scholarly journals Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes

2016 ◽  
Vol 58 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Zehra Irshad ◽  
Federica Dimitri ◽  
Mark Christian ◽  
Victor A. Zammit
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Diacylglycerol Acyltransferase ◽  
Acid Oxidation ◽  
Brown Adipocytes

Abstract 344: FNDC5, a PGC1-a-Dependent Myokine, Increases Glucose Utilization and Fatty-Acid Oxidation by AMPK Signaling Pathway

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ling Tao ◽  
Yi Liu ◽  
Chao Xin ◽  
Weidong Huang ◽  
Lijian Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
C2c12 Cells ◽  
Time Dependent ◽  
Acid Oxidation ◽  
Ampk Signaling

FNDC5 is a hormone secreted by myocytes that could reduce obesity and insulin resistance, However, the exact effect of FNDC5 on glucose and lipid metabolism remain poorly identified; More importantly, the signaling pathways that mediate the metabolic effects of FNDC5 is completely unknown. Here we showed that FNDC5 stimulates β-oxidation and glucose uptake in C2C12 cells in a dose- and time-dependent fashion in vitro (n=8, all P<0.01). In vivo study revealed that FNDC5 also enhanced glucose tolerance in diabetic mice and increased the glucose uptake evidenced by increased [18F] FDG accumulation in hearts by PET scan (n=6, all P<0.05). FNDC5 decreased the expression of gluconeogenesis related molecules (PEPCK and G6Pase) and increased the phosphorylation of ACC, a key modulator of fatty-acid oxidation, both in hepatocytes and C2C12 cells (n=3, all P<0.05). In parallel with its stimulation of β-oxidation and glucose uptake, FNDC5 increased the phosphorylation of AMPK both in hepatocytes and C2C12 cells in a dose- and time-dependent fashion in vitro and in vivo. More importantly, the β-oxidation and glucose uptake, the expression of PEPCK and G6Pase and the phosphorylation of ACC induced by FNDC5 were attenuated by AMPK inhibitor in hepatocytes and C2C12 cells (P<0.05). Most importantly, the FNDC5 induced glucose uptake and phosphorylation of ACC were attenuated in AMPK-DN mice (n=6, all P<0.05). The glucose-lowering effect of FNDC5 in diabetic mice was also attenuated by AMPK inhibitor. Our data presents the direct evidence that FNDC5 stimulates glucose utilization and fatty-acid oxidation by AMPK signaling pathway, suggesting that FNDC5 be a novel pharmacological approach for type 2 diabetes.

Effects of blockade of fatty acid oxidation on whole body and tissue-specific glucose metabolism in rats

1993 ◽  
Vol 265 (4) ◽  
pp. E592-E600 ◽  
Author(s):  
A. B. Jenkins ◽  
L. H. Storlien ◽  
G. J. Cooney ◽  
G. S. Denyer ◽  
I. D. Caterson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Oxidation ◽  
Pyruvate Dehydrogenase ◽  
Glucose Utilization ◽  
Whole Body ◽  
Acid Oxidation ◽  
Tissue Specific ◽  
Glucose Output

We examined the effect of the long-chain fatty acid oxidation blocker methyl palmoxirate (methyl 2-tetradecyloxiranecarboxylate, McN-3716) on glucose metabolism in conscious rats. Fasted animals [5 h with or without hyperinsulinemia (100 mU/l) and 24 h] received methyl palmoxirate (30 or 100 mg/kg body wt po) or vehicle 30 min before a euglycemic glucose clamp. Whole body and tissue-specific glucose metabolism were calculated from 2-deoxy-[3H]-glucose kinetics and accumulation. Oxidative metabolism was assessed by respiratory gas exchange in 24-h fasted animals. Pyruvate dehydrogenase complex activation was determined in selected tissues. Methyl palmoxirate suppressed whole body lipid oxidation by 40-50% in 24-h fasted animals, whereas carbohydrate oxidation was stimulated 8- to 10-fold. Whole body glucose utilization was not significantly affected by methyl palmoxirate under any conditions; hepatic glucose output was suppressed only in the predominantly gluconeogenic 24-h fasted animals. Methyl palmoxirate stimulated glucose uptake in heart in 24-h fasted animals [15 +/- 5 vs. 220 +/- 28 (SE) mumol x 100 g-1 x min-1], with smaller effects in 5-h fasted animals with or without hyperinsulinemia. Methyl palmoxirate induced significant activation of pyruvate dehydrogenase in heart in the basal state, but not during hyperinsulinemia. In skeletal muscles, methyl palmoxirate suppressed glucose utilization in the basal state but had no effect during hyperinsulinemia; pyruvate dehydrogenase activation in skeletal muscle was not affected by methyl palmoxirate under any conditions. The responses in skeletal muscle are consistent with the operation of a mechanism similar to the Pasteur effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts

1993 ◽  
Vol 265 (5) ◽  
pp. H1614-H1622
Author(s):  
A. J. Liedtke ◽  
B. Renstrom ◽  
S. H. Nellis ◽  
R. Subramanian ◽  
G. Woldegiorgis
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Myocardial Metabolism ◽  
Respiratory Control ◽  
Acid Oxidation ◽  
Membrane Transporter ◽  
Exogenous Glucose ◽  
14Co2 Production ◽  
Metabolic Behavior

The purpose of these studies was to evaluate metabolic behavior in a 4-day reperfusion model in pigs after induction of subendocardial infarction. Two groups of swine [sham and intervention (Int) groups, n = 7) and 10 hearts per group, respectively] were prepared comparably with two surgical procedures separated over 4 days. In the Int group at the time of the first surgery, coronary flow in the left anterior descending (LAD) circulation was partially restricted (by 60%) for 60 min and was then reperfused. LAD myocardium at the time of the second surgery in both groups was extracorporeally perfused aerobically (5.9 +/- 0.2 ml.min-1.g dry wt-1) for 60 min and infused by equilibrium labeling with [U-14C]-palmitate and [5-3H]glucose to estimate fatty acid oxidation and exogenous glucose utilization. During extracorporeal perfusion, regional myocardial shortening and oxygen consumption were comparable between groups despite a marginal impairment in ATP resynthesis by mitochondria (26% decrease, P < 0.071) in Int hearts and a significant decline in mitochondrial respiration (45% decrease in respiratory control rate, P < 0.008; and 41% decrease in state 3 respiration, P < 0.032) as compared with sham hearts. Fatty acid oxidation described by 14CO2 production was 34.00 +/- 4.72 mumol.h-1.g dry wt-1 (averaged from 30-60 min of perfusion) in sham hearts but was decreased (by 48%, P < 0.004) in Int hearts. This reduction in fatty acid utilization may in part be explained by declines in the observed activity of the mitochondrial membrane transporter enzyme, carnitine palmitoyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats

2013 ◽  
Vol 54 (5) ◽  
pp. 1369-1384 ◽  
Author(s):  
Gudrun Schober ◽  
Myrtha Arnold ◽  
Susan Birtles ◽  
Linda K. Buckett ◽  
Gustavo Pacheco-López ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Energy Intake ◽  
Diacylglycerol Acyltransferase ◽  
Acid Oxidation

scholarly journals The effects of inhibition of fatty acid oxidation in suckling newborn rats

1977 ◽  
Vol 166 (3) ◽  
pp. 631-634 ◽  
Author(s):  
J P Pégorier ◽  
P Ferré ◽  
J Girard
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Ketone Bodies ◽  
Normal Blood ◽  
Acid Oxidation ◽  
Newborn Rats ◽  
Normal Blood Glucose ◽  
Blood Ketone Bodies

Inhibition of fatty acid oxidation with pent-4-enoate in suckling newborn rats caused a fall in blood [glucose] and blood [ketone bodies] and inhibition of gluconeogenesis from lactate. Glucose utilization was not increased in newborn rats injected with pent-4-enoate. Active fatty acid oxidation appears to be essential to support gluconeogenesis and to maintain normal blood [glucose] in suckling newborn rats.

Fatty acid oxidation and glucose utilization interact to control food intake in rats

1986 ◽  
Vol 251 (5) ◽  
pp. R840-R845 ◽  
Author(s):  
M. I. Friedman ◽  
M. G. Tordoff
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Combined Treatment ◽  
Fat Metabolism ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Control Food ◽  
Control Food Intake

To determine whether glucose and fat metabolism interact to control food intake, rats were administered 2-deoxyglucose (2-DG), which inhibits glucose utilization, and methyl palmoxirate (MP), which inhibits fatty acid oxidation. Combined treatment with 2-DG and MP increased food intake in a synergistic fashion. This synergistic effect was observed even at doses of the two agents that alone did not increase food intake, and it was expressed by either an initiation of eating or a prolonged bout of eating, depending on the testing conditions. Metabolic measures of circulating substrates, liver glycogen, and gastric contents confirmed that the drugs had their intended metabolic effects and revealed no evidence that one drug enhanced the direct metabolic action of the other. The results provide direct evidence that glucose and fat metabolism exert a coordinated control over feeding behavior and suggest the existence of a common integrative mechanism in that control.

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