval studies, more evident in the healthy infant. Total lipids are increased in 10.5% of the cases and the lipidogram shows an increase of alpha-lipoproteins and prebeta-lipoproteins in 10.5% and 17.5% respectively of the cases in the first determination.

Acute Disease↗
PubMed1998

Application of proton chemical shift imaging in monitoring of gamma knife radiosurgery on brain tumors.

Our objective was to assess proton chemical shift imaging for potential clinical application in monitoring response to gamma knife radiosurgery. Twenty-five proton chemical shift imaging studies and conventional magnetic resonance images were performed on six patients with intracranial tumors. The peak areas of N-acetylaspartate, choline-containing compounds (Cho), creatine, and lipids were calculated and normalized to N-acetylaspartate in the contralateral hemisphere. The spectra from the lesion before treatment showed a relatively high Cho peak, reported as a characteristic spectrum of tumors. Tumor size and Cho level after radiosurgery did not increase except in two cases. In these cases, radiation necrosis was observed with elevated Cho and a mobile lipid peak. Stable or decreased Cho seems to suggest a loss of tumor viability, and changes in Cho indicate the effectiveness of radiosurgery. Increasing Cho and the appearance of the mobile lipid peak may distinguish radiation necrosis from recurrent tumors, which cannot be distinguished by magnetic resonance imaging.

Adolescent↗
PubMed1991

[The effect of alpha adrenergic agents on lipolysis in rat adipose tissue; the effect of nonselective alpha adrenomimetics and alpha adrenolytics in an experiment in vitro].

It is now generally accepted, that in most of the animal species the adrenergic control of lipolysis from adipose tissue is mediated by adrenergic beta 1 and alpha 2 receptors. Therefore, the problem we deal with in this article is concerned with the role of alpha adrenergic receptors in lipolysis in the rat adipose tissue because only in this species the function of alpha adrenergic receptors in lipolysis is still not clear. In in vitro experiments with epididymal adipose tissue of adult rats (where we followed up the release of free fatty acids into the albumin medium) we found: 1) Alpha adrenergic blocking agents phentolamine and phenoxybenzamine had no influence on the lipid mobilizing effect of adrenergic agonists. This effect was absent also when drugs with the strong alpha sympathomimetic effects, e.g. norepinephrine and noroxedrine, were used. 2) On the other hand, alpha adrenergic agonist phenylephrine was able to antagonize in rat adipose tissue the lipid mobilizing effect of beta adrenergic agonist isoproterenol. 3) From our experiments it can be concluded, that phenylephrine acts as a competitive dualist on beta adrenergic receptors, it reduces the effect of full agonist (e.g. isoproterenol) to the level of its own maximum lipolytic effect. No participation of alpha adrenergic receptors in described effects of phenylephrine were detected, because neither the lipolytic, nor the lipolysis blocking effects of phenylephrine were influenced by alpha adrenergic blocking agents. Our studies using alpha adrenergic agonist phenylephrine or nonselective alpha adrenergic blocking agents did not indicate the presence of any alpha adrenergically controlled lipolysis in the rat adipose tissue. However, the role of antilipolytic alpha 2 adrenoceptors in rat adipose tissue cannot be completely excluded, some of these receptors were found on the membranes of rat adipocytes. Our future study deals with this problem.

Adipose Tissue↗
PubMed1988

Plasma hormone levels in relation to lipid and protein metabolism during prolonged fasting in king penguin chicks.

Chicks of king penguin (Aptenodytes patagonica), while only 3-4 months old, tolerate 4-6 months of fasting when they are abandoned by their parents during the subantarctic winter. The body mass of nine chicks, which were followed during this natural winter fast, was 13.1 kg at capture and 3.4 kg after 150 days of fasting, a 74% decrease. The longer phase II (129 days) was marked by lipid mobilization and protein sparing, as indicated by a continuous increase in plasma levels of free fatty acids, glycerol, and beta-hydroxybutyrate, whereas plasma alanine, uric acid, and urea remained stable at low values. In phase III, by contrast, plasma concentrations of lipid-derived metabolites decreased, while plasma alanine, uric acid, and urea increased markedly, indicating an increase in protein utilization. Plasma insulin concentration did not significantly change during either phase II or phase III. Plasma glucagon remained constant during phase II and at the beginning of phase III but increased 2.6 times afterward. Plasma corticosterone increased only slightly during the first 4 months of the fast but reached very high values at the end of phase II and the beginning of phase III (4.7 times basal values); moreover, it further increased 3.1 times before phase III was stopped. Altogether, these data accord with the idea that the outstanding resistance of king penguin chicks to starvation is due to the ability to extensively prolong the situation of protein sparing, which seems to require the maintenance of low plasma concentrations of corticosterone and insulin for up to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Distribution, lateral mobility and function of membrane proteins incorporated into giant unilamellar vesicles.

GUVs have been widely used for studies on lipid mobility, membrane dynamics and lipid domain (raft) formation, using single molecule techniques like fluorescence correlation spectroscopy. Reports on membrane protein dynamics in these types of model membranes are by far less advanced due to the difficulty of incorporating proteins into GUVs in a functional state. We have used sucrose to prevent four distinct membrane protein(s) (complexes) from inactivating during the dehydration step of the GUV-formation process. The amount of sucrose was optimized such that the proteins retained 100% biological activity, and many proteo-GUVs were obtained. Although GUVs could be formed by hydration of lipid mixtures composed of neutral and anionic lipids, an alternate current electric field was required for GUV formation from neutral lipids. Distribution, lateral mobility, and function of an ATP-binding cassette transport system, an ion-linked transporter, and a mechanosensitive channel in GUVs were determined by confocal imaging, fluorescence correlation spectroscopy, patch-clamp measurements, and biochemical techniques. In addition, we show that sucrose slows down the lateral mobility of fluorescent lipid analogs, possibly due to hydrogen-bonding with the lipid headgroups, leading to larger complexes with reduced mobility.

ATP-Binding Cassette Transporters↗
PubMed1991

[Effect of tolbutamide on lipolytic processes in blood and fat tissue of rats maintained in normothermic and hypothermic conditions].

The effect of tolbutamide administered in vivo or added to the incubation medium on lipolysis in adipose tissue and in blood has been studied in rats. Tissue lipolysis was lowered by 118 to 156% in groups of rats receiving tolbutamide in vivo. The addition of tolbutamide directly to the incubation medium caused an increase in the lipid mobilizing activity, while the addition of insulin inhibited lipolysis in each case. The effect of tolbutamide administered in vivo may be indirect through an increase in insulin binding and/or the drug may influence directly the permeability of cell membrane for ions and glucose. An increase in the lipid mobilizing activity observed in experiments consisting in the addition of tolbutamide to the incubation medium may be linked to the low glucose level and greater demand for free fatty acids or to the low level of insulin in the incubation medium.

Adipose Tissue↗
PubMed1991

Anorectic effect of alpha 2-antagonists in dog: effect of acute and chronic treatment.

Acute oral administration of alpha 2-antagonists (yohimbine, RX 821002, atipamezole: 1 mg/kg each) reduced dog food intake. Yohimbine reduced food intake over 20 hours, while the effect of the two other drugs lasted only 2 hours. Yohimbine (0.4 or 1 microgram/kg) gave the same results. At these doses, it promoted a lasting durable increase in plasma nonesterified fatty acids and catecholamines levels and a transient elevation of plasma insulin levels. The beta-antagonist nadolol (4 mg/kg per os) suppressed the yohimbine-induced lipid mobilization without modifying its anorectic effect. Chronic oral yohimbine (0.4 mg/kg/day during 14 days) reduced food intake and promoted a weight loss. Normal food intake was recovered two days after yohimbine withdrawal. No change was observed in the number of platelet alpha 2-adrenergic receptors. In addition to their lipid mobilizing action and sympathetic tone stimulation, alpha 2-antagonist compounds reduce food intake.

Adrenergic alpha-Antagonists↗
PubMed2003

Interactions among contaminants and nutritional lipids during mobilization by digestive fluids of marine invertebrates.

Coastal sediments contain complex mixtures of hydrophobic compounds including organic contaminants such as polycyclic aromatic hydrocarbons and biogenic compounds such as cholesterol and phospholipids. Within the guts of benthic invertebrates, these mixtures are subjected to digestive, chemical conditions that can be rich in surfactants and proteinaceous material. Using in vitro incubations as proxy for digestive exposure, we studied the solubilization of binary mixtures of nutritional and contaminant lipids into artificial seawater and six marine invertebrate gut fluids (Molpadia intermedia, Cucumaria frondosa, Arenicola marina, Arenicola brasiliensis, Parastichopus californicus, and Nereis virens). For animals with surfactant micelles or high protein concentrations, solubilization interactions were frequent. For example, in Arenicola marina gut fluid, benzo(a)pyrene enhanced the solubilization of hexadecane (491% of the compound alone) and palmitic acid (130%) but hindered cholesterol (83%). Benzo(a)pyrene concentrations increased in gut fluids in the presence of cholesterol (137% of BaP alone), phenanthrene (154%), lecithin (140%), and hexadecanol (232%). In A. marina gut fluid, dilution with seawater indicated that these enhancements occur only when micelles are present. Sediment-water partitioning models, used to predict the bioavailability of hydrophobic organic chemicals, do not account for such interactions between solubilizates (compounds solubilized in micelles). However, for animals exposed via a digestive tract containing micelles or high protein concentrations, digestive bioavailability and perhaps bioaccumulation are likely influenced by these interactions.

Animals↗
PubMed1998

[Changes in intraoperative blood glucose and ketone body concentrations during the repair of lipomyelomeningocele in children].

Blood glucose and ketone body (3-hydroxy-butyrate) concentrations were measured in 8 children (4.2 +/- 2.8 years old) during the repair of lipomyelomeningocele (9.0 +/- 2.6 hours) to elucidate whether lipid mobilization can be prevented by glucose infusion at the rate of 0.2 +/- 0.05 g.kg-1.h-1. The operation was followed in about 4 hours by a significant increase in blood glucose and ketone body concentrations, with their maximum value of 195 +/- 75 mg.dl-1 and 656 +/- 75 mumol.l-1, respectively (P < 0.05), as compared with the preoperative level. The lipid mobilization soon returned to normal state by increasing the rate of glucose infusion, as indicated by ketone body level of 92 +/- 58 mumol.l-1 at the end of operation. These results show that glucose infusion rate should be adjusted based on serial analysis of both blood sugar and ketone body concentrations in the anesthetic management of children undergoing a long operation.

3-Hydroxybutyric Acid↗
PubMed1984

Effect of oestradiol on catecholamine-stimulated lipolysis.

The authors studied the effect of a single in vivo dose of oestradiol (OE) on adrenergic lipolysis in the epididymal adipose tissue of adult and juvenile male rats, and the effect of OE on plasma free fatty acids (FFA), cholesterol and beta-lipoprotein levels at various intervals after its administration. It was found that OE injected 24 h beforehand in vivo (s.c.), in doses of 100 and 200 micrograms X kg-1 body weight, significantly potentiated the lipid-mobilizing action of the catecholamines noradrenaline (NOR) and isoprenaline (ISO) in adult rats (the action of ISO was potentiated more intensively); in addition, the adipose tissue became more sensitive to the action of NOR, but not of ISO. Raising the dose of OE to 400 micrograms X kg-1 did not enhance the potentiation of the lipolytic action of the catecholamines any further; on the contrary, the lipid mobilizing effect of the catecholamines was potentiated less than after half this dose. Following the s.c. injection of an oily OE solution, the lipolytic effect was potentiated after more than 7 h; the potentiation was strongest after 12 h, but only as far as the maximum attainable degree of lipolysis was concerned. Potentiation of adrenergic lipolysis was found only in adult male rats. In male rats weighing 130-150 g the lipolytic effect of catecholamines (in mumol/g adipose tissue) was significantly greater than in adult animals and the pre-administration of OE did not potentiate adrenergic lipolysis any further. Determination of plasma FFA, cholesterol and beta-lipoprotein levels 1, 2, 4 and 6 hours after the s.c. injection of OE showed only nonsignificant changes (an increase in FFA and a decrease in cholesterol). The authors consider it important to distinguish between the effect of OE on catecholamine-stimulated lipolysis in depot adipose tissue and its effect on lipid metabolism. In their opinion, the dose-dependent effect of OE on muscular and metabolic adrenergic reactions could be one of the factors co-reversible for certain side reactions to steroid contraceptives.

Adipose Tissue↗