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Fatty acid breakdown in developing embryos of Brassica napus L.

Developing Brassica napus embryos are primarily concerned with the accumulation of storage products, namely oil, starch and protein. The presence of fatty acid catabolic pathways in the background of this biosynthetic activity was investigated. Enzymes involved in the process of lipid mobilization, such as malate synthase and isocitrate lyase, are detectable towards the late stages of embryo development. [(14)C]Acetate feeding experiments also reveal that fatty acid catabolism becomes increasingly functional as the embryo matures.

Acetates↗

[Molecular and cellular biological analysis on cancer cachexia syndrome].

About half of patients with cancer will suffer from wasting syndrome, called cancer cachexia, which shows abnormality of homeostasis, nutrition, endocrine function, metabolism, immunity et al. This syndrome is characterized with anorexia and weight loss caused by degradation of skeletal muscle and adipose tissue. Progressive weight loss is responsible not only for a poor quality of life and poor response to anti-cancer drug, but also shorter survival time comparing patient without weight loss. Various factors have been found as mediators of this syndrome base on the development of immunology, biochemistry and molecular and cellular biology. These include several cytokines, proteolysis-inducing factor (PIF), lipid-mobilizing factor (LMF), apoptosis-inducing factor and another factors. Recentry, molecular biological analysis makes clear more detail mechanisms of cancer cachexia syndrome, for example, ubiqutin/proteasome pathway, activation of nuclear transcriptional factors and others. These progresses will contribute not only to establish new treatment but also to carry out "order-made palliative oncology" using DNA-chip and/or Protein-chip in near future.

Animals↗

Temporal relationships between dietary, plasma, hepatic, and adipose tissue lipids after short-term feeding of safflower oil to rats.

The objectives of this research were to study effects of dietary neutral fat on the concentration and the fatty acid composition of triglyceride (TG) and other lipid classes in plasma, liver, and adipose tissue and, particularly, to study the temporal and precursor-product relationship among those various lipid pools. Accordingly, male rats were administered 1.5 ml. of safflower oil by gastric intubation at 0, 4, and 8 hours after a 16-hour fast. Samples of plasma, liver, and adipose tissue were collected from groups of rats before fat feeding (0 time, controls), during the period of feeding (4 and 8 hours), and at several times thereafter up to 36 hours (28 hours after the last meal). The esterified lipids in all lipid fractions of liver and plasma became enriched with linoleic acid (18:2) during the experiment. The enrichment of plasma and hepatic TG, and of plasma FFA with 18:2 was substantial, reaching a maximum 8 hours after the third meal, whereas only a modest enrichment of adipose tissue TG was observed. The enrichment with 18:2 of various lipid fractions proceeded in the following sequence: total plasma TG became enriched first with 18:2 of chylomicron TG fatty acids during the period of active absorption of fat. Second, plasma FFA were enriched with 18:2 derived presumably from metabolism of chylomicron TG. Subsequently, enrichment of hepatic TG with 18:2 was observed. After maximum enrichment was attained, the percentage of 18:2 in these various lipid pools decreased in the following order. The percentage of 18:2 in plasma FFA fell rapidly, followed by a slower decrease of the 18:2 content of plasma TG and, finally, by an even slower decline of the 18:2 content of hepatic TG. All lipid fractions except plasma FFA contained an increased content of 18:2 even 28 hours following the last fattly meal. It can be deduced from these temporal relationships that plasma TG is derived indirectly from dietary TG long after active absorption of dietary fat has ceased. The composition of hepatic TG is altered by dietary neutral fat, through the intermediary uptake of plasma FFA derived from metabolism of chylomicron TG; this hepatic TG, which reflects dietary fat, is a significant precursor pool of the plasma TG in the postabsorptive state.

Adipose Tissue↗

Metabolic control in diabetic pregnancy. Variations in plasma concentrations of glucose, free fatty acids, glycerol, ketone bodies, insulin, and human chorionic somatomammotropin during the last trimester.

Metabolic control was evaluated under standard conditions in pregnant gestational and insulin-dependent diabetic patients and control subjects from: (1) changes during an 8 hour period in blood glucose, free fatty acids (FFA), glycerol, ketone bodies, chorionic somatomammotropin (HCS), and insulin during the last trimester and (2) changes from weeks 32 to 40 in fasting blood glucose, FFA, glycerol, and ketone bodies. Mean glucose levels calculated from five daily analysis 28 days before delivery were determined in insulin-dependent and gestational diabetic patients (pregnancy glucose level). Group mean 8 hour glucose levels were similar in diabetic patients and control subjects, but glucose swings were greater in diabetic patients. Gestational diabetic patients had delayed insulin response following meals. FFA, glycerol, and ketone bodies varied in parallel with a simmilar pattern in diabetic patients and control subjects. Insulin-dependent diabetic patients had suppressed lipid mobilization in the afternoon when glucose levels were almost normal. In control subjects, FFA, glycerol, and ketone bodies were not above normal nonpregnant values. Diabetic patients showed great individual variations in all parameters measured. FFA and ketone bodies were significantly above normal; glycerol and glucose were normal. Pregnancy glucose levels were significantly correlated to a mean amplitude of glycemic swings (MAGE) determined from the 8 hour glucose profiles. The glucose value 2 hours after breakfast correlated best to the MAGE value.

Adult↗

Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management.

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.

Adrenergic beta-Antagonists↗

MR imaging and MR spectroscopy in rhizomelic chondrodysplasia punctata.

A case of rhizomelic chondrodysplasia punctata was investigated with MR imaging of the brain and hydrogen-1 MR spectroscopy of the brain and blood. Areas with abnormal signal hyperintensity on T2-weighted images or hypointensity on T1-weighted images were detected in the subcortical white matter. MR spectroscopy of the brain showed that normal-appearing white matter was characterized by increased levels of mobile lipids and myo-inositol, reduced levels of choline, and the presence of acetate. The importance of these metabolic anomalies is correlated to the deficiency in plasmalogen biosynthesis.

Acyltransferases↗

The alpha 2-adrenergic receptor gene and body fat content and distribution: the HERITAGE Family Study.

BACKGROUND: Among adrenergic receptor subtypes that regulate lipid mobilization, the alpha2-adrenergic receptor is involved in the inhibition of fatty acid mobilization from adipose tissue. A C-1291G polymorphism is located in the alpha2-adrenergic receptor gene (ADRA2A) but no association with body fat accumulation has been reported yet. MATERIALS AND METHODS: Body mass index (BMI), fat mass (FAT), percentage body fat (%FAT), trunk-to-extremity skinfold ratio (TER), sum of eight skinfolds (SF8), and abdominal subcutaneous (ASF), visceral (AVF), and total (ATF) fat areas assessed by CT scan have been measured in adult sedentary white (n = 503) and black (n = 276) subjects participating in the HERITAGE Family Study. Association between the C-1291G polymorphism and each phenotype was tested separately in men and women of each race using ANCOVA with the effects of age as covariate in addition to the effects of BMI for TER and of FAT for AVF, ASF, and ATF. RESULTS: The allele frequencies of the ADRA2A C-1291G polymorphism differed between races. No association was observed in white subjects, except for a moderate effect of the polymorphism accounting for less than 1% of the variance in AVF and ATF in women. In black subjects, however, the G-1291 allele was found to be associated with an increase of TER in men (3.8% of variance accounted for by the polymorphism), while in black women it was associated with a decrease in TER (2.9%) and in AVF (2.5%). CONCLUSION: These results suggest a role for the ADRA2A gene in determining the propensity to store fat in the abdominal area, independently of total body fatness.

Adult↗

Effect of triiodothyronine on blood lipids in obesity.

Different blood lipid components were evaluated in obese and normal Egyptians. In obese, plasma levels of total lipoproteins, beta-lipoprotein, total cholesterol, triglycerides, and non-esterified fatty acids were found to be significantly elevated. The plasma levels of esterified cholesterol and phospholipids were found to be significantly reduced. Tertroxine caused a drop of the plasma level of total lipoproteins, beta lipoproteins and total cholesterol and rise of plasma level of non-esterified fatty acids.

Adult↗

Influence of testosterone on blood sugar, serum insulin and free fatty acid responses to glucose in normal male dog.

The influence of testosterone propionate chronic treatment on blood sugar, serum immunoreactive insulin and free fatty acid levels of male, normal, fasted, unanesthetized dogs, basally and during an intravenous glucose tolerance test has been studied. Control experiments using uninjected or vehicle-injected dogs were also performed. Blood sugar and serum immunoreactive insulin basal levels were not affected by testosterone propionate and/or its vehicle, but serum free fatty acids basal values were increased. The blood sugar curve during the test observed in the dogs in the three conditions differed little; neither glucose space nor glucose "k" value were affected by treatments. Testosterone administration reduced by 50% the serum immunoreactive insulin peak following glucose load, as compared to vehicle-injected controls. Hyperglycemia and hyperinsulinaemia induced a fall in serum free fatty acid levels in control groups, followed by a recovery period at the end of the test. Either the fall or the recovery were more intense in testosterone-treated dogs than in vehicle-injected controls. Results are discussed, emphasizing that testosterone exerts a moderate "diabetogenic" action in male dog, inasmuch as although it intensely promotes lipid mobilization and moderately reduces the insulin response to glucose, fails to induce any glucose intolerance.

Animals↗

[Age-dependence of catecholamine effects in man. IV. Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics].

In order to characterize age differences in the lipolytic effect of catecholamines on tests of subcutaneous adipose tissue of test persons aged from 0.1 to 10 years, from 20 to 40 years, and from 60 to 75 years the influence of propranolol, phentolamine and theophyllin on the release of glycerol by isoprenalin and adrenalin was investigated. Propranolol (10(8) and 10(5) mol/1) inhibits the lipolysis in the adipose tissue of all age groups stimulated by isoprenalin (10(6)and 10(5) mol/1). The following Ki-values were calculated: 2x10(6) mol/1in the tissue of adults, 0.5 x 10(6) mol/1 in the infantile adipose tissue, 0.2 X 10(6) mol/1 in the tissue of old persons. Phentolamine (10(5) mol/1) increases the lipolytic effect of adrenalin (10(5) mol/1), there are no age differences. Theophyllin (10 (2) mol/1) increases the release of glycerol induced by isoprenalin (10(5) mol/1) in infantile and adult adipose tissue, however, it has no influence on them in the adipose tissue of old man. The findings suggest the higher sensitivity of the fat cells of the ageing organism to beta-adrenergics underlies a higher affinity of the adrenergics to the specific beta-adrenoceptors in the cytoplasm membrane of the adipocytes. The more intensive lipid mobilization in old age by beta-adrenergics is explained by a low activity of the cAMP-phosphodiesterase of the fat cells and by the higher and possibly longer lasting increase of intracellular cAMP in this age group.

Adipose Tissue↗

Localized and transient changes in plasma membrane fluidity during in vitro myoblast fusion: an 1H-NMR study.

High resolution proton NMR was used to study the cell surface molecular events which take place during in vitro myoblast differentiation and fusion. The CH3 and (CH2)n spectral signals were followed throughout in vitro myogenic development. The results show that although both the T1 and T2 relaxation times of the CH3 and (CH2)n groups are sensitive to the fusion process, T1 is the most sensitive. Both T1 of CH3 and (CH2)n increased before fusion indicating a higher degree of molecular motion and then returned to their original values. These results demonstrate how mobile lipid domains observed with proton NMR can be used to study the changes taking place during myoblast differentiation, particularly myoblast membrane fusion.

Animals↗

Pathogenesis of cancer cachexia.

Cachexia is a progressive wasting syndrome characterized by extensive loss of adipose tissue and skeletal muscle. It occurs in about half of all cancer patients. While anorexia also may be present, the energy deficit alone does not explain the pathogenesis of cachexia. The presence of an acute phase response (APR) has been linked to accelerated weight loss and a shortened survival time. The APR is thought to be initiated by cytokines such as interleukin (IL)-6 and IL-8, production of which is induced by a tumor factor, proteolysis inducing factor (PIF). Cachectic cancer patients also show an increased expression of uncoupling protein-3 in muscle, which may act as an energy sink, increasing energy expenditure. Loss of adipose tissue appears to be due to an increase in degradation of triglycerides, rather than a decrease in synthesis. One candidate for this effect is a tumor lipid mobilizing factor, which stimulates lipolysis directly through a cyclic AMP-mediated process via interaction with a beta3-adrenergic receptor. Loss of skeletal muscle arises from both a depression in protein synthesis and an increase in protein degradation. The major proteolytic pathway involved in intracellular protein breakdown in cachectic muscle is the ATP-ubiquitin-dependent proteolytic pathway. Both PIF and tumor necrosis factor-alpha, but not other cytokines, can induce expression of the key regulatory components of this pathway. Eicosapentaenoic acid, found in oily fish, effectively attenuates protein degradation in cachectic muscle by inhibiting the increased proteasome expression and can stabilize body weight in cachectic cancer patients.

Adipose Tissue↗

[Recent development in research and management of cancer anorexia-cachexia syndrome].

Cachexia is among the most debilitating and life-threatening aspects of cancer, and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be done by persistent inhibition of feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide-all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. Communication among physicians and other health care professionals provides the patient with a multidisciplinary approach to care. The patient record will be an excellent resource to document a plan of care and patient responses to treatment. Psychological distress and psychiatric disorders are common among cancer patients. These problems are also as common among the family members of people with cancer. The use of psychological and behavioral interventions in cancer is increasing, and recent studies have suggested that some of these techniques may affect quality of life and, perhaps, survival rates. Evaluations of relaxation, hypnosis, and short-term group psychotherapy have suggested some benefit with regard to anorexia and fatigue, although the population most likely to benefit from these interventions has not yet been determined. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.

Animals↗

(99m)Tc-HmPAO single photon emission tomography, magnetic resonance proton spectroscopy and neuropsychological testing in evaluation of carbon monoxide neurotoxicity.

There were 10 acutely CO poisoned study patients without CNS history (head traumas, epilepsy, dementia, migraine or alcoholic diseases) in whom (99m)Tc-HmPAO SPET, HMRS and neuropsychological testing were performed. 99mTc-HmPAO SPET and neuropsychological testing were performed twice: in acute phase and at six months post CO exposure. HMRS was carried out at 8 months post CO exposure. A multidimensional analysis of variance (MANOVA) was used to statistical analysis. Regional CBF disturbances in acute phase of CO poisoning were observed in frontal cortex, basal ganglia and parietal cortex respectively. The most reversible, as seen in control (99m)Tc-HmPAO SPET examination, were the changes observed in parietal cortex. Diffuse generalized cortex hypoperfusion, both in acute phase and at 6 months post exposure, was seen only in one the patient. In all of the examined patients different elevation in mobile lipid or/and lactate concentration in frontal lobe or/and basal ganglia was revealed by HMRS evaluation at eight months post acute CO exposure. Results of neuropsychological testing at baseline and at 6 months partially correlated with neuro-imagine techniques applied.

Acute Disease↗

1H-NMR evidence for a different response to the same dose (2 Gy) of ionizing radiation of MG-63 human osteosarcoma cells and three-dimensional spheroids.

High resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to examine the response of the MG-63 osteosarcoma cell line grown in monolayer and as 3-dimensional tumor spheroids to the same low dose (2 Gy) of ionizing radiation. The MG-63 cells and spheroids were irradiated at 24 h of growth and the 1H-NMR spectra of whole control and irradiated monolayer cells and of whole control and irradiated multicellular spheroids collected after another 24 h were compared. The 1H-NMR spectra of the perchloric acid extracts as well as the 2-dimensional 1H-NMR spectra of both pairs of cell systems were also obtained. Possible radiation-induced cell damage was determined by lactate dehydrogenase (LDH) release and variations in cell growth, while cell death was evaluated by chromatin dye Hoechst staining and DNA fragmentation assays. The results demonstrated that no cell damage took place, but that significant variations in numerous metabolites occured in both the monolayer cells and the spheroids after irradiation. Most of the changes observed were very similar in nature. In fact, significant increases in lactate, alanine, creatine and phosphocreatine and choline-containing metabolites and a significant decrease in glutathione (GSH) were observed in both cells and spheroids. However, while significant increases in CH2 and CH3 mobile lipids, glutamine/glutamate, taurine and inositol were seen in the spheroids, no variations in CH2 or CH3 lipids, glutamine/glutamate or taurine were recorded in the MG-63 cells grown in monolayer after irradiation. In addition, a significant decrease rather than a significant increase in inositol was also noted in the monolayer cells. The data presented seem to suggest that, although neither monolayer cells nor spheroids show apparent signs of damage after exposure to the same dose of ionizing radiation, very different cell death responses as well as very diverse antioxidant/osmoregulatory reactions were triggered by this stressing agent.

Bone Neoplasms↗

Wasting in gastrointestinal tract cancers: clinical and etiologic aspects.

One of the major complications found in patients affected by malignancy of the gastrointestinal tract is represented by an alteration of nutritional status, up to real cachexia. The factors responsible for the severe nutritional deficiencies are: metabolic alterations, which involve carbohydrate, lipid and protein metabolism; the reduced availability of nutritional substrates, due to neoplastic growth that, by expanding locally or destroying the affected organ, determines alterations of deglutition, digestion and food absorption; the effects of surgical therapy, radiotherapy and chemotherapy, which are able to cause temporary or permanent nutritional deficiencies; the effects of immunological mediators, and above all of tumor necrosis factor-alpha (TNF-alpha). In fact, TNF-alpha is considered the main mediator of cancer cachexia as it is responsible for different metabolic alterations, both directly and by the activation of other mediators, such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). In addition, a negative energy balance in cancer patients could occur as a consequence of increased energy requirements. In this connection, patients with different neoplasia localisation, show high or within the normal range energy expenditure values. These data indicate that the increase in energy metabolism is not likely to represent the main determining factor in neoplastic cachexia. In conclusion, since patients affected by malignancy of the gastrointestinal tract showed a reduction in body weight, fat and fat-free mass, accurate evaluation of nutritional status should be useful in the management and follow-up of these patients.

Journal Article↗

[Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].

The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.

Apolipoprotein A-I↗