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

This study evaluated the effect of 5 days of starvation followed by 5 days of refeeding on immunoreactive plasma and serum fibronectin and associated opsonic activity as studied by peritoneal macrophage monolayer bioassay in 12 healthy women volunteers. The temporal alteration of fibronectin was compared with the serum albumin, total iron-binding capacity, and retinol-binding protein levels. Fibronectin concentration and opsonic activity were also determined in two cachectic patients who were 61 and 78% of their ideal body weight. Prior to starvation, plasma fibronectin was 292 +/- 20 micrograms/ml and serum fibronectin was 182 +/- 16 in all subjects. After 5 days of starvation, immunoreactive fibronectin decreased (p less than 0.05) by 20-25%. This decrease was not great enough to impair opsonic activity as tested by the in vitro macrophage assay. Starvation caused no decrease in serum albumin or total iron-binding capacity, although retinol-binding protein decreased by 35%. During refeeding, subjects were randomized to a diet with (n = 6) and without (n = 6) carbohydrate. After 5 days of refeeding, fibronectin levels were normalized on the carbohydrate-containing diet, but were still low (82% of normal) on the carbohydrate-free diet. Retinol-binding protein did not fully normalize after 5 days of refeeding. In the two cachectic patients, fibronectin levels prior to total parenteral nutrition were 25 and 75% of normal. Thus, starvation can lower fibronectin levels and this protein is rapidly restored with adequate nutrition.
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PMID:Decreased plasma fibronectin during starvation in man. 642 59

Previously, we showed that retinol inhibited all-trans-retinoic acid (ATRA)-resistant human colon cancer cell invasion via a retinoic acid receptor-independent mechanism. Because phosphatidylinositol 3-kinase (PI3K) regulates cell invasion, the objective of the current study was to determine if retinol affected PI3K activity. Following 24 h of serum starvation, the ATRA resistant human colon cancer cell lines HCT-116 and SW620 were treated with 0, 1, or 10 microM retinol. Thirty minutes of retinol treatment resulted in a significant decrease in PI3K activity in both cell lines. To determine the mechanism by which retinol reduces PI3K activity, the levels and heterodimerization of the regulatory subunit, p85, and the catalytic subunit, p110, of PI3K were examined. Retinol treatment did not alter p85 or p110 protein levels or the heterodimerization of these subunits at any time point examined. To determine if retinol affected the ability of PI3K to phosphorylate the substrate, phosphatidylinositol (PI), PI3K was immunoprecipitated from control cells and incubated with 10 microg PI and increasing concentrations of retinol or 10 microg retinol and increasing concentrations of PI. Retinol decreased PI3K activity in a dose-responsive manner and increased PI suppressed the inhibitory effect of retinol on PI3K activity. Finally, the PI3K inhibitor, LY294002, mimicked the ability of retinol to decrease cell invasion. Computational modeling revealed that retinol may inhibit PI3K activity in a manner similar to that of wortmannin. Thus, a decrease in PI3K activity due to retinol treatment may confer the ability of retinol to inhibit ATRA-resistant colon cancer cell invasion.
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PMID:Retinol decreases phosphatidylinositol 3-kinase activity in colon cancer cells. 1791 8

Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS) activity. Stress and inflammatory signaling pathways--such as Jun-N-terminal Kinase (JNK) signaling--repress IIS, curtailing anabolic processes to promote stress tolerance and extend lifespan. While this interaction constitutes an adaptive response that allows managing energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been found to cause insulin resistance, promoting type II diabetes. Thus, the interaction between JNK and IIS has to be tightly regulated to ensure proper metabolic adaptation to environmental challenges. Here, we identify a new regulatory mechanism by which JNK influences metabolism systemically. We show that JNK signaling is required for metabolic homeostasis in flies and that this function is mediated by the Drosophila Lipocalin family member Neural Lazarillo (NLaz), a homologue of vertebrate Apolipoprotein D (ApoD) and Retinol Binding Protein 4 (RBP4). Lipocalins are emerging as central regulators of peripheral insulin sensitivity and have been implicated in metabolic diseases. NLaz is transcriptionally regulated by JNK signaling and is required for JNK-mediated stress and starvation tolerance. Loss of NLaz function reduces stress resistance and lifespan, while its over-expression represses growth, promotes stress tolerance and extends lifespan--phenotypes that are consistent with reduced IIS activity. Accordingly, we find that NLaz represses IIS activity in larvae and adult flies. Our results show that JNK-NLaz signaling antagonizes IIS and is critical for metabolic adaptation of the organism to environmental challenges. The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis.
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PMID:Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz. 1939 Jun 10

Vitamin A is stored as retinyl esters (REs) in lipid droplets of hepatic stellate cells (HSCs). To date, two different pathways are known to facilitate the breakdown of REs: (i) Hydrolysis of REs by neutral lipases, and (ii) whole lipid droplet degradation in autolysosomes by acid hydrolysis. In this study, we evaluated the contribution of neutral and acid RE hydrolases to the breakdown of REs in human HSCs. (R)-Bromoenol lactone (R-BEL), inhibitor of adipose triglyceride lipase (ATGL) and patatin-like phospholipase domain-containing 3 (PNPLA3), the hormone-sensitive lipase (HSL) inhibitor 76-0079, as well as the serine-hydrolase inhibitor Orlistat reduced neutral RE hydrolase activity of LX-2 cell-lysates between 20 and 50%. Interestingly, in pulse-chase experiments, R-BEL, 76-0079, as well as Orlistat exerted little to no effect on cellular RE breakdown of LX-2 cells as well as primary human HSCs. In contrast, Lalistat2, a specific lysosomal acid lipase (LAL) inhibitor, virtually blunted acid in vitro RE hydrolase activity of LX-2 cells. Accordingly, HSCs isolated from LAL-deficient mice showed RE accumulation and were virtually devoid of acidic RE hydrolase activity. In pulse-chase experiments however, LAL-deficient HSCs, similar to LX-2 cells and primary human HSCs, were not defective in degrading REs. In summary, results demonstrate that ATGL, PNPLA3, and HSL contribute to neutral RE hydrolysis of human HSCs. LAL is the major acid RE hydrolase in HSCs. Yet, LAL is not limiting for RE degradation under serum-starvation. Together, results suggest that RE breakdown of HSCs is facilitated by (a) so far unknown, non-Orlistat inhibitable RE-hydrolase(s).
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PMID:Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation. 3236 Oct 2