Site of action of putative lipostatic factor: hypothalamic metabolism of parabiotic rats

1989 ◽  
Vol 257 (1) ◽  
pp. R224-R228
Author(s):  
T. R. Kasser ◽  
R. B. Harris ◽  
R. J. Martin
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Caloric Intake ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Gamma Aminobutyric Acid ◽  
Glucose Flux ◽  
Site Of Action ◽  
Net Flux ◽  
Ad Libitum

Studies were conducted to determine whether metabolic adaptation occurred in the hypothalamus of overfed parabiotic rats and their partners to distinguish between the adaptations caused by increased caloric intake and those caused by the production of a "lipostatic factor." The induction of overfed obesity in one parabiotic partner was employed to test the hypothesis that a putative lipostatic factor produced in the obese parabiotic elicited the hypophagic-lipid-mobilizing effect observed in the lean parabiotic via alterations in hypothalamic fatty acid and glucose metabolism. Fatty acid oxidation in the ventrolateral hypothalamus (VLH) of overfed parabiotic rats and their partners was lower than in ad libitum parabiotic rats. Net flux of glucose through the VLH gamma-aminobutyric acid (GABA) shunt was elevated in overfed parabiotic rats compared with the net flux observed in their partners and ad libitum parabiotic rats, the levels being similar in these last two groups. Net flux of glucose through the ventromedial hypothalamic (VMH) pentose shunt in overfed parabiotic rats and their partners was elevated relative to ad libitum parabiotic rats. The putative lipostatic factor may act to regulate energy balance through modification of VLH fatty acid oxidation and/or glucose flux via the VMH pentose shunt.

scholarly journals Regulation of Fatty Acid Oxidation by Twist 1 in the Metabolic Adaptation of T Helper Lymphocytes to Chronic Inflammation

2019 ◽  
Vol 71 (10) ◽  
pp. 1756-1765 ◽  
Author(s):  
Kristyna Hradilkova ◽  
Patrick Maschmeyer ◽  
Kerstin Westendorf ◽  
Heidi Schliemann ◽  
Olena Husak ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chronic Inflammation ◽  
Fatty Acid Oxidation ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
T Helper ◽  
T Helper Lymphocytes ◽  
Twist 1

AMPK and metabolic adaptation by the heart to pressure overload

2007 ◽  
Vol 292 (1) ◽  
pp. H140-H148 ◽  
Author(s):  
Michael F. Allard ◽  
Hannah L. Parsons ◽  
Ramesh Saeedi ◽  
Richard B. Wambolt ◽  
Roger Brownsey
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pressure Overload ◽  
Chain Fatty Acid ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Energy Status ◽  
Long Chain Fatty Acid ◽  
Ampk Activity ◽  
Long Chain

Accelerated glycolysis in hypertrophied hearts may be a compensatory response to reduced energy production from long-chain fatty acid oxidation with 5′-AMP-activated protein kinase (AMPK) functioning as a cellular signal. Therefore, we tested the hypothesis that enhanced fatty acid oxidation improves energy status and normalizes AMPK activity and glycolysis in hypertrophied hearts. Glycolysis, fatty acid oxidation, AMPK activity, and energy status were measured in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague-Dawley rats. Hearts from halothane (3–4%)-anesthetized rats were perfused with KH solution containing either palmitate, a long-chain fatty acid, or palmitate plus octanoate, a medium-chain fatty acid whose oxidation is not impaired in hypertrophied hearts. Compared with control, fatty acid oxidation was lower in hypertrophied hearts perfused with palmitate, whereas it increased to similar values in both groups with octanoate plus palmitate. Glycolysis was accelerated in palmitate-perfused hypertrophied hearts and was normalized in hypertrophied hearts by the addition of octanoate. AMPK activity was increased three- to sixfold with palmitate alone and was reduced to control values by octanoate plus palmitate. Myocardial energy status improved with the addition of octanoate but did not differ between groups. Our findings, particularly the correspondence between glycolysis and AMPK activity, provide support for the view that activation of AMPK is responsible, in part, for the acceleration of glycolysis in cardiac hypertrophy. Additionally, they indicate myocardial AMPK is activated by energy state-independent mechanisms in response to pressure overload, demonstrating AMPK is more than a sensor of the heart's energy status.

Metabolic development in the liver and the implications of the n-3 fatty acid supply

2012 ◽  
Vol 302 (2) ◽  
pp. G250-G259 ◽  
Author(s):  
Elizabeth M. Novak ◽  
Bernd O. Keller ◽  
Sheila M. Innis
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Maternal Diet ◽  
Neonatal Rat ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Flight Mass Spectrometry ◽  
2D Gel ◽  
Hepatic Fatty Acid Oxidation

The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism. Feeding rats 1.5% compared with <0.1% energy 18:3n-3 during gestation led to higher 20:5n-3 and 22:6n-3 in 3-day-old offspring liver, higher serine hydroxymethyltransferase, carnitine palmitoyl transferase, and acyl CoA oxidase and lower pyruvate kinase and stearoyl CoA desaturase gene expression, with higher cholesterol, NADPH and glutathione, and lower glycine ( P < 0.05). Integration of the results suggests that the n-3 fatty acids may be important in facilitating hepatic metabolic adaptation from in utero nutrition to the postnatal high-fat milk diet, by increasing fatty acid oxidation and directing glucose and amino acids to anabolic pathways.

scholarly journals NT-PGC-1α deficiency attenuates high-fat diet-induced obesity by modulating food intake, fecal fat excretion and intestinal fat absorption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jihyun Kim ◽  
Jiyoung Moon ◽  
Chul-Hong Park ◽  
Jisu Lee ◽  
Helia Cheng ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
High Fat ◽  
Male And Female ◽  
Diet Induced Obesity ◽  
Fecal Fat ◽  
Selective Ablation ◽  
Fat Excretion

AbstractTranscriptional coactivator PGC-1α and its splice variant NT-PGC-1α regulate metabolic adaptation by modulating many gene programs. Selective ablation of PGC-1α attenuates diet-induced obesity through enhancing fatty acid oxidation and thermogenesis by upregulation of NT-PGC-1α in brown adipose tissue (BAT). Recently, we have shown that selective ablation of NT-PGC-1α reduces fatty acid oxidation in BAT. Thus, the objective of this study was to test our hypothesis that NT-PGC-1α−/− mice would be more prone to diet-induced obesity. Male and female NT-PGC-1α+/+ (WT) and NT-PGC-1α−/− mice were fed a regular chow or 60% high-fat (HF) diet for 16 weeks. Contrary to our expectations, both male and female NT-PGC-1α−/− mice fed HFD were protected from diet-induced obesity, with more pronounced effects in females. This lean phenotype was primarily driven by reduced dietary fat intake. Intriguingly, HFD-fed female, but not male, NT-PGC-1α−/− mice further exhibited decreased feed efficiency, which was closely associated with increased fecal fat excretion and decreased uptake of fatty acids by the intestinal enterocytes and adipocytes with a concomitant decrease in fatty acid transporter gene expression. Collectively, our results highlight the role for NT-PGC-1α in regulating whole body lipid homeostasis under HFD conditions.

scholarly journals Role of ketone signaling in the hepatic response to fasting

2019 ◽  
Vol 316 (5) ◽  
pp. G623-G631 ◽  
Author(s):  
Caroline E. Geisler ◽  
Susma Ghimire ◽  
Randy L. Bogan ◽  
Benjamin J. Renquist
Keyword(s):  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Transcriptional Level ◽  
Nonalcoholic Fatty Liver ◽  
Fasting Response

Ketosis is a metabolic adaptation to fasting, nonalcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G protein-coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. To understand how β-OH butyrate signaling affects hepatic metabolism, we compared the hepatic fasting response in control and 3-hydroxy-3-methylglutaryl-CoA synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production. To establish that rescue of ketone metabolic/endocrine signaling would restore the normal hepatic fasting response, we gave intraperitoneal injections of β-OH butyrate (5.7 mmol/kg) to HMGCS2 knockdown and control mice every 2 h for the final 9 h of a 16-h fast. In hypoketonemic, HMGCS2 knockdown mice, fasting more robustly increased mRNA expression of uncoupling protein 2 (UCP2), a protein critical for supporting fatty acid oxidation and ketogenesis. In turn, exogenous β-OH butyrate administration to HMGCS2 knockdown mice decreased fasting UCP2 mRNA expression to that observed in control mice. Also supporting feedback at the transcriptional level, β-OH butyrate lowered the fasting-induced expression of HMGCS2 mRNA in control mice. β-OH butyrate also regulates the glycemic response to fasting. The fast-induced fall in serum glucose was absent in HMGCS2 knockdown mice but was restored by β-OH butyrate administration. These data propose that endogenous β-OH butyrate signaling transcriptionally regulates hepatic fatty acid oxidation and ketogenesis, while modulating glucose tolerance. NEW & NOTEWORTHY Ketogenesis regulates whole body glucose metabolism and β-OH butyrate produced by the liver feeds back to inhibit hepatic β-oxidation and ketogenesis during fasting.

scholarly journals Evaluation of malonyl-CoA in the regulation of long-chain fatty acid oxidation in the liver. Evidence for an unidentified regulatory component of the system

1980 ◽  
Vol 192 (3) ◽  
pp. 959-962 ◽  
Author(s):  
J A Ontko ◽  
M L Johns
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Liver Mitochondria ◽  
Chain Fatty Acid ◽  
Molar Ratio ◽  
Acid Oxidation ◽  
Long Chain Fatty Acid ◽  
Malonyl Coa ◽  
Site Of Action ◽  
Long Chain

Palmitate oxidation by liver mitochondria from fed and starved rats exhibited markedly different sensitivities to inhibition by malonyl-CoA. In the mitochondrial system from fed rats, 50% inhibition required 19 muM-malonyl-CoA, whereas the mitochondria from starved rats were by comparison refractory to malonyl-CoA. Inhibition by malonyl-CoA was completely reversed by increasing the molar ratio of fatty acid to albumin. Results indicate that the potential effectiveness of malonyl-CoA as an inhibitor of fatty acid oxidation in the liver is dependent on an unidentified regulatory component of the system. The functional activity of this component is modified by the nutritional state, and its site of action is at the mitochondrial level.

scholarly journals Heat stress decreases metabolic flexibility in skeletal muscle of growing pigs

2018 ◽  
Vol 315 (6) ◽  
pp. R1096-R1106 ◽  
Author(s):  
Lidan Zhao ◽  
Ryan P. McMillan ◽  
Guohao Xie ◽  
Samantha G. L. W. Giridhar ◽  
Lance H. Baumgard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heat Stress ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Feed Intake ◽  
Citrate Synthase ◽  
Growing Pigs ◽  
Acid Oxidation ◽  
Metabolic Flexibility ◽  
Ad Libitum

Heat-stressed pigs experience metabolic alterations, including altered insulin profiles, reduced lipid mobilization, and compromised intestinal integrity. This is bioenergetically distinct from thermal neutral pigs on a similar nutritional plane. To delineate differences in substrate preferences between direct and indirect (via reduced feed intake) heat stress effects, skeletal muscle fuel metabolism was assessed. Pigs (35.3 ± 0.8 kg) were randomly assigned to three treatments: thermal neutral fed ad libitum (TN; 21°C, n = 8), heat stress fed ad libitum (HS; 35°C, n = 8), and TN, pair-fed/HS intake (PF; n = 8) for 7 days. Body temperature (TB) and feed intake (FI) were recorded daily. Longissimus dorsi muscle was biopsied for metabolic assays on days −2, 3, and 7 relative to initiation of environmental treatments. Heat stress increased TBand decreased FI ( P < 0.05). Heat stress inhibited incomplete fatty acid oxidation and glucose oxidation ( P < 0.05). Metabolic flexibility decreased in HS pigs compared with TN and PF controls ( P < 0.05). Both phosphofructokinase and pyruvate dehydrogenase (PDH) activities increased in PF ( P < 0.05); however, TN and HS did not differ. Heat stress inhibited citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activities ( P < 0.05). Heat stress did not alter PDH phosphorylation or carnitine palmitoyltransferase 1 abundance but reduced acetyl-CoA carboxylase 1 (ACC1) protein abundance ( P < 0.05). In conclusion, HS decreased skeletal muscle fatty acid oxidation and metabolic flexibility, likely involving β-HAD and ACC regulation.

Mating behavior is controlled by acute changes in metabolic fuels

2002 ◽  
Vol 282 (3) ◽  
pp. R782-R790 ◽  
Author(s):  
Jennifer L. Temple ◽  
Jill E. Schneider ◽  
Deanna K. Scott ◽  
Alexander Korutz ◽  
Emilie F. Rissman
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Mating Behavior ◽  
Fatty Acid Oxidation ◽  
Food Restriction ◽  
Ketone Bodies ◽  
Acid Oxidation ◽  
Glucose Levels ◽  
Ad Libitum ◽  
Feeding Bout

Mild food restriction for 48 h inhibits mating behavior in female musk shrews ( Suncus murinus). However, mating behavior is restored after a 90-min feeding bout. In this series of experiments, we examined the role of metabolic fuels in this behavioral restoration. First, drugs reported to block glycolysis or fatty acid oxidation were given 2 h before mating. Both treatments inhibited mating in food-restricted females that were refed after treatment. Blood glucose levels were assessed in females that were fed ad libitum, food restricted, or food restricted and refed for 90 min. Food restriction significantly lowered blood glucose compared with ad libitum feeding or food restriction in combination with 90 min of refeeding. However, neither glucose nor fat alone could substitute for food and promote mating behavior in food-restricted females. In addition, analysis of ketone bodies and body composition in females demonstrated low or undetectable levels of these energy substrates. Our data suggest that musk shrews have relatively little stored energy. Therefore, female musk shrews rely on continuous food intake and monitor multiple cues acutely, including glucose availability and fatty acid oxidation. This ensures that mating does not occur when adequate energy is unavailable.

scholarly journals Rapid switch of hepatic fatty acid metabolism from oxidation to esterification during diurnal feeding of meal-fed rats correlates with changes in the properties of acetyl-CoA carboxylase, but not of carnitine palmitoyltransferase I

1993 ◽  
Vol 291 (1) ◽  
pp. 241-246 ◽  
Author(s):  
A M B Moir ◽  
V A Zammit
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Time Course ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Malonyl Coa ◽  
Ad Libitum ◽  
Cpt I

The effects of the ingestion of a meal on the partitioning of hepatic fatty acids between oxidation and esterification were studied in vivo for meal-fed rats. The time course for the reversal of the starved state was extremely rapid and the process was complete within 2 h, in marked contrast with the reversal of the effects of starvation in rats fed ad libitum [A. M. B. Moir and V. A. Zammit (1993) Biochem. J. 289, 49-55]. This rapid reversal occurred in spite of the fact that, in the liver of the meal-fed animals before feeding, a similar degree of partitioning of fatty acids in favour of oxidation was observed as in 24 h-starved rats (previously fed ad libitum). This suggested that the lower degree of ketonaemia observed in meal-fed rats before a meal is not due to the inability of acylcarnitine formation to compete successfully with esterification of fatty acids to the glycerol moiety. Investigation of the possible mechanisms that could contribute towards the rapid switching-off of fatty acid oxidation revealed that this was correlated with a very rapid rise and overshoot in hepatic malonyl-CoA concentration, but not with any change in the activity, or sensitivity to malonyl-CoA, of the mitochondrial overt carnitine palmitoyltransferase (CPT I). The role of these two parameters in the reversal of fasting-induced hepatic fatty acid oxidation was thus the inverse of that observed previously for refed 24 h-starved rats. The rapid increase in [malonyl-CoA] was accompanied by an immediate and complete reversion of the kinetic characteristics (Ka for citrate, expressed/total activity ratio) of acetyl-CoA carboxylase to those found in the post-meal animals, again in contrast with the time course observed in refed 24 h-starved rats [A. M. B. Moir and V. A. Zammit (1990) Biochem. J. 272, 511-517]. The rapidity with which these changes occurred was specific to the partitioning of acyl-CoA; the meal-induced diversion of glycerolipids towards phospholipid synthesis and the acute inhibition of the fractional rate of triacylglycerol secretion occurred with very similar time courses to those observed upon refeeding of 24 h-starved rats. The results confirm the central role played by differences in the dynamics of changes in hepatic malonyl-CoA concentration, and CPT I sensitivity to it, in determining the route through which ingested glucose is converted into hepatic glycogen upon refeeding of starved rats which had previously been meal-fed or fed ad libitum.

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