Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac cells obtained from neonatal rat heart contain a mixed population of cell types that can be enriched in culture in either myocytes or fibroblast-like cells. A metabolic comparison of mixed heart cell cultures with enriched cultures of the same age-in-culture and initial cell density showed that mixed cultures used glucose more rapidly than either enriched myocytes or fibroblasts. Mixed cultures were shown to respond to deprivation of insulin and of serum with decreases in the rate of glucose usage and decreases in the protein content of cells, whereas enriched cultures did not respond in the expected manner to insulin deprivation. Mixed, 11-day-old cells also exhibited greater increases in cellular protein and greater resistance to the stress of starvation than enriched cultures. Palmitate usage, however, was similar in all cultures examined. We conclude that mixed cultures may serve as a better model system to study cardiac metabolism and to monitor the effects of drugs and hormones on the neonatal myocardium. In addition, it is clear from our results that myocytes and fibroblastic-like cells coexist in a metabolically functional synergism.
 ...
PMID:Myocytes and fibroblasts exhibit functional synergism in mixed cultures of neonatal rat heart cells. 636 Oct 43

This study was designed to ascertain whether the overall availability of whole-body lipids and nitrogen is a limiting factor for survival in tumor-bearing mice suffering from anorexia and cachexia. Three-month-old nongrowing mice (C57BL/6J) were given s.c. transplants of a methylcholanthrene-induced sarcoma. Freely fed, starved, and pair-fed animals were used. Body and lipid composition, tumor growth, and survival time were measured. Freely fed sarcoma-bearing mice died with profoundly altered body composition. This was not explained by the anorexia assessed in pair-feeding experiments. Starvation had caused a more severe depletion in body composition in both tumor-bearing and nontumor-bearing animals than the tumor alone did in freely fed tumor-bearing mice. Freely fed tumor-bearing animals had normal proportions of whole-body triglycerides, cholesterol, and polar lipids, but they lost palmitic acid quantitatively more than any other fatty acid. It is unlikely that any single fatty acid became limiting during tumor growth. The results show that the overall availability of lipids, nitrogen, and glucose precursors is not a limiting factor for survival in experimental tumor cachexia. Other factors considered to be more likely as determining factors for the death of tumor-bearing animals are discussed.
 ...
PMID:Role of whole-body lipids and nitrogen as limiting factors for survival in tumor-bearing mice with anorexia and cachexia. 657 17

The conversion of radioactive C6-C16-monocarboxylic acids to urinary adipic, suberic, sebacic and 3-hydroxybutyric acids was investigated in vivo in unstarved, starved and diabetic ketotic rats. Hexanoic, octanoic and decanoic acids were converted to C6-, C6-C8- and C6-C10-dicarboxylic acids, respectively, in fed and 72-h-starved rats. Lauric acid was converted to C6-C8-dicarboxylic acids in starved rats but not in unstarved rats. Decanoic and lauric acids were converted to relatively high amounts of C6-C8-dicarboxylic acids compared with myristic acid in myristic acid in ketotic diabetic rats, while radioactivity from [1-14C]-and [16-(14)] palmitic acid was not incorporated into C6-C8-dicarboxylic acids in diabetic ketotic rats. C6-C12-monocarboxylic acids in hydrolysed rat adipose tissue wee determined by gas-liquid chromatography-mass spectrometry (selected ion monitoring). Decanoic and lauric acids were found in amounts of 7.6-9.1 and 85.9-137.5 micrometers/100 mg tissue, respectively, whereas the amounts of hexanoic and octanoic acids were negligible. It is concluded that the biological origin of the C6-C8-dicarboxylic aciduria seen in ketotic rats are C10-C14-monocarboxylic acids, which are initially omega-oxidised solely or partly as free acids and subsequently beta-oxidised to adipic and suberic acids. The in vitro omega-oxidation of C6-C16-monocarboxylic acids to corresponding dicarboxylic acids in the 100,000 Xg supernatant fraction of rat liver homogenate was measured by selected ion monitoring. 0.09, 0.14, 16.1, 5.8, 7.0 and -6.9% of, respectively, hexanoic, octanoic, decanoic, lauric, myristic and palmitic acid were omega-oxidised to dicarboxylic acids of corresponding chain lengths after 90 min of incubation, when correction for the production of dicarboxylic acids in control assays was made. An in vitro production of C12-C16-dicarboxylic acids was detected in all assays ()including control assays), probably formed from"endogenous' monocarboxylic acids preexistent in the homogenate. Ths "endogenous' production of dicarboxylic acids was inhibited by C10-C16-monocarboxylic acids, where palmitic acid had the strongest effect. In fact, palmitic acid inhibited its own omega-oxidation when added in concentrations above 0.6 mM. Starvation of rats for 72 h did not alter the "endogenous' in vitro production of hexadecanedioic acid.
 ...
PMID:The biological origin of ketotic dicarboxylic aciduria. In vivo and in vitro investigations of the omega-oxidation of C6-C16-monocarboxylic acids in unstarved, starved and diabetic rats. 679 96

Cell growth of Saccharomyces cerevisiae ATCC 12341 inhibited by the antibiotic cerulenin, a specific inhibitor of fatty acid synthesis, was restored by oleic acid (18 : 1) to give saturated fatty acid-starved cells, which could not grow when again transferred into a fresh synthetic medium containing the antibiotic and oleic acid. The growth of the saturated fatty acid-starved cells was restored when they were transferred into a medium supplemented with myristic acid (14 : 0), pentadecanoic acid (15 : 0), and palmitic acid (16 : 0) in the presence of cerulenin and oleic acid. Cellular saturated fatty acid content in the growth-restored cells was also restored to about two-thirds of that of the normal yeast cells. The DNA, RNA, and cell wall synthetic capabilities of the saturated fatty acid-starved cells were almost normal, but the L-leucine uptake and cytochrome pattern were severely impaired. These impairments were reversed on supplying palmitic acid. The decrease of L-leucine uptake of the yeasts was also caused by the addition of cerulenin alone. However, since the decrease occurred later than the inhibition of fatty acid synthesis, it was considered to be a secondary effect. These results, obtained by using the saturated fatty acid-starved cells, indicate that the membranes of S. cerevisiae require certain amounts of saturated fatty acid and that the membrane functions (energy metabolism, transport, and so on) are impaired by starvation of saturated fatty acids.
 ...
PMID:Saturated fatty acid-starved cells of Saccharomyces cerevisiae grown in the presence of cerulenin and oleic acid. 701 49

Intravenous administration of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid had no effect on the proportion of pyruvate dehydrogenase complex in the active form in heart, diaphragm or gastrocnemius muscles or in liver, kidney or adipose tissue of fed normal rats. The compound reversed the effect of 48h starvation (which decreased the proportion of active complex) in heart muscle, partially reversed the effect of starvation in kidney, but had no effect in the other tissues listed. The compound failed to reverse the effect of alloxan-diabetes (which decreased the proportion of active complex) in any of these tissues. In perfused hearts of fed normal rats, 2-tetradecylglycidate reversed effects of palmitate (which decreased the proportion of active complex), but it had no effect in the absence of palmitate. In perfused hearts of 48h-starved rats the compound increased the proportion of active complex to that found in fed normal rats in the presence or absence of insulin. In perfused hearts of diabetic rats the compound normalized the proportion of active complex in the presence of insulin, but not in its absence. Palmitate reversed the effects of 2-tetradecylglycidate in perfused hearts of starved or diabetic rats. Evidence is given that 2-tetradecylglycidate only reverses effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle under conditions in which it inhibits fatty acid oxidation. It is concluded that effects of starvation and alloxan-diabetes on the proportion of active complex in heart muscle are dependent on fatty acid oxidation. Insulin had no effect on the proportion of active complex in hearts or diaphragms of fed or starved rats in vitro. In perfused hearts of alloxan-diabetic rats, insulin induced a modest increase in the proportion of active complex in the presence of albumin, but not in its absence.
 ...
PMID:Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats. 715 98

The effect of plasma glucose and nonesterified fatty acid (NEFA) on basal and insulin-stimulated glucose utilization in skeletal muscle was assessed by perfused hindlimb preparations. Two-month-old male Wistar rats were divided into four groups: starved, glucose-loaded, hypoglycemic and control. Diabetic rats were made by means of streptozotocin, and divided into three groups: non-treated, insulin-treated normoglycemic and insulin-treated hyperglycemic. The effect of NEFA on glucose clearance was also investigated by adding palmitate to the perfusate. Basal glucose utilization decreased with a rise in plasma glucose concentrations, and increased with a fall in them in each group. The available data strongly support the view that plasma glucose levels play an important role in the control of basal glucose utilization by the hindlimb muscle. In contrast, continuous hyperglycemia in the diabetic state decreased insulin-stimulated glucose utilization by the skeletal muscle, whereas an acute rise in plasma glucose concentrations in the glucose-load state did not. Palmitate stimulated basal glucose utilization, while it decreased insulin-stimulated glucose uptake. It was also clarified that it increased the affinity for glucose in the skeletal muscle in the basal state. This finding seems to indicate that NEFA has some influence on an increase in basal glucose utilization in starvation.
 ...
PMID:Can plasma glucose and nonesterified fatty acid be regulators of glucose utilization in skeletal muscle? 795 69

Transcription of acetyl-CoA carboxylase in avian liver is low during starvation or after consumption of a low-carbohydrate, high-fat diet and high during consumption of a high-carbohydrate, low-fat diet. The role of fatty acids or metabolites derived from fatty acids in the nutritional control of acetyl-CoA carboxylase transcription was investigated by determining the effects of long- and medium-chain fatty acids on acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes. Palmitate, oleate, and arachidonate caused a decrease in acetyl-CoA carboxylase activity in hepatocytes incubated with triiodothyronine (T3). The inhibition of acetyl-CoA carboxylase activity caused by arachidonate was accompanied by a similar decrease in transcription of the acetyl-CoA carboxylase gene. In contrast, neither palmitate nor oleate were effective in modulating acetyl-CoA carboxylase transcription. These results are consistent with arachidonate or a metabolite derived therefrom mediating the effects of diets containing high levels of n-6 polyunsaturated fatty acids on acetyl-CoA carboxylase transcription in liver. Hexanoate and octanoate also inhibited acetyl-CoA carboxylase activity in the presence of T3. The magnitude of the hexanoate- or octanoate-induced decrease in acetyl-CoA carboxylase activity was greater than that observed for long-chain fatty acids. Hexanoate and octanoate inhibited acetyl-CoA carboxylase activity at a transcriptional step, and did so within 2 h of addition of fatty acid. Addition of carnitine partially reversed the inhibitory effects of octanoate on acetyl-CoA carboxylase expression, suggesting that a metabolite of octanoate is involved in mediating this response. 2-Bromooctanoate was a more potent inhibitor of acetyl-CoA carboxylase expression than octanoate or hexanoate. We postulate that a metabolite of hexanoate and octanoate, possibly a six or eight carbon acyl-CoA, plays a role in the nutritional regulation of acetyl-CoA carboxylase transcription.
 ...
PMID:Arachidonate and medium-chain fatty acids inhibit transcription of the acetyl-CoA carboxylase gene in hepatocytes in culture. 945 78

The aim of the present study was to investigate the hepatic regulation and beta-oxidation of long-chain fatty acids in peroxisomes and mitochondria, after 3-thia- tetradecylthioacetic acid (C14-S-acetic acid) treatment. When palmitoyl-CoA and palmitoyl-L-carnitine were used as substrates, hepatic formation of acid-soluble products was significantly increased in C14-S-acetic acid treated rats. Administration of C14-S-acetic acid resulted in increased enzyme activity and mRNA levels of hepatic mitochondrial carnitine palmitoyltransferase (CPT)-II. CPT-II activity correlated with both palmitoyl-CoA and palmitoyl-L-carnitine oxidation in rats treated with different chain-length 3-thia fatty acids. CPT-I activity and mRNA levels were, however, marginally affected. The hepatic CPT-II activity was mainly localized in the mitochondrial fraction, whereas the CPT-I activity was enriched in the mitochondrial, peroxisomal, and microsomal fractions. In C14-S-acetic acid-treated rats, the specific activity of peroxisomal and microsomal CPT-I increased, whereas the mitochondrial activity tended to decrease. C14-S-Acetyl-CoA inhibited CPT-I activity in vitro. The sensitivity of CPT-I to malonyl-CoA was unchanged, and the hepatic malonyl-CoA concentration increased after C14-S-acetic acid treatment. The mRNA levels of acetyl-CoA carboxylase increased. In hepatocytes cultured from palmitic acid- and C14-S-acetic acid-treated rats, the CPT-I inhibitor etomoxir inhibited the formation of acid-soluble products 91 and 21%, respectively. In contrast to 3-thia fatty acid treatment, eicosapentaenoic acid treatment and starvation increased the mitochondrial CPT-I activity and reduced its malonyl-CoA sensitivity. Palmitoyl-L-carnitine oxidation and CPT-II activity were, however, unchanged after either EPA treatment or starvation. The results from this study open the possibility that the rate control of mitochondrial beta-oxidation under mitochondrion and peroxisome proliferation is distributed between an enzyme or enzymes of the pathway beyond the CPT-I site after 3-thia fatty acid treatment. It is suggested that fatty acids are partly oxidized in the peroxisomes before entering the mitochondria as acylcarnitines for further oxidation.
 ...
PMID:3-Thia fatty acid treatment, in contrast to eicosapentaenoic acid and starvation, induces gene expression of carnitine palmitoyltransferase-II in rat liver. 1038 Jan 16

beta-Ketoacyl-acyl carrier protein (ACP) synthase III (KAS III, also called acetoacetyl-ACP synthase) encoded by the fabH gene is thought to catalyze the first elongation reaction (Claisen condensation) of type II fatty acid synthesis in bacteria and plant plastids. However, direct in vivo evidence that KAS III catalyzes an essential reaction is lacking, because no mutant organism deficient in this activity has been isolated. We report the first bacterial strain lacking KAS III, a fabH mutant constructed in the Gram-positive bacterium Lactococcus lactis subspecies lactis IL1403. The mutant strain carries an in-frame deletion of the KAS III active site region and was isolated by gene replacement using a medium supplemented with a source of saturated and unsaturated long-chain fatty acids. The mutant strain is devoid of KAS III activity and fails to grow in the absence of supplementation with exogenous long-chain fatty acids demonstrating that KAS III plays an essential role in cellular metabolism. However, the L. lactis fabH deletion mutant requires only long-chain unsaturated fatty acids for growth, a source of long-chain saturated fatty acids is not required. Because both saturated and unsaturated fatty acids are required for growth when fatty acid synthesis is blocked by biotin starvation (which prevents the synthesis of malonyl-CoA), another pathway for saturated fatty acid synthesis must remain in the fabH deletion strain. Indeed, incorporation of [1-14C]acetate into fatty acids in vivo showed that the fabH mutant retained about 10% of the fatty acid synthetic ability of the wild-type strain and that this residual synthetic capacity was preferentially diverted to the saturated branch of the pathway. Moreover, mass spectrometry showed that the fabH mutant retained low levels of palmitic acid upon fatty acid starvation. Derivatives of the fabH deletion mutant strain were isolated that were octanoic acid auxotrophs consistent with biochemical studies indicating that the major role of FabH is production of short-chain fatty acid primers. We also confirmed the essentiality of FabH in Escherichia coli by use of a plasmid-based gene insertion/deletion system. Together these results provide the first genetic evidence demonstrating that FabH conducts the major condensation reaction in the initiation of type II fatty acid biosynthesis in both Gram-positive and Gram-negative bacteria.
 ...
PMID:Beta-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis. 1452 10

Rat hearts were perfused for 1 h with 5 mm glucose with or without palmitate or oleate at concentrations characteristic of the fasting state. The inclusion of fatty acids resulted in increased activities of the alpha-1 or the alpha-2 isoforms of AMP-activated protein kinase (AMPK), increased phosphorylation of acetyl-CoA carboxylase and a decrease in the tissue content of malonyl-CoA. Activation of AMPK was not accompanied by any changes in the tissue contents of ATP, ADP, AMP, phosphocreatine or creatine. Palmitate increased phosphorylation of Thr172 within AMPK alpha-subunits and the activation by palmitate of both AMPK isoforms was abolished by protein phosphatase 2C leading to the conclusion that exposure to fatty acid caused activation of an AMPK kinase or inhibition of an AMPK phosphatase. In vivo, 24 h of starvation also increased heart AMPK activity and Thr172 phosphorylation of AMPK alpha-subunits. Perfusion with insulin decreased both alpha-1 and alpha-2 AMPK activities and increased malonyl-CoA content. Palmitate prevented both of these effects. Perfusion with epinephrine decreased malonyl-CoA content without an effect on AMPK activity but prevented the activation of AMPK by palmitate. The concept is discussed that activation of AMPK by an unknown fatty acid-driven signalling process provides a mechanism for a 'feed-forward' activation of fatty acid oxidation.
 ...
PMID:Covalent activation of heart AMP-activated protein kinase in response to physiological concentrations of long-chain fatty acids. 1515 11


<< Previous 1 2 3 4 Next >>