Biomedical subjects

V E Baracos

Publications and source records attributed to V E Baracos.

At least 55 records · Page 3Linked to original sources

PubMed1993

Dietary lipids influence insulin action.

Insulin binding and insulin responsiveness are altered by dietary fat-induced changes in the fatty acid composition of the adipocyte plasma membrane. Feeding a high P/S diet increased polyunsaturated fatty acid content of major membrane phospholipids of adipocyte plasma membrane in normal and diabetic animals, increased membrane linoleic acid content, and prevented a decrease in arachidonic acid level in diabetic animals. The high P/S diet increased insulin binding in control animals. Animals fed the high P/S diet had significantly higher rates of insulin-stimulated glucose transport and lipogenesis than did animals fed the low P/S diet. Feeding a high P/S diet significantly increased the amount of glucose transported when expressed as a function of the specific amount of insulin bound. To determine if dietary fat-induced alterations in the fatty acid composition of skeletal muscle lipid alter insulin-dependent and basal muscle metabolism, contralateral epitrochlearis and extensor digitorum longus muscles were isolated and incubated in vitro. High levels of dietary omega-3 fatty acids reduced PGE2 and PGF2 alpha synthesis in extensor digitorum longus and epitrochlearis muscle. Insulin increased glucose and amino acid transport; the increase in glucose transport by insulin was significantly greater after consumption of the high omega-3 fatty acid diet. Rats fed high levels of omega-3 fatty acids showed reduced net protein degradation in the presence and absence of insulin due to decreased rates of protein degradation and synthesis. These experiments indicate that high levels of dietary omega-3 fatty acids alter muscle membrane composition, glucose transport, and metabolism of muscle protein. To determine if dietary fatty acids alter the onset of diabetes and insulin binding to liver nuclei in spontaneously diabetic rats, weanling rats were fed chow or semipurified diets containing 20% (w/w) fat of either high or low P/S ratio. Feeding a high P/S diet increased insulin binding to liver nuclei of control and diabetic animals. Although diet did not alter the onset of diabetes, insulin binding to liver nuclei is higher in animals at the onset of diabetes than in highly diabetic animals. Eight-week-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low P/S ratio to investigate the effect of diet on specific binding of insulin to liver nuclei. Insulin binding was highest in nuclei from lean mice fed a high P/S diet. Specific binding of insulin to nuclei from obese mice was also increased by the high P/S diet, but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1993

The effect of a cold environment on protein and energy metabolism in calves.

Eleven Holstein bull calves 35 d of age were assigned to one of three treatment groups: (1) W72, warm environment (20 degrees), 72 g feed/kg body weight (BW)0.75 per d, (2) C72, cold environment (-5 degrees), 72 g feed/kg BW0.75 per d, or (3) C90, cold environment (-5 degrees), 90 g feed/kg BW0.75 per d. Fractional synthesis rates (FSR) of protein in the rumen wall, rumen papillae, omasum, duodenum, kidney, liver, heart, longissimus dorsi, biceps femoris and skin were determined following a continuous infusion of [3H]phenylalanine. Phenylalanine flux was elevated in both groups of cold-adapted calves. FSR of protein in the two muscles and skin were reduced along with N retention in the calves in the C72 group compared with the other two groups. Muscle protein degradation, estimated from urinary N tau-methylhistidine excretion, tended to be elevated in both groups of cold-adapted calves. Reduced protein synthesis and increased protein degradation in the C72 group contributed to reduced muscle protein gain. It appears that when feed intake is limited in cold-adapted animals, muscle and skin have a lower priority for nutrients than other organs and tissues, resulting in reduced protein synthesis. It seems unlikely that thermogenesis due to enhanced protein synthesis contributed to the increased heat production in the cold.

Adaptation, Physiological↗

PubMed1992

Dietary omega 3 fatty acid alters prostaglandin synthesis, glucose transport and protein turnover in skeletal muscle of healthy and diabetic rats.

The present study was designed to determine if dietary-fat-induced alterations in the fatty acid composition of skeletal-muscle lipid alters insulin-dependent and basal muscle metabolism, including glucose and amino acid transport, prostaglandin (PG) synthesis and protein turnover. Rats were fed on high-fat semi-purified diets providing 19% or 1% omega 3 fatty acids in the form of fish oil, for 6 weeks. After 3 weeks, half of the rats were made diabetic by a single injection of streptozotocin (50 mg/kg body wt.). After a further 3 weeks, contralateral epitrochlearis and extensor digitorum longus (EDL) muscles from each rat were incubated in vitro. High levels of dietary omega 3 fatty acids decreased PGE2 and PGF2 alpha synthesis in EDL and epitrochlearis muscle (P less than 0.0001). Diabetes and insulin had no effect on PG synthesis. Diet did not alter basal glucose or amino acid transport in EDL muscle from healthy or diabetic rats. Insulin increased glucose and amino acid transport (P less than 0.0001); the increase in glucose transport by insulin was significantly greater in muscles of rats fed on high levels of omega 3 fatty acids (P less than 0.05). Epitrochlearis from rats fed on high levels of omega 3 fatty acids showed decreased net protein degradation in the presence and absence of insulin, owing to decreased rates of protein degradation and synthesis. The data suggest that high levels of dietary omega 3 fatty acids that alter muscle membrane composition also result in alterations in glucose transport and the metabolism of muscle protein.

Amino Acids↗

PubMed1992

Catch-up growth following Escherichia coli infection in weanling rats.

Infection is detrimental to growth, making it a serious problem for both humans and animals. To explore factors responsible for the restoration of tissue protein stores following infection, we developed a model of Escherichia coli infection suitable for studies of protein metabolism in growing animals. Weanling female Sprague-Dawley rats were given a single intraperitoneal injection of E coli (approximately 10(9) colony forming units [CFU]/kg body weight); control rats were injected with vehicle alone. Two days later, infected rats had lower (P less than .05) body weight (-11%), food intake (-49%), daily nitrogen balance (-64%), and lower protein mass of gastrocnemius muscle (-21%), tibialis anterior muscle (-23%), gastrointestinal tract (-15%), skin (-16%), and carcass (14%), compared with control rats. There was complete catch-up in terms of body weight, cumulative nitrogen balance, and carcass and tissue protein masses within 3 weeks of infection. Catch-up was achieved predominantly by increasing (P less than .05) the apparent nitrogen digestibility of the diet, thereby increasing the amount of nitrogen available to the body. Food intake did not increase and urinary nitrogen did not decrease during catch-up growth. E coli peritonitis in weanling rats provides a simple and useful model for the study of the effects of infection on growth and protein metabolism in growing animals.

Analysis of Variance↗

PubMed1992

Northern and in situ hybridization analyses of the effects of somatotropin on bovine mammary gene expression.

We investigated the potential roles of insulin-like growth factor-I and epidermal growth factor, both multifunctional regulators of mammary physiology, in somatotropin-stimulated lactation of dairy cattle. One insulin-like growth factor-I mRNA (7.4 kb) was detected in lactating mammary tissue; however, it became undetectable after somatotropin administration. Four type I insulin-like growth factor receptor mRNA (11.3, 6.2, 4.9, and 3.3 kb) were detected in mammary tissue and primarily expressed in alveolar epithelial cells. All of these receptor mRNA markedly decreased in mammary tissue from somatotropin-treated animals, although the cellular distribution pattern of receptor gene expression did not change. One epidermal growth factor receptor mRNA (10.5 kb) was present in mammary tissue and predominantly expressed in alveolar epithelial cells. Epidermal growth factor receptor mRNA decreased after somatotropin administration. The results from this study are consistent with the idea that the stimulatory effect of somatotropin during lactation is in part due to its ability to regulate the expression of specific genes or the stability of their mRNA in mammary tissue. The data also suggest roles for insulin-like growth factor-I and epidermal growth factor, as well as their homologous receptors, in controlling cellular changes in the mammary gland during somatotropin-stimulated lactation.

Animals↗

PubMed1991

Glutamine metabolism in skeletal muscles from the broiler chick (Gallus domesticus) and the laboratory rat (Rattus norvegicus)

Oxidative decarboxylation of L-[1-14C]glutamine was studied in isolated chick and rat skeletal muscles incubated in the presence of glucose, insulin and plasma concentrations of amino acids. (1) The rate of oxidative decarboxylation of L-[1-14C]glutamine was high, and exceeded that of L-[1-14C]leucine in all muscles. (2) The rate of oxidative decarboxylation of L-[1-14C]glutamine increased with increasing intracellular concentrations of glutamine. (3) The activities of glutamine aminotransferases K and L were more than 10-fold greater in rat than in chick skeletal muscles. (4) Mitochondrial phosphate-activated glutaminase activity was approx. 10-fold greater in chick than in rat skeletal muscles and increased with increasing glutamine concentrations. (5) An inhibitor of glutaminase, 6-diazo-5-oxo-L-norleucine, inhibited the rate of glutamine decarboxylation in chick, but not in rat, skeletal muscle. These findings suggest that glutamine degradation in skeletal muscle may be substantial and may make an important contribution to the regulation of intramuscular glutamine concentrations. A species difference in the pathways and the subcellular location for the conversion of glutamine into 2-oxoglutarate in rat and chick skeletal muscles is implied by the relative activities of glutamine-degrading enzymes.

Animals↗

PubMed1991

Prostaglandin synthesis and fatty acid composition of phospholipids and triglycerides in skeletal muscle of chicks fed combinations of flaxseed oil and animal tallow.

Chicks were fed isocaloric and isonitrogenous diets containing 6% (w/w) added fat consisting of various proportions of animal tallow and flaxseed oil (FSO). No differences among treatments were seen in growth rate, muscular deposition of protein and lipids nor in the muscle phospholipid (PL) and triglyceride (TG) contents. Prostaglandin (PG)E2 synthesis in isolated skeletal muscle was depressed significantly by feeding FSO or by treatment with naproxen (6-methoxy-alpha-methyl-2-napthaleneacetic acid), an inhibitor of PG synthesis. The changes associated with diet may be related to differences in the fatty acid composition of muscle lipids. Levels of saturated fatty acids in muscle PL and TG were relatively insensitive to dietary treatments. Monounsaturated fatty acid levels were significantly lower in the FSO-fed groups. FSO diets caused significant depression in muscle PL 20:4 omega 6 and almost completely inhibited 22:5 omega 6 incorporation. FSO diets decreased ratios of omega 6/omega 3 fatty acids and increased the unsaturation index of muscle PL. Muscles of chicks fed FSO showed increased levels of 18:3 omega 3, and of its derivatives 20:4 omega 3 and 22:5 omega 3. These results suggest that FSO inhibits PG synthesis and modifies the fatty acids of PL and TG of chick muscle. These changes may have implications for PG-dependent and/or membrane-dependent processes in muscle metabolism.

Animals↗

PubMed1991

Tissue protein synthesis in lactating and dry goats.

Intravenous infusion of L-[3H]phenylalanine (Phe) was carried out for 8 h in dry, non-pregnant and lactating dairy goats. Nitrogen balance was positive in the dry group and negative in the lactating group. Whole-body Phe flux was 50% greater in lactating goats (P less than 0.01). Fractional synthesis rates (Ks) of tissue proteins were estimated from plasma- (Ksp) and tissue- (Ksh) specific radioactivities of Phe. In lactating goats, Ksp for mammary gland, duodenum and diaphragm was increased (P less than 0.05). Ksp also tended to increase in liver, kidney and rumen (P less than 0.08) of lactating goats, but was not different in uterus, spleen, caecum or heart. Values of Ksh were higher than Ksp; however, these measures agreed qualitatively. When absolute rates of protein synthesis were calculated, an increased contribution of mammary and visceral organs was seen in lactating goats. Ks and absolute rates of protein synthesis of hind-limb skin were less in lactating goats (P less than 0.05). A decreased proportion of skeletal muscle (P less than 0.05). Decreased rates of muscle and skin protein synthesis would appear to participate in alterations of protein metabolism, permitting lactation to occur at the expense of body reserves.

Animals↗

PubMed1991

Effect of systemic inhibition of prostaglandin synthesis on muscle protein balance after trauma in the rat.

Anaesthetized rats were subjected to a single impact trauma to the medial aspect of the right hindlimb (gastrocnemius muscle), and were compared with sham-treated controls. For 3 days after injury, muscles of the traumatized limb showed a marked catabolic response. Muscle protein repletion commenced after day 3, however, this process was not complete until 21 days after injury. Muscles of the uninjured limb of the traumatized rats also showed a distinct catabolic response, compared with rats that were never injured, although this response was less in magnitude than that of the injured limb. At 3 days after trauma, augmented synthesis of prostaglandin (PG)E2 by muscles of the injured and uninjured limb provided evidence of a local and systemic inflammatory response. Inhibition of PG synthesis by the systemic administration of naproxen (6-methoxy-alpha-methyl-2-napthaleneacetic acid) significantly reduced the catabolic loss of muscle protein seen locally and peripherally to the injury site.

Anesthesia↗

PubMed1991

Influence of dietary flaxseed oil on the performance, muscle protein deposition, and fatty acid composition of broiler chicks.

Experiments were conducted to assess the effect of feeding flaxseed oil on the performance, muscle protein deposition, and fatty acid composition of broiler chicks. Four levels of dietary flaxseed oil were fed in combination with animal tallow to give a total of 6% added fat in the diets. The diets were isonitrogenous and isocaloric. Mortality, weight gain, feed consumption, and feed efficiency were not significantly different among treatments. Dietary treatments had no significant effects on the relative weights of the Extensor digitorum communis and Sartorius muscles nor on their protein or lipid contents. Feeding flaxseed oil resulted in increased accumulation of omega 3 fatty acids in skeletal muscle lipids. Increased amounts of desaturation and elongation products (C20:3, C20:5, C22:5, and C22:6) of alpha-linolenate (C18:3 omega 3) were observed in the Sartorius muscle lipids of chicks fed flaxseed oil. Amounts of these omega 3 fatty acids increased with duration of feeding. The amounts of omega 6 fatty acids (C20:2, C20:3, C20:4) were significantly depressed in muscle lipids after 21 days of feeding flaxseed oil. The effects of flaxseed oil on tissue amounts of individual saturated fatty acids were minimal, but amounts of monounsaturated fatty acids, especially C18:1, were depressed.

Animals↗

PubMed1990

Molecular evidence for the presence of growth hormone receptors in the bovine mammary gland.

GH receptor messenger RNA (mRNA) was identified and characterized in mammary tissue from normal and GH-treated lactating cows using Northern and in-situ hybridization analyses. One major GH receptor transcript of 4.4 kilobases and a less abundant transcript of 9.2 kilobases were detected in mammary tissue from both normal and GH-treated cows. In-situ hybridization analysis revealed that the GH receptor gene is primarily expressed in the alveolar epithelial cells of mammary tissue. These results are evidence that the lactating mammary gland may synthesize GH receptors. On the basis of these observations it seems likely that the lactating bovine mammary gland is a GH target tissue. This finding challenges the widely accepted view that GH does not directly regulate mammary growth or function.

Animals↗

PubMed1990

Ultrastructural events following acute muscle trauma.

The purpose of this study was to determine the ultrastructural events occurring in skeletal muscle following acute blunt trauma. Male rats weighing 250 g were subjected to a single impact trauma to the medial gastrocnemius muscle while under general anesthesia. Hemorrhage, inflammation, non-necrotic degeneration, and later regeneration were observed. In the short term following impact (6-24 h), the damaged segments showed gross tearing and degeneration. A large number of mononuclear cells were seen in the intercellular connective tissue and within the damaged muscle cells. By 24-48 h, there was an increase in the number of sarcolemmal nuclei, some of which were likely of satellite cell origin. By day 3, regenerating muscle cells displayed central nuclei and reorganizing sarcomeres. By day 6, further progression of regeneration was seen. Moreover, focal interstitial collagen formation suggested minimal to mild scar formation. On days 14, 21, and 30 after trauma, the muscle appeared to have healed and no abnormalities could be found at the site of injury. In parallel with the ultrastructural events noted, the injured muscles underwent a marked catabolic response and showed a reproducible fall (-27%, P less than 0.001) in total protein content within 48 h. Muscle protein accumulation commenced after day 3; however, complete repletion of the loss did not occur until day 21 post-injury.

Animals↗

PubMed1989

Prostaglandin-dependent muscle wasting during infection in the broiler chick (Gallus domesticus) and the laboratory rat (Rattus norvegicus).

Systemic infection with Escherichia coli significantly decreased feed intake, slowed growth of the whole body and skeletal muscles, and severely inhibited muscle protein accumulation in both chicks and rats. Treatment with naproxen (6-methoxy-alpha-methyl-2-naphthaleneacetic acid), an inhibitor of prostaglandin production, decreased weight losses of body and muscle, and significantly inhibited muscle protein wasting in infected chicks and rats. E. coli infection increased net protein degradation by 44.8% (P less than 0.05) and prostaglandin E2 production by 148% (P less than 0.05) in isolated extensor digitorum communis muscle from chicks on day 2 after infection. Naproxen treatment significantly decreased net protein degradation and prostaglandin E2 production in infected chicks to values seen in muscles of healthy controls. Quantitatively and qualitatively similar results were seen in isolated rat epitrochlearis muscle.

Animals↗

PubMed1989

An in vitro preparation of the extensor digitorum communis muscle from the chick (Gallus domesticus) for studies of protein turnover.

1. Extensor digitorum communis (EDC) muscles from the chick synthesized and degraded proteins at linear rates, and maintained high levels of ATP, creatine phosphate and glycogen, for 9 hr of incubation. 2. The apparent viability of the EDC preparation was improved by the provision of a continuous supply of oxygen, glucose, insulin and amino acids at the levels found in chick plasma, and incubation at 33.5 degrees C. 3. Incubated muscles were in net negative protein balance; however, under optimal conditions, this represented only 0.03% of total protein/hr. Rates of protein synthesis in the EDC preparation were 65% of those determined in vivo, comparing favourably with values obtained by other workers in mammalian muscle. 4. Rates of protein synthesis responded to insulin, amino acids, and to the nutritional status of the bird, as had been observed in prior studies with mammalian muscle. By contrast to mammalian muscle protein degradation was relatively insensitive to these modifiers.

Adenosine Triphosphate↗

PubMed1989

Effect of Escherichia coli infection on growth and protein metabolism in broiler chicks (Gallus domesticus).

1. A controlled experimental Escherichia coli infection was developed in broiler chicks. 2. Infection with E. coli significantly reduced feed intake, altered growth of the whole body, eviscerated carcass, skeletal muscles, heart and liver. Organ weight and/or the proportions of organs within the body were affected. 3. Protein accumulation in the eviscerated carcass, extensor digitorum communis and sartorius muscles was severely inhibited by infection, and to a greater extent than body weight. 4. Failure of muscle tissue to accumulate protein was associated with a significant decline in protein synthesis, when measured in vitro (-48%; P less than 0.05) and in vivo (-42%; P less than 0.001). Protein degradation also declined (-28.7%), but to a smaller extent than protein synthesis. 5. Although the infected chicks showed no viable bacteria at day 12 after infection, chicks did not reach the same body weight as controls by day 30 after infection.

Animals↗

PubMed1989

Influence of dietary carbohydrate-to-fat ratio on whole body nitrogen retention and body composition in adult rats.

Experiments have shown that the amount and source of dietary energy may alter protein metabolism. A high fat diet has resulted in greater nitrogen retention than a high carbohydrate (CHO) diet. To examine this question further, adult rats were fed diets providing ratios of CHO:FAT as a percentage of energy of 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 for 6 wk. Mean energy and protein intakes were 93.0 +/- 0.8 kcal/d and 5.3 +/- 0.1 g/d, respectively. Final body weight was lower in rats fed the high fat diet (CHO:FAT, 0.5) than in rats fed the high carbohydrate diet (CHO:FAT, 3.0) (P less than 0.05), and a linear response was observed over the entire range of treatments (r = 0.92). Rats fed the high fat diet had the highest nitrogen balance; values were significantly (P less than 0.05) different from those of rats fed high carbohydrate diets (CHO:FAT, 2.0 or 2.5) when expressed as mg nitrogen/kcal energy gain. Rats fed the high fat diet had the highest protein gain and the lowest fat gain as a function of energy gain. It is concluded that alterations in nonprotein energy source result in metabolic changes, which may be related to adaptations in energy expenditure and/or protein deposition.

Animals↗

PubMed1989

Exercise inhibits progressive growth of the Morris hepatoma 7777 in male and female rats.

Male and female rats were either trained to swim for a 6-week period or they remained sedentary. Rats were implanted with Morris hepatoma 7777 after 3 weeks of swimming and were sacrificed after a further 3 weeks. Exercised rats of both sexes showed a significant reduction in tumour weight at sacrifice, compared with sedentary controls (p less than 0.01). Similarly, when rats were first implanted with tumours and then placed on an exercise program of 3 weeks duration, tumour growth was also reduced (p less than 0.05). These results suggest that the tumour may be sensitive to exercise at more than one point in its development. Tumour growth was inhibited to a similar extent whether the total swimming time was 10, 20, or 30 h over the 3-week period. Although sedentary, tumour-bearing rats were anorexic; both male and female rats showed significant improvement of appetite during the period of tumour growth, in response to exercise. Tumour implantation was associated with significant losses of whole body and muscle protein. The progression of this wasting was not significantly altered by exercise.

Animals↗

PubMed1989

Effects of systemic inhibition of prostaglandin production on protein metabolism in tumor-bearing rats.

Two rat tumors, Morris hepatoma 7777 (MH) and Yoshida ascites hepatoma AH130 (YAH) were compared, and the influence of systemic inhibition of prostaglandin (PG) synthesis on muscle protein metabolism was evaluated. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats were also treated with naproxen, an inhibitor of PG synthesis. Tumors caused progressive anorexia and weight loss and resulted in decreased weight and/or protein content of the soleus, extensor digitorum longus, and epitrochlearis muscles. The extent of this wasting varied with muscle and tumor type. Muscle wasting induced by the tumors appeared to result from increased protein degradation and/or decreased protein synthesis, as determined in isolated epitrochlearis muscle. In YAH, reduced feed intake did not appear to be responsible for muscle wasting; however, in MH, it accounted for a significant proportion of the muscle loss. YAH produced large amounts of PGE2. Treatment of rats with naproxen inhibited tumor PGE2 production and muscle protein loss in rats bearing YAH. Naproxen had no effect on muscle weight or protein degradation in rats bearing MH. These results would appear to implicate PGE2 in the development of cachexia in the laboratory rat.

Amino Acids↗