scholarly journals Blockade of fatty acid oxidation mimics phase II-phase III transition in a fasting bird, the king penguin

2002 ◽  
Vol 283 (1) ◽  
pp. R144-R152 ◽  
Author(s):  
Servane F. Bernard ◽  
Eliane Mioskowski ◽  
René Groscolas
Keyword(s):  
Fatty Acid ◽  
Phase Ii ◽  
Plasma Concentrations ◽  
Fold Increase ◽  
Phase Iii ◽  
Acid Oxidation ◽  
Body Protein ◽  
Nonesterified Fatty Acids ◽  
Protein Sparing

This study tests the hypothesis that the metabolic and endocrine shift characterizing the phase II-phase III transition during prolonged fasting is related to a decrease in fatty acid (FA) oxidation. Changes in plasma concentrations of various metabolites and hormones and in lipolytic fluxes, as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo in spontaneously fasting king penguins in the phase II status (large fat stores, protein sparing) before, during, and after treatment with mercaptoacetate (MA), an inhibitor of FA oxidation. MA induced a 7-fold decrease in plasma β-hydroxybutyrate and a 2- to 2.5-fold increase in plasma nonesterified fatty acids (NEFA), glycerol, and triacylglycerols. MA also stimulated lipolytic fluxes, increasing the rate of appearance of NEFA and glycerol by 60–90%. This stimulation might be partly mediated by a doubling of circulating glucagon, with plasma insulin remaining unchanged. Plasma glucose level was unaffected by MA treatment. Plasma uric acid increased 4-fold, indicating a marked acceleration of body protein breakdown, possibly mediated by a 2.5-fold increase in circulating corticosterone. Strong similarities between these changes and those observed at the phase II-phase III transition in fasting penguins support the view that entrance into phase III, and especially the end of protein sparing, is related to decreased FA oxidation, rather than reduced NEFA availability. MA could be therefore a useful tool for understanding mechanisms underlying the phase II-phase III transition in spontaneously fasting birds and the associated stimulation of feeding behavior.

Lipolytic and metabolic response to glucagon in fasting king penguins: phase II vs. phase III

2003 ◽  
Vol 284 (2) ◽  
pp. R444-R454 ◽  
Author(s):  
Servane F. Bernard ◽  
Marie-Anne Thil ◽  
René Groscolas
Keyword(s):  
Uric Acid ◽  
Plasma Concentration ◽  
Phase Ii ◽  
Metabolic Response ◽  
Plasma Concentrations ◽  
Phase Iii ◽  
Nonesterified Fatty Acids ◽  
Fourfold Increase

This study aims to determine how glucagon intervenes in the regulation of fuel metabolism, especially lipolysis, at two stages of a spontaneous long-term fast characterized by marked differences in lipid and protein availability and/or utilization (phases II and III). Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo in a subantarctic bird (king penguin) before, during, and after a 2-h glucagon infusion. In the two fasting phases, glucagon infusion at a rate of 0.025 μg · kg−1 · min−1induced a three- to fourfold increase in the plasma concentration and in the rate of appearance (Ra) of glycerol and nonesterified fatty acids, the percentage of primary reesterification remaining unchanged. Infusion of glucagon also resulted in a progressive elevation of the plasma concentration of glucose and β-hydroxybutyrate and in a twofold higher insulinemia. These changes were not significantly different between the two phases. The plasma concentrations of triacylglycerols and uric acid were unaffected by glucagon infusion, except for a 40% increase in plasma uric acid in phase II birds. Altogether, these results indicate that glucagon in a long-term fasting bird is highly lipolytic, hyperglycemic, ketogenic, and insulinogenic, these effects, however, being similar in phases II and III. The maintenance of the sensitivity of adipose tissue lipolysis to glucagon could suggest that the major role of the increase in basal glucagonemia observed in phase III is to stimulate gluconeogenesis rather than fatty acid delivery.

Glycerol and NEFA kinetics in long-term fasting king penguins: phase IIversusphase III

2002 ◽  
Vol 205 (17) ◽  
pp. 2745-2754 ◽  
Author(s):  
S. F. Bernard ◽  
C. Fayolle ◽  
J.-P. Robin ◽  
R. Groscolas
Keyword(s):  
Body Mass ◽  
Phase Ii ◽  
Fat Mass ◽  
Feeding Behaviour ◽  
Fold Increase ◽  
Phase Iii ◽  
Protein Catabolism ◽  
Body Protein ◽  
Fat Stores

SUMMARYIn spontaneously fasting birds such as penguins, below a body mass threshold corresponding to the phase II—phase III transition, a metabolic and hormonal shift occurs and feeding behaviour is stimulated(`refeeding signal'). The major aim of this study was to determine whether a decrease in non-esterified fatty acid (NEFA) release from adipose tissue could be a component of this signal. Lipolytic fluxes and primary triacylglycerol:fatty acid (TAG:FA) cycling were determined in vivoin breeding, fasting king penguins (Aptenodytes patagonicus) using continuous infusions of 2-[3H]glycerol and 1-[14C]palmitate under field conditions. In phase II (after approximately 8 days of fasting, large fat stores, body protein spared, N=8), the rate of appearance (Ra) of glycerol and of NEFA were 5.7±0.8 and 10.5±0.4 μmol kg-1min-1, respectively, and the percentage of primary TAG:FA cycling was 41±7%. In phase III (after approximately 25 days of fasting, fat stores reduced by fourfold, increased body protein catabolism, N=9), Ra glycerol kg-1 body mass remained unchanged,whereas Ra glycerol kg-1 fat mass and Ra NEFA kg-1 body mass were increased by 2.8-fold and 1.5-fold, respectively. Increased Ra glycerol kg-1 fat mass was possibly the result of a 3.5-fold increase in circulating glucagon, the increased Ra NEFA kg-1 body mass being attributable to decreased primary TAG:FA cycling. Thus, triggering of the refeeding signal that redirects the behavior of fasting, incubating penguins from incubation towards the search for food after entrance into phase III cannot be ascribed to a reduction in lipolytic fluxes and NEFA availability.

Impact of 1 wk of diabetes on the regulation of myocardial carbohydrate and fatty acid oxidation

1999 ◽  
Vol 277 (2) ◽  
pp. E342-E351 ◽  
Author(s):  
John C. Chatham ◽  
Zhi-Ping Gao ◽  
John R. Forder
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fold Increase ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Acid Oxidation ◽  
Oxidation Rates ◽  
Tissue Extracts ◽  
Isotopomer Analysis ◽  
C Nmr

The aim of this study was to investigate the effect of increasing exogenous palmitate concentration on carbohydrate and palmitate oxidation in hearts from control and 1-wk diabetic rats. Hearts were perfused with glucose, [3-13C]lactate, and [U-13C]palmitate. Substrate oxidation rates were determined by combining13C-NMR glutamate isotopomer analysis of tissue extracts with measurements of oxygen consumption. Carbohydrate oxidation was markedly depressed after diabetes in the presence of low (0.1 mM) but not high (1.0 mM) palmitate concentration. Increasing exogenous palmitate concentration 10-fold resulted in a 7-fold increase in the contribution of palmitate to energy production in controls but only a 30% increase in the diabetic group. Consequently, at 0.1 mM palmitate, the rate of fatty acid oxidation was higher in the diabetic group than in controls; however, at 1.0 mM fatty acid oxidation, it was significantly depressed. Therefore, after 1 wk of diabetes, the major differences in carbohydrate and fatty acid metabolism occur primarily at low rather than high exogenous palmitate concentration.

scholarly journals Specific shifts in the endocannabinoid system in hibernating brown bears

2020 ◽  
Author(s):  
Christian Boyer ◽  
Laura Cussonneau ◽  
Charlotte Brun ◽  
Christiane Deval ◽  
Jean-Paul Pais de Barros ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ursus Arctos ◽  
Mild Hypothermia ◽  
Endocannabinoid System ◽  
Fold Increase ◽  
Physiological Adaptation ◽  
Acid Oxidation ◽  
Brown Bears ◽  
Peripheral Tissues ◽  
Free Ranging

Abstract In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. We hypothesized that specific changes should occur in hibernating brown bears ( Ursus arctos ) due to specific features, including hibernation during half the year at only mild hypothermia while remaining physically inactive without drinking or eating, and the absence of arousal episodes although bears remain sensitive to external disturbances. We explored circulating lipids and the ECS in plasma and metabolically active tissues (muscle and adipose tissue), in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid and a decrease in arachidonic acid. In adipose and muscle tissues of hibernating bears, we found lower concentrations of both two major ligands for endocannabinoid receptors, 2-arachidonoylglycerol (2-AG) and anandamide (AEA). Gene expression was reduced for enzymes that synthesize endocannabinoid compounds, whereas an increase was observed for catabolic enzymes. Reduction in ECS tone may promote mobilization of fat stores and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the maintenance of torpor (reduction in locomotion), while promoting the capacity of bears to sense stimuli from the environment.

scholarly journals Critical Role for Hepatocyte-Specific eNOS in NAFLD and NASH

2021 ◽  
Author(s):  
Rory P. Cunningham ◽  
Mary P. Moore ◽  
Ryan J. Daskek ◽  
Grace M. Meers ◽  
Takamune Takahashi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Critical Role ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid ◽  
Endothelial Nitric Oxide

Regulation of endothelial nitric oxide synthase (eNOS) in hepatocytes may be an important target in nonalcoholic fatty liver disease (NAFLD) development and progression to steatohepatitis (NASH). In this study, we show genetic deletion and viral knockdown of hepatocyte-specific eNOS exacerbated hepatic steatosis and inflammation, decreased hepatic mitochondrial fatty acid oxidation and respiration, increased mitochondrial H<sub>2</sub>O<sub>2</sub> emission, and impaired the hepatic mitophagic (BNIP3 and LC3II) response. Conversely, overexpressing eNOS in hepatocytes in vitro and in vivo increased hepatocyte mitochondrial respiration and attenuated western diet induced NASH. Moreover, patients with elevated NAFLD activity score (histology score of worsening steatosis, hepatocyte ballooning, and inflammation) exhibited reduced hepatic eNOS expression which correlated with reduced hepatic mitochondrial fatty acid oxidation and lower hepatic protein expression of mitophagy protein BNIP3. The current study reveals an important molecular role for hepatocyte-specific eNOS as a key regulator of NAFLD/NASH susceptibility and mitochondrial quality control with direct clinical correlation to patients with NASH.

scholarly journals Pomegranate vinegar feeding enhances fatty acid oxidation: In vitro and in vivo

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
YEOJIN PARK ◽  
Elly Ok ◽  
Hyo Jung Lee ◽  
Ji Yeon Kim ◽  
Mi Kyung Kim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation

scholarly journals Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

2018 ◽  
Vol 46 (1) ◽  
pp. 187-202 ◽  
Author(s):  
Jaume Amengual ◽  
Francisco J. García-Carrizo ◽  
Andrea Arreguín ◽  
Hana Mušinović ◽  
Nuria Granados ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Retinoic Acid ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Kinase Inhibitor ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Protective Effects

Background/Aims: All-trans retinoic acid (ATRA) has protective effects against obesity and metabolic syndrome. We here aimed to gain further insight into the interaction of ATRA with skeletal muscle metabolism and secretory activity as important players in metabolic health. Methods: Cultured murine C2C12 myocytes were used to study direct effects of ATRA on cellular fatty acid oxidation (FAO) rate (using radioactively-labelled palmitate), glucose uptake (using radioactively-labelled 2-deoxy-D-glucose), triacylglycerol levels (by an enzymatic method), and the expression of genes related to FAO and glucose utilization (by RT-real time PCR). We also studied selected myokine production (using ELISA and immunohistochemistry) in ATRA-treated myocytes and intact mice. Results: Exposure of C2C12 myocytes to ATRA led to increased fatty acid consumption and decreased cellular triacylglycerol levels without affecting glucose uptake, and induced the expression of the myokine irisin at the mRNA and secreted protein level in a dose-response manner. ATRA stimulatory effects on FAO-related genes and the Fndc5 gene (encoding irisin) were reproduced by agonists of peroxisome proliferator-activated receptor β/δ and retinoid X receptors, but not of retinoic acid receptors, and were partially blocked by an AMP-dependent protein kinase inhibitor. Circulating irisin levels were increased by 5-fold in ATRA-treated mice, linked to increased Fndc5 transcription in liver and adipose tissues, rather than skeletal muscle. Immunohistochemistry analysis of FNDC5 suggested that ATRA treatment enhances the release of FNDC5/irisin from skeletal muscle and the liver and its accumulation in interscapular brown and inguinal white adipose depots. Conclusion: These results provide new mechanistic insights on how ATRA globally stimulates FAO and enhances irisin secretion, thereby contributing to leaning effects and improved metabolic status.

BAPST. A Combo of Common use drugs as metabolic therapy of cancer—a theoretical proposal.

2021 ◽  
Vol 14 ◽  
Author(s):  
Adriana Romo-Perez ◽  
Guadalupe Dominguez-Gomez ◽  
Alma Chavez-Blanco ◽  
Lucia Taja-Chayeb ◽  
Aurora Gonzalez-Fierro ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mevalonate Pathway ◽  
Classical Model ◽  
Plasma Concentrations ◽  
Metabolic Phenotype ◽  
Cancer Drug ◽  
Acid Oxidation ◽  
Ulcer Disease ◽  
Primary Indication ◽  
Drug Affordability

: Advances in cancer therapy have yet to impact worldwide cancer mortality. Poor cancer drug affordability is one of the factors limiting mortality burden strikes. Up to now, cancer drug repurposing had no meet expectations concerning drug affordability. The three FDA-approved cancer drugs developed under repurposing -all-trans-retinoic acid, arsenic trioxide, and thalidomide- do not differ in price from other drugs developed under the classical model. Though additional factors affect the whole process from inception to commercialization, the repurposing of widely used, commercially available, and cheap drugs may help. This work reviews the concept of the malignant metabolic phenotype and its exploitation by simultaneously blocking key metabolic processes altered in cancer. We elaborate on a combination called BAPST, which stands for the following drugs and pathways they inhibit: Benserazide (glycolysis), Apomorphine (glutaminolysis), Pantoprazole (Fatty-acid synthesis), Simvastatin (mevalonate pathway), and Trimetazidine (Fatty-acid oxidation). Their respective primary indications are: • Parkinson's disease (benserazide and apomorphine). • Peptic ulcer disease (pantoprazole). • Hypercholesterolemia (simvastatin). • Ischemic heart disease (trimetazidine). When used for their primary indication, the literature review on each of these drugs shows they have a good safety profile and lack predicted pharmacokinetic interaction among them. Most importantly, the inhibitory enzymatic concentrations required for inhibiting their cancer targets enzymes are below the plasma concentrations observed when these drugs are used for their primary indication. Based on that, we propose that the regimen BAPTS merits preclinical testing.

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