Uncoupling protein‐2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis‐derived pyruvate utilization

2007 ◽  
Vol 22 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Claire Pecqueur ◽  
Thi Bui ◽  
Chantal Gelly ◽  
Julie Hauchard ◽  
Céline Barbot ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Uncoupling Protein 2

scholarly journals Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation

1997 ◽  
Vol 94 (12) ◽  
pp. 6386-6390 ◽  
Author(s):  
Y.-T. Zhou ◽  
M. Shimabukuro ◽  
K. Koyama ◽  
Y. Lee ◽  
M.-Y. Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Uncoupling Protein 2

scholarly journals Pancreatic Islet Adaptation to Fasting Is Dependent on Peroxisome Proliferator-Activated Receptor α Transcriptional Up-Regulation of Fatty Acid Oxidation

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 375-382 ◽  
Author(s):  
Sandrine Gremlich ◽  
Christopher Nolan ◽  
Raphaël Roduit ◽  
Rémy Burcelin ◽  
Marie-Line Peyot ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pancreatic Islet ◽  
Cellular Response ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Hyperinsulinemic Hypoglycemia ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and liver requires peroxisome proliferator-activated receptor-α (PPARα)-dependent up-regulation of energy metabolism toward fatty acid oxidation (FAO). PPARα null (PPARαKO) mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed that PPARα expression is increased in islets at low glucose. On this basis, we hypothesized that enhanced PPARα expression and FAO, via depletion of lipid-signaling molecule(s) for insulin exocytosis, are also involved in the normal adaptive response of the islet to fasting. Fasted PPARαKO mice compared with wild-type mice had supranormal ip glucose tolerance due to increased plasma insulin levels. Isolated islets from the PPARα null mice had a 44% reduction in FAO, normal glucose use and oxidation, and enhanced glucose-induced insulin secretion. In normal rats, fasting for 24 h increased islet PPARα, carnitine palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and 82%, respectively. The data are consistent with the view that PPARα, via transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that this mechanism is involved in the normal physiological response of the pancreatic islet to fasting such that hypoglycemia is avoided.

scholarly journals The Expression of Uncoupling Protein 3 Coincides With the Fatty Acid Oxidation Type of Metabolism in Adult Murine Heart

2018 ◽  
Vol 9 ◽  
Author(s):  
Karolina E. Hilse ◽  
Anne Rupprecht ◽  
Monika Egerbacher ◽  
Sarah Bardakji ◽  
Lars Zimmermann ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Uncoupling Protein 3

scholarly journals Loss of Fatty Acid Binding Protein 4/aP2 Reduces Macrophage Inflammation Through Activation of SIRT3

2016 ◽  
Vol 30 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Hongliang Xu ◽  
Ann V. Hertzel ◽  
Kaylee A. Steen ◽  
David A. Bernlohr
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Uncoupling Protein ◽  
Monounsaturated Fatty Acids ◽  
Acid Oxidation ◽  
Uncoupling Protein 2 ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Abstract Activation of proinflammatory macrophages plays an important role in the pathogenesis of insulin resistance, type 2 diabetes, and atherosclerosis. Previous work using high fat-fed mice has shown that ablation of the adipocyte fatty acid binding protein (FABP4/aP2) in macrophages leads to an antiinflammatory state both in situ and in vivo, and the mechanism is linked, in part, to increased intracellular monounsaturated fatty acids and the up-regulation of uncoupling protein 2. Here, we show that loss of FABP4/aP2 in macrophages additionally induces sirtuin 3 (SIRT3) expression and that monounsaturated fatty acids (C16:1, C18:1) lead to increased SIRT3 protein expression. Increased expression of SirT3 in FABP4/aP2 null macrophages occurs at the protein level with no change in SirT3 mRNA. When compared with controls, silencing of SIRT3 in Raw246.7 macrophages leads to increased expression of inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase 2. In contrast, loss of SIRT3 in FABP4/aP2-deficient macrophages attenuates the suppressed inflammatory signaling, reduced reactive oxygen species production, lipopolysaccharide-induced mitochondrial dysfunction, and increased fatty acid oxidation. These results suggest that the antiinflammatory phenotype of FABP4/aP2 null mice is mediated by increased intracellular monounsaturated fatty acids leading to the increased expression of both uncoupling protein 2 and SirT3.

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 Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated effect

2002 ◽  
Vol 282 (1) ◽  
pp. E11-E17 ◽  
Author(s):  
Patrick Schrauwen ◽  
Matthijs K. C. Hesselink ◽  
Ilonca Vaartjes ◽  
Esther Kornips ◽  
Wim H. M. Saris ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mrna Expression ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Acute Exercise ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Fasted State ◽  
Glucose Ingestion ◽  
Plasma Ffa

Human and rodent uncoupling protein (UCP)3 mRNA is upregulated after acute exercise. Moreover, exercise increases plasma levels of free fatty acid (FFA), which are also known to upregulate UCP3. We investigated whether the upregulation of UCP3 after exercise is an effect of exercise per se or an effect of FFA levels or substrate oxidation. Seven healthy untrained men [age: 22.7 ± 0.6 yr; body mass index: 23.8 ± 1.0 kg/m2; maximal O2 uptake (V˙o 2 max): 3,852 ± 211 ml/min] exercised at 50% V˙o 2 max for 2 h and then rested for 4 h. Muscle biopsies and blood samples were taken before and immediately after 2 h of exercise and 1 and 4 h in the postexercise period. To modulate plasma FFA levels and fat/glucose oxidation, the experiment was performed two times, one time with glucose ingestion and one time while fasting. UCP3 mRNA and UCP3 protein were determined by RT-competitive PCR and Western blot. In the fasted state, plasma FFA levels significantly increased ( P < 0.0001) during exercise (293 ± 25 vs. 1,050 ± 127 μmol/l), whereas they were unchanged after glucose ingestion (335 ± 54 vs. 392 ± 74 μmol/l). Also, fat oxidation was higher after fasting ( P < 0.05), whereas glucose oxidation was higher after glucose ingestion ( P< 0.05). In the fasted state, UCP3L mRNA expression was increased significantly ( P < 0.05) 4 h after exercise (4.6 ± 1.2 vs. 9.6 ± 3.3 amol/μg RNA). This increase in UCP3L mRNA expression was prevented by glucose ingestion. Acute exercise had no effect on UCP3 protein levels. In conclusion, we found that acute exercise had no direct effect on UCP3 mRNA expression. Abolishing the commonly observed increase in plasma FFA levels and/or fatty acid oxidation during and after exercise prevents the upregulation of UCP3 after acute exercise. Therefore, the previously observed increase in UCP3 expression appears to be an effect of prolonged elevation of plasma FFA levels and/or increased fatty acid oxidation.

scholarly journals Reduced adipose tissue triglyceride synthesis and increased muscle fatty acid oxidation in C5L2 knockout mice

2007 ◽  
Vol 194 (2) ◽  
pp. 293-304 ◽  
Author(s):  
Sabina Paglialunga ◽  
Patrick Schrauwen ◽  
Christian Roy ◽  
Esther Moonen-Kornips ◽  
Huiling Lu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Compensatory Mechanism ◽  
Tissue Mass ◽  
Acyltransferase Activity

Activation of C5L2, a G-protein-coupled receptor, by acylation-stimulating protein/complement C3adesArg (ASP/C3adesArg) has been shown to stimulate triglyceride (TG) synthesis in both mature adipocytes and preadipocytes. ASP is an adipocyte-derived hormone that acts by increasing diacylglycerol acyltransferase activity and glucose transport. ASP-deficient mice (C3KO, precursor protein) are lean, display delayed postprandial TG clearance, increased food intake, and increased energy expenditure. The present study shows that C5L2KO mice on a low fat diet are hyperphagic (~60% increase in total food intake) yet maintain the same body weight and adipose tissue mass as wild-type (WT) controls. However, on a high fat diet, average adipocyte size and adipose tissue TG/DNA content were significantly reduced and postprandial TG clearance was delayed in C5L2KO. Adipose tissue TG synthesis (WT: 47.2 ± 5.6 versus C5L2KO: 7.8 ± 1.8 pmol/μg protein, P < 0.001), TG lipolysis (WT: 227.6 ± 36.4 versus C5L2KO: 45.8 ± 5.0 nmol/μg protein, P < 0.001), and fatty acid re-esterification (WT: 85.3 ± 2.4% versus C5L2KO: 59.5 ± 6.8%, P < 0.001) were significantly reduced in C5L2KO mice. Indirect calorimetry measurements revealed C5L2KO mice have unchanged oxygen consumption levels yet reduced respiratory quotient value, suggesting preferential fatty acid utilization over carbohydrate. In agreement, fatty acid oxidation was elevated in heart and skeletal muscle tissue in C5L2KO mice and skeletal muscle levels of uncoupling protein 3 (425.5 ± 86.3%, P < 0.0001), CD36 (277.6 ± 49.5%, P < 0.05), cytochrome c (252.6 ± 33.9%, P < 0.05), and phospho-acetyl CoA carboxylase (118.4 ± 9.3%, P < 0.05) were significantly increased in C5L2KO mice versus WT (100%). The study shows that in response to reduced TG storage in white adipose tissue, C5L2KO mice have developed a compensatory mechanism of increased muscle fat oxidation.

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