The mode of action of a lipid mobilising factor in cancer cachexia

Cachexia is characterised by a progressive weight loss due to depletion of both skeletal muscle and adipose tissue. The loss of adipose tissue is due to the production of a tumour-derived lipid mobilising factor (LMF), which has been shown to directly induce lipolysis in isolated epididymal murine white adipocytes. The administration of LMF to a non-tumour bearing mice produced a rapid weight loss, with a specific reduction in carcass lipid with also some redistribution of lipid with the accumulation of lipid in the liver. There was also up-regulation of uncoupling protein-1 and -2 mRNA and protein expression in brown adipose tissue, suggesting that an adaptive process occurs due to increased energy mobilisation. There was also up-regulation of UCP-2 in the livers of LMF treated mice, suggesting a protective mechanism to the build up of lipid in the livers, which would produce free radical by-products. LMF was also shown to stimulate cyclic AMP production in CHO-K1 cells transfected with human -3 adrenergic receptors and inhibited by the -β3 antagonist SR59230A. LMF binding was also inhibited by SR59230A in isolated receptors. This suggests that LMF mediates its effects through a β3 adrenergic receptor. There were also changes in glucose and fatty acid uptake in LMF treated mice, which suggests metabolic changes are occurring. The study suggests that a tumour derived lipolytic factor acts through the 3 adrenoceptor producing effects on lipid mobilisation, energy expenditure and glucose metabolism.

Hydrogenated Fat Intake during Pregnancy and Lactation Modifies Serum Lipid Profile and Adipokine mRNA in 21-day-old Rats

Objective We examined whether feeding pregnant and lactating rats hydrogenated fats rich in trans-fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 21-d-old offspring. Methods Pregnant and lactating Wistar rats were fed with a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). After delivery, male offspring were weighed weekly and killed at day 21 of life by decapitation. Blood and retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Results Offspring of T-group rats had increased serum triacylglycerols and cholesterol, white adipose tissue plasminogen activator inhibitor-1, and tumor necrosis factor-α gene expression, and carcass lipid content and decreased blood leptin and adiponectin and adiponectin gene expression. Conclusion Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation alters the blood lipid profiles and the expression of proinflammatory adipokynes by the adipose tissue of offspring aged 21 d.

Nutritional value of some small indigenous fish species (SIS) of Bangladesh

Twenty three small indigenous fish species (SIS) in the size range of 3-18 cm were analyzed for proximate composition and minerals (Ca and P) content to evaluate their nutritive value. The moisture content of different species ranged between 71.00 and 81.94%. In general, small sized fishes showed higher moisture content. The muscle protein content among the species varied widely (16.16-22.28%). In general, the muscle protein content of fishes showed higher value than the whole carcass protein content. The carcass lipid content varied between 1.87 and 9.55% and showed an inverse relationship with the moisture content. The gross energy content ranged from 19.51-27.30 KJ/g on dry matter basis. In the present study, the calcium and phosphorus contents ranged between 0.85-3.20% and 1.01-3.29% respectively. The calcium and phosphorus ratio (Ca/P) varied between 0.44 and 2.00. From the nutritional point of view, it shows that the SIS are good source of protein and minerals especially calcium and phosphorus

INFLUENCE OF DIETARY-PROTEIN INTAKE AND RECOMBINANT HUMAN SOMATOTROPIN ADMINISTRATION ON GROWTH AND BODY-COMPOSITION OF JUVENILE TAMBACU (A PIARACTUS-MESOPOTAMICUS X COLOSSOMA-MACROPOMUM CROSS)

This experiment was undertaken to study the interaction between level of dietary protein and recombinant human somatotropin (rhGH) administration on performance and body composition of juvenile tambacu (a crossbred Brazilian fish). A total of 72 juvenile tambacu, initially weighing and measuring (mean +/- s.e.m.) 23 +/- 2 g and 9 +/- 0.5 cm, respectively, were randomly divided into 18 groups of 4 fish each. Water temperature was 28 degrees C. Triplicate groups received one of two levels of dietary protein (15 and 30% as fed basis) and one of 3 doses of rhGH (0, 2 and 4 mu g/g) via intraperitoneal injection twice a week for 6 weeks, using a randomized complete block design. Somatotropin was noted to stimulate linear and body weight gain. The higher protein level supported increased growth in weight and length, but there was no interaction between protein level and rhGH dose for either parameter. Protein efficiency ratio and percentage protein deposited showed higher values on diets containing 15% protein. Somatotropin treatment did not significantly affect body composition, but there was a trend towards improved protein retention and reduced carcass lipid. In conclusion, the results of this experiment suggest that rhGH is able to stimulate linear gain in tambacu.

Metabolic adaptations induced by long-term fasting in quails

After up to 21 days without food, adult male quails (Coturnix coturnix japonica) lost about 45% of the initial body weight (100-150 g). As in naturally fast-adapted and larger birds, three phases were identified during prolonged fasting in quails. Phase I lasted 2-3 days and was characterized by a rapid decrease in the rate of body weight loss and high fat mobilization. Phase II was longer and characterized by a slow and steady decline in the rates of body weight loss and of nitrogen excretion. The third (critical) period was marked by an abrupt increase in the rates of body weight loss and of nitrogen excretion. Despite their small size, the duration of phase II in quails was relatively long, a clear advantage for the study of the relationships between the several metabolic events that occur during this crucial adaptative period. Also, the beginning of phase III could be precisely determined. Changes in blood glucose, plasma FFA and triacylglycerols levels, as well as in liver and carcass lipid content were similar to those found in other species of birds. Therefore, quails seem to be a suitable model to investigate the biochemical mechanisms involved in the metabolic adjustments to prolonged food deprivation in non fasting-adapted birds. © 1995.

Composição corporal e índices biométricos do pacu, Piaractus mesopotamicus Holmberg, 1887 (Osteichthyes, Characidae) submetido a ciclos alternados de restrição alimentar e realimentação

The present paper evaluated, through hepatosomatic/mesenteric fat indexes and body composition, the pacu energy utilization when submitted to alternated food restriction/refeeding cycles during the growout period. Juveniles were distributed in three pounds and submitted to different feeding programs: A (ad libitum daily feeding), B (4-week feeding restriction and 9-week refeeding) and C (6-week feeding restrictions and 7-week refeeding), totaling 13 weeks for each cycle (4 experimental cycles). At the end of the periods, fish were sampled to obtain biometrics and biochemical data. The results showed that, during the first two cycles, C treatment obtained the best compensatory growth. Carcass lipid and water contents were inversely related, with body fat decrease. Fishes under B and C treatment during food restriction utilized liver and mesentery energy stores. These parameters were re-established in the refeeding phase, in all cycles.

Respostas metabólicas, morfologia do tecido muscular e expressão dos genes relacionados ao crescimento e à atrofia muscular durante o jejum e realimentação em juvenis de tilápia-do-Nilo

Pós-graduação em Zootecnia - FCAV

Green tea extract rich in epigallocatechin-3-gallate prevents fatty liver by ampk activation via lkb1 in mice fed a high-fat diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tumor-host interactions

A number of malignant tumors interact with the host to cause a syndrome of cachexia, characterized by extensive loss of adipose tissue and skeletal muscle mass, but with preservation of proteins in visceral tissues. Although anorexia is frequently present, the body composition changes in cancer cachexia cannot be explained by nutritional deprivation alone. Loss of skeletal muscle mass is a result of depression in protein synthesis and an increase in protein degradation. The main degradative pathway that has been found to have increased expression and activity in the skeletal muscle of cachectic patients is the ubiquitin-proteasome proteolytic pathway. Cachexia-inducing tumors produce catabolic factors such as proteolysis-inducing factor (PIF), a 24 kDa sulfated glycoprotein, which inhibit protein synthesis and stimulate degradation of intracellular proteins in skeletal muscle by inducing an increased expression of regulatory components of the ubiquitin-proteasome proteolytic pathway. While the oligosaccharide chains in PIF are required to initiate protein degradation the central polypeptide core may act as a growth and survival factor. Only cachexia-inducing tumors are capable of elaborating fully glycosylated PIF, and the selectivity of production possibly rests with the acquisition of the necessary glycosylating enzymes, rather than expressing the gene for the polypeptide core. Loss of adipose tissue is probably the result of an increase in catabolism rather than a defect in anabolism. A lipid mobilizing factor (LMF), identical with the plasma protein Zn-α2-glycoprotein (ZAG) is found in the urine of cachectic cancer patients and is produced by tumors causing a decrease in carcass lipid. LMF causes triglyceride hydrolysis in adipose tissue through a cyclic AMP-mediated process by interaction with a β3-adrenoreceptor. Thus, by producing circulating factors certain malignant tumors are able to interfere with host metabolism even without metastasis to that particular site. © 2004 Wiley-Liss, Inc.

Second messenger pathways in the action of cachectic factors

Cachexia in cancer is characterised by progressive depletion of both adipose tissue stores and skeletal muscle mass. Two catabolic factors produced by cachexia-inducing tumours have the potential for inducing these changes in body composition: (i) proteolysis-inducing factor (PIF) which acts on skeletal muscle to induce both protein degradation and inhibit protein synthesis, (ii) lipid-mobilising factor (LMF), which has been shown to directly induce lipolysis in isolated epididymal murine white adipocytes. Administration of lipid-mobilising factor (LMF) to mice produced a specific reduction in carcass lipid with a tendency to increase non-fat carcass mass. Treatment of murine myoblasts, myotubes and tumour cells with tumour-produced LMF, caused concentration dependent stimulation of protein synthesis, within a 24hr period. It produced an increase in intracellular cyclic AMP levels, which was linearly related to the increase in protein synthesis. The observed effect was attenuated by pretreating cells with the adenylate cyclase inhibitor, MDL12330A and was additive with stimulation produced by forskolin. Both propranolol and a specific 3 adrenergic antagonist SR59230A, significantly reduced the stimulation of protein synthesis induced by LMF. LMF also affected protein degradation in vitro, as demonstrated by a reduction in proteasome activity, a key component of the ubiquitin-dependent proteolytic pathway. These effects were opposite to those produced by PIF which caused both a decrease in the rate of protein synthesis and an elevation on protein breakdown when incubated in vitro.Incubation of LMF with a fat cell line produced alterations in the levels of guanine-nucleotide binding proteins (G proteins). This was also evident in adipocyte plasma membranes isolated from mice bearing the tumour model of cachexia, MAC16 adenocarcinoma and from patients with cancer cachexia. Progression through the cachectic state induced an upregulation of stimulatory G proteins paralleled with a downregulation of inhibitory G proteins. These changes would contribute to the increased lipid mobilisation seen in cancer cachexia.

A Palatable Hyperlipidic Diet Causes Obesity and Affects Brain Glucose Metabolism in Rats

Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

Exercise Training in Rats Impairs the Replenishment of White Adipose Tissue after Partial Lipectomy

The aim of this study was to evaluate the effect of exercise training on the metabolism of rats following the partial removal of fat pads. Three-month-old male Wistar rats were subjected to the partial removal (L) of retroperitoneal white adipose tissue (RET) and epididymal white adipose tissue (EPI), or a sham operation (Sh). Seven days after surgery, both sets of rats were subdivided into exercised (LE or ShE) (swimming 90 min/day, 5 days/week, 6 weeks) and sedentary (LS or ShS) groups. Partial removal of the fat pads increased the lipogenesis rates in both the RET and EPI and decreased the weight and lypolysis rate of the EPI, while the RET weight was not significantly affected by lipectomy. In both lipectomized and sham-operated groups, exercise training caused a reduction in carcass lipid content, food intake, RET and EPI weights, and RET lipogenesis rate. On the other hand, the exercise training increased the percentage of diet-derived lipid accumulation in both tissues, either in sham and lipectomized rats. These results confirmed that regrowth is not uniform and depends on the particular fat pad that is excised. They also demonstrated that exercise training following the partial removal of fat pads modified adipose tissue metabolism, impaired the replenishment of adipose tissue, and decrease body adiposity.

Effect of protein, carbohydrate, lipid, and selenium levels on the performance, carcass yield, and blood changes in broilers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comparative study on the effect of dietary lipid level on growth and feed utilization for gibel carp (Carassius auratus gibelio) and Chinese longsnout catfish (Leiocassis longirostris Gunther)

An 8-week growth trial investigated the effect of dietary lipid level on growth performance of a carnivorous fish, Chinese longsnout catfish (Leiocassis longirostris Gunther) and an omnivorous fish, gibel carp (Carassius auratus gibelio). For each species, seven isonitrogenous semi-purified diets (455 g kg(-1) crude protein for Chinese longsnout catfish and 385 g kg(-1) crude protein for gibel carp) were formulated to contain 30, 60, 90, 120, 150, 180 or 210 g kg(-1) lipid. For Chinese longsnout catfish, feed intake (FI) decreased with increasing dietary lipid and there was no significant difference in feed intake from 90 to 210 g kg(-1) lipid. Specific growth rate (SGR) increased with dietary lipid level (P < 0.05) and the 150 and 180 g kg(-1) groups were the best. Feed conversion efficiency (FCE), protein retention efficiency (PRE) and energy retention efficiency (ERE) were higher at 180 g kg(-1) lipid. For gibel carp, FI decreased with increased dietary lipid and 180 and 210 g kg(-1) lipid groups showed lower values. SGR increased with dietary lipid level and the 150 and 180 g kg(-1) were the best. FCE was higher at 180 g kg(-1) lipid level. PRE increased with dietary lipid level and there was no significant difference in groups from 120 to 210 g kg(-1) dietary lipid. ERE increased with increasing dietary lipid level, and groups fed 120, 150 and 180 g kg(-1) lipid showed the highest values. In Chinese longsnout catfish, increase in dietary lipid level, resulted in increased carcass dry matter, crude protein, crude lipid and gross energy. In gibel carp, dry matter, crude protein, and crude lipid increased with dietary lipid level. Based on regression between SGR and dietary lipid, dietary lipid requirements for Chinese longsnout catfish and gibel carp were 142.6 and 140.5 g kg(-1), respectively.