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Mobilization and recovery of energy stores in traíra, Hoplias malabaricus Bloch (Teleostei, Erythrinidae) during long-term starvation and after re-feeding.

In some neotropical environments, fishes often experience periods of poor food supply, especially due to extreme fluctuations in rainfall regime. The fish species that experience periods of drought such as the traíra Hoplias malabaricus (Bloch 1794), may stand up to long-term food deprivation. In this study, experiments were performed in order to determine the dynamic of utilization of endogenous reserves in this species during starvation. Adult traíra were both fasted for 30-240 days and re-fed for 30 days following 90 and 240 days of fasting. Glycogen and perivisceral fat were primary energy substrates consumed. During the first 30 days, fish consumed hepatic and muscular glycogen, without exhausting these reserves, and used lipids from perivisceral fat. Hepatic lipids were an important energy source during the first 60 days of starvation and perivisceral fat were consumed gradually, being exhausted after 180 days. Protein mobilization was noticeable after 60 days of fasting, and became the major energy source as the lipid reserves were decreased (between 90 and 180 days). Following the longest periods of food deprivation, fish had utilized hepatic glycogen again. Fish re-fed for 30 days after 90 and 240 days of fasting were able to recover hepatic glycogen stores, but not the other energy reserves.

Adipose Tissue↗

Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation.

We investigated the effects of acute starvation on mitogen-induced T-cell activation and Th1/Th2 cytokine responses in rheumatoid arthritis (RA) patients. Ten RA patients with active disease underwent a 7-day fast followed by a 2-week refeeding period. Immunological, hormonal, laboratory and clinical evaluations were carried out on days 0, 7 and 21. Using flow cytometry, mitogen-stimulated T-cell activation was assessed in fresh heparinised blood via analysis of CD69 expression. Production of Th1 (interferon-gamma) and Th2 (interleukin-4, IL-4) cytokines was also assessed by ELISA. The 7-day fast significantly decreased the erythrocyte sedimentation rate, C-reactive protein level, joint count, morning stiffness, body weight, CD4+ and CD8+ counts and CD69+ expression on mitogen stimulated CD4+ lymphocytes. A significant increase in mitogen-induced IL-4 production after fasting was found. The fast markedly reduced serum leptin and insulin-like growth factor-1 concentrations. No significant differences occurred in serum cortisol or prolactin before and after fasting. Decreases in CD4+ lymphocyte activation during fasting correlated with decreases in body weight. Our results suggest that the clinical and laboratory improvements in fasting RA patients may be attributed to decreased CD4+ T-cell activation and an increase in the number and/or function of IL-4-producing Th2 cells. Factors associated with loss of body weight during acute starvation appear to have an inhibitory effect on CD4+ lymphocyte activation.

Adult↗

beta-Galactosidase activity of Escherichia coli under long-term starvation, alterations in temperature, and different nutrient conditions in lake water.

beta-Galactosidase activity of Escherichia coli was investigated in response to long-term starvation, changes in temperature and the presence of certain nutrient sources in lake water. beta-Galactosidase activity decreased markedly in filtered-autoclaved lake water at 25 degrees C and 37 degrees C, whereas it remained almost constant at 4 degrees C and 15 degrees C for 60 days. Increases in beta-galactosidase activity were observed in response to the following nutrient sources: glycine, serine, methionine and ammonium sulfate at 4 degrees C; glycine and ammonium sulfate at 15 degrees C; glycine, serine, methionine and ammonium sulfate at 30 degrees C. Glycine addition led to an increase in beta-galactosidase activity of almost five and seven orders of magnitude at 15 degrees C and 30 degrees C, respectively. In addition, L-methionine had the strongest influence on beta-galactosidase activity, which was detected as an increase of seven and eleven orders of magnitude at 4 degrees C and 30 degrees C, respectively. The effect of several amino acids and other nitrogen sources depended on the concentration of the nutrient source and the temperature. The results showed that, in lake water, long-term starvation, temperature change, and variations in nitrogen sources alter beta-galactosidase activity. Those effects should be taken into account when monitoring coliforms from the environment.

Amino Acids↗

Lipid and fatty acid composition of brush border membrane of rat intestine during starvation.

Alterations in the lipid and fatty acid composition of brush border membrane (BBM) of small intestine were studied in well-fed, starved, and refed rats. The ratios of cholesterol/phospholipid (mol/mol), sphingomyelin/phosphatidylcholine (mol/mol), protein/lipid (w/w), and free fatty acids (w/w) decreased whereas the total phospholipid (w/w) ratio and the double-bond index increased in BBM of the intestine of the starved rat compared to that of the well-fed rat. Analyses of fatty acids showed higher percentage of stearic and arachidonic acids whereas oleic and linoleic acids decreased under starvation. The acyl chain of starved rat BBM was less ordered compared with that of well-fed rat BBM. On refeeding, these changes were restored to well-fed levels. The change in membrane state under starvation is associated with alterations in the lipid and fatty acid composition of BBM and may be responsible for functional changes that occur under nutritional stress.

Animals↗

3-Thia fatty acid treatment, in contrast to eicosapentaenoic acid and starvation, induces gene expression of carnitine palmitoyltransferase-II in rat liver.

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.

Animals↗

Suppression of egg-laying during starvation in the snail Lymnaea stagnalis by inhibition of the ovulation hormone producing caudo-dorsal cells.

Starvation inhibits egg-laying in the snail, Lymnaea stagnalis. In starved animals the neurosecretory Caudo-Dorsal Cells (CDC), which produce the egg-laying hormone, are hyperpolarized as compared to the CDC of controls. However, they are more responsive to repetitive intracellular stimulation, which induces the hormone releasing discharge. Hyperpolarization is not found in the non-neurosecretory Cerebral Giant Cells, which indicates that the effect is specific for the CDC. It is also a characteristic effect of starvation as compared to another treatment (dirty water) inhibiting egg-laying.

Animals↗

Brain tyrosine availability and the depression of central nervous norepinephrine turnover in acute and chronic starvation in adult male rats.

Norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MOPEG) were determined in medio-basal hypothalamus of adult male rats using high-performance liquid chromatography to study nutritional modulation of noradrenergic turnover. Acute starvation, as well as 3 weeks of semistarvation with a low-protein high-carbohydrate or high-protein low-carbohydrate diet decreased NE turnover significantly, as estimated by MOPEG concentration. Low-protein semistarvation resulted in subnormal concentrations of large neutral amino acids (LNAA), high-protein semistarvation in elevated concentrations. Tyrosine/LNAA ratio and calculated tyrosine flow into brain and brain tyrosine levels were reduced in both types of semistarvation. Corticosterone was low in low-protein and high in high-protein diet. These results suggest that tyrosine availability in brain potentially contributes to reduced NE turnover in starvation.

Animals↗

The roles of intrinsic kinase and of kinase/activator protein in the enhanced phosphorylation of pyruvate dehydrogenase complex in starvation.

Extracts of heart mitochondria from fed and from 48 h starved rats subjected to gel filtration on Sephacryl S-300 gave 4 major protein peaks. Pyruvate dehydrogenase complex eluted in the void volume and was assayed for intrinsic pyruvate dehydrogenase kinase activity which was increased approximately 3-fold by 48 h starvation of the rat. A second fraction, containing peaks 2 and 3 which overlapped, enhanced the activity of the intrinsic kinase and corresponds to kinase/activator protein described previously. Its activity was increased 1.5-fold by starvation.

Adenosine Triphosphate↗

Effect of starvation and insulin in vivo on the activity of the pyruvate dehydrogenase complex in rat skeletal muscles.

The in vivo responses of pyruvate dehydrogenase (PDH) complex to starvation and insulin was assessed in heart, diaphragm and red quadriceps muscle. PDH complex activity was decreased by starvation (3.4-10.2-fold), the magnitude of change depending on muscle type. Insulin increased PDH activity in all muscle types. In fed rats, this effect was relatively small (1.25-1.29-fold). In starved rats there were effects in heart (4.3-fold) and red quadriceps (1.7-fold) but no effect in diaphragm. These results demonstrate that PDH complex in different groups of muscle has different insulin sensitivity (particularly in tissues from starved animals).

Adipose Tissue, Brown↗

Pyruvate inhibition of pyruvate dehydrogenase kinase. Effects of progressive starvation and hyperthyroidism in vivo, and of dibutyryl cyclic AMP and fatty acids in cultured cardiac myocytes.

Both prolonged starvation and hyperthyroidism evoke stable increases in cardiac pyruvate dehydrogenase kinase (PDHK) activity. Pyruvate inhibits PDHK in rat heart mitochondria with activation of PDHC. The sensitivity of PDHK to inhibition by pyruvate declines after prolonged starvation. In the present study, pyruvate concentrations giving 50% active complex (PDHa) in mitochondria from fed, control and fed, hyperthyroid rats were 0.3 and 0.8 mM, respectively, compared with 1.0 and 2.8 mM, respectively in mitochondria from 24-h-starved and 48-h-starved rats. The results demonstrate that altered pyruvate sensitivity is not of necessity linked with altered PDHK activity. PDHK activities in mitochondria prepared from cardiac myocytes from fed rats were increased after culture for 24 h with dibutyryl cyclic AMP (50 microM) plus n-octanoate (1 mM), with a concomitant decline in sensitivity of PDHK to pyruvate inhibition, suggesting that changes in sensitivity of PDHK to pyruvate inhibition in vivo may be secondary to increased fatty acid supply and cyclic AMP concentrations.

Animals↗

Regulation of rat antral gastrin and somatostatin gene expression during starvation and after refeeding.

Antral gastrin and somatostatin gene expression during starvation and after refeeding with liquid meals of varying composition were studied. Northern and slot-blot hybridization analyses showed that starvation caused a marked decrease in antral gastrin messenger RNA (mRNA) level by 12 hours associated with an increase in somatostatin mRNA. After 48 hours of fasting, antral gastrin mRNA was 26% and somatostatin mRNA was 136% of their prefasting levels. Refeeding caused increased 2-hour integrated gastrin mRNA levels after liquid peptone (+45%), phenylalanine (+31%), and olive oil (+13%), but no changes were observed with glucose or saline solutions. Integrated 2-hour immunoreactive antral gastrin content was increased after peptone (+106%), phenylalanine (+68%), and olive oil (+32%) meals but was not increased after glucose (-11%) or saline (-10%). In some cases, both gastrin mRNA and peptide responses could be measured as early as 15 minutes. The same nutrients that increased gastrin mRNA levels caused decreased 2-hour integrated somatostatin mRNA levels; peptone (-30%), phenylalanine (-28%), and olive oil (-21%), but neither glucose nor saline, altered somatostatin mRNA levels. These results suggest that antral gastrin and somatostatin genes were regulated in opposite directions, in a coordinate manner, by specific gastric nutrients that stimulate gastrin release.

Animals↗

The effects of thyroid hormones and starvation on hepatic mitochondrial nucleic acids of rainbow trout (Oncorhynchus mykiss).

Twenty four hours after an intraperitoneal injection of thyroxine (T4; 4.4, 44 ng/g body wt) or triiodothyronine (T3; 3.3, 33 ng/g body wt), DNA and RNA were significantly reduced in isolated liver mitochondria of rainbow trout. Total liver DNA was increased with the higher doses in both T4- and T3-injected specimens while total RNA was significantly reduced with the same doses. Total circulating plasma T4 was reduced with the injections of T3 or starvation, and plasma T3 was increased severalfold with the T3 injections. Plasma T4 also increased fivefold after a higher dose of T4 injection while starvation significantly reduced the concentration, when measured by radioimmunoassay.

Animals↗

Heterogeneity of glycogen synthesis upon refeeding following starvation.

1. Starvation of rats for 40 hr decreased the body weight, liver weight and blood glucose concentration. The hepatic and skeletal muscle glycogen concentrations were decreased by 95% (from 410 mumol/g tissue to 16 mumol/g tissue) and 55% (from 40 mumol/g tissue to 18.5 mumol/g tissue), respectively. 2. Fine structural analysis of glycogen purified from the liver and skeletal muscle of starved rats suggested that the glycogenolysis included a lysosomal component, in addition to the conventional phosphorolytic pathway. In support of this the hepatic acid alpha-glucosidase activity increased 1.8-fold following starvation. 3. Refeeding resulted in liver glycogen synthesis at a linear rate of 40 mumol/g tissue per hr over the first 13 hr of refeeding. The hepatic glycogen store were replenished by 8 hr of refeeding, but synthesis continued and the hepatic glycogen content peaked at 24 hr (approximately 670 mumol/g tissue). 4. Refeeding resulted in skeletal muscle glycogen synthesis at an initial rate of 40 mumol/g tissue per hr. The muscle glycogen store was replenished by 30 min of refeeding, but synthesis continued and the glycogen content peaked at 13 hr (approximately 50 mumol/g tissue). 5. Both liver and skeletal muscle glycogen synthesis were inhomogeneous with respect to molecular size; high molecular weight glycogen was initially synthesised at a faster rate than low molecular weight glycogen. These observations support suggestions that there is more than a single site of glycogen synthesis.

Animals↗

Starvation leads to decreased levels of mRNA for myofibrillar proteins.

Malnutrition is a common complicating factor in surgical illness. To investigate the cellular changes and mechanisms responsible for the protein wasting associated with nutritional deprivation, Sprague-Dawley rats were subjected to total protein-calorie starvation for 3 (n = 12) or 5 days (n = 12) and compared to freely fed animals monitored for 3 (n = 8) or 5 (n = 8) days. Gastrocnemius protein and RNA content and levels of mRNA coding for the myofibrillar proteins myosin heavy chain, myosin light chain, and alpha-actin were measured. Starvation resulted in a significant decrease in gastrocnemius mass and protein content, and was associated with decreases in mRNA levels for the three myofibrillar proteins assayed. We conclude that changes in mRNA levels for these proteins likely contribute to the loss of peripheral protein which occurs during total nutritional deprivation. In addition, the changes in mRNA levels for these three structural proteins appear to be coordinate, suggesting that transcription of no single myofibrillar protein is rate-limiting in the regulation of skeletal muscle protein content.

Actins↗

Decrease of the pool of amino acids adsorbed on blood cell membranes caused by starvation in rats.

The effect of 24 h starvation on the pool of amino acids adsorbed on the blood cell membranes was determined in Wistar rats. Aortic and iliac blood was analysed. 24 h starvation induced a significant decrease in the combined essential amino acids adsorbed on the blood cell membranes, in both arterial and venous blood, without affecting whole-blood levels (adsorbed + non-adsorbed). The same tendency was extended to most of the individual amino acids. This finding indicates that this pool of adsorbed amino acids has a rapid turnover and probably plays a physiological role in a situation of exogenous food deprivation.

Adsorption↗

Renal conservation of ketone bodies during starvation.

Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

Acetoacetates↗

Evidence for an accelerated adaptation to starvation in chronic uremia.

During a 72-hr period of starvation plasma levels of glucose and immunoreactive insulin fell to a greater extent, and alanine, free fatty acid, and glycerol concentrations were higher in fasted chronically uremic rats than in nonuremic controls. These changes, in conjunction with a significant increase in the uremic group's activity of phosphoenolypyruvate-carboxykinase, the rate-limiting enzyme in hepatic gluconeogenesis, after only 12 hr of fasting suggest that alterations in glucose metabolism in uremia may contribute to an exaggeration and acceleration of the metabolic consequences of starvation.

Adaptation, Physiological↗

Metabolic response to starvation. I. Relative effects of pregnancy and sex steroid administration in the rat.

Increased sensitivity to a fast with rapid onset of ketosis, hypoalaninemia, and hypoglycemia is characteristic of rat and human gestation. The present study examines the role of sex steroids in the development of these metabolic changes. Subgroups of female rate received 10 microgram of estradiol (E), 10 mg of progesterone (P), or the two in combination (E + P) s.c. daily for 5 days. Control rats (C) received sesame oil alone. Different groups were starved 12, 24 and 48 hr during days 4 and 5 or treatment. Plasma substrate and insulin responses were measured and compared to results of similar studies performed on rats in late gestation. Administration of E or P along had no significant effects on measured parameters as compared to control values. However, the combined E + P regimen resulted in significantly higher ketonemia, greater hypoalaninemia, and relatively higher triglyceride concentrations than in control groups during fasting. Plasma triglyceride, free fatty acid, and ketone concentrations in the pregnant group exceeded values of both the E + P and control animals. However, plasma free fatty acids in the E + P group were significantly lower as compared to control values during starvation. These data suggest that the combined effects of estradiol and progesterone enhance ketogenesis and hypoalaninemia independent of the fetal-placental unit during starvation in pregnancy. Since the ketogenic effect was associated with a relative suppression of plasma free fatty acids, this may be indicative of a direct action of these hormones on hepatic disposition of free fatty acids and/or the biosynthetic pathways for ketone body production.

Acetoacetates↗