Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis

1995 ◽  
Vol 268 (5) ◽  
pp. E956-E964 ◽  
Author(s):  
E. Tozzo ◽  
P. R. Shepherd ◽  
L. Gnudi ◽  
B. B. Kahn
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Transgenic Mice ◽  
Fatty Acid Synthesis ◽  
Glucose Concentration ◽  
Molecular Mechanisms ◽  
Acid Synthesis ◽  
Glut 4 ◽  
Obesity And Diabetes ◽  
The Impact

GLUT-4 expression varies widely among normal humans and those with obesity and diabetes. Using the alpha P2 promoter/enhancer ligated to the human GLUT-4 gene, we created transgenic mice to study the impact of alterations in GLUT-4 expression selectively in adipocytes on glucose homeostasis and body composition. Here we investigated molecular mechanisms for enhanced glucose tolerance and obesity in these mice. [U-14C]glucose incorporation into triglycerides, glyceride-glycerol, glyceride-fatty acids, CO2, and lactate was measured in adipocytes incubated at 3, 0.5, and 3 microM glucose with or without maximally stimulating insulin. In nontransgenic and transgenic mice, the major pathway for glucose metabolism shifts from lipogenesis at tracer glucose concentration to glycolysis at physiological glucose concentration. In transgenic adipocytes incubated at 3 microM glucose, metabolism via all major pathways is enhanced by 8.6- to 38-fold in the absence of insulin and 3- to 13-fold in the presence of insulin. At physiological glucose concentration, constitutive metabolism to triglycerides, CO2, and lactate is two- to threefold greater in transgenic than in nontransgenic adipocytes. De novo fatty acid synthesis is preferentially increased: 31-fold for basal and 21-fold for insulin-stimulated compared with nontransgenic adipocytes. Thus overexpression of GLUT-4 in adipocytes of transgenic mice results in increased glucose metabolism in all major pathways, with differential regulation of the pathways involved in lipogenesis.

scholarly journals Deepure Tea Improves High Fat Diet-Induced Insulin Resistance and Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jing-Na Deng ◽  
Juan Li ◽  
Hong-Na Mu ◽  
Yu-Ying Liu ◽  
Ming-Xia Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthesis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
High Fat ◽  
The Metabolic Syndrome

This study was to explore the protective effects of Deepure tea against insulin resistance and hepatic steatosis and elucidate the potential underlying molecular mechanisms. C57BL/6 mice were fed with a high fat diet (HFD) for 8 weeks to induce the metabolic syndrome. In the Deepure tea group, HFD mice were administrated with Deepure tea at 160 mg/kg/day by gavage for 14 days. The mice in HFD group received water in the same way over the same period. The age-matched C57BL/6 mice fed with standard chow were used as normal control. Compared to the mice in HFD group, mice that received Deepure tea showed significantly reduced plasma insulin and improved insulin sensitivity. Deepure tea increased the expression of insulin receptor substrate 2 (IRS-2), which plays an important role in hepatic insulin signaling pathway. Deepure tea also led to a decrease in hepatic fatty acid synthesis and lipid accumulation, which were mediated by the downregulation of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthesis (FAS), and acetyl-CoA carboxylase (ACC) proteins that are involved in liver lipogenesis. These results suggest that Deepure tea may be effective for protecting against insulin resistance and hepatic steatosis via modulating IRS-2 and downstream signaling SREBP-1c, FAS, and ACC.

scholarly journals Compromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in Defective Protein Lipoylation and Energy Disequilibrium

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47196 ◽  
Author(s):  
Stuart Smith ◽  
Andrzej Witkowski ◽  
Ayesha Moghul ◽  
Yuko Yoshinaga ◽  
Michael Nefedov ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transgenic Mice ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Mitochondrial Fatty Acid

scholarly journals The response of adipocyte glucose metabolism and fatty acid release to adenosine deaminase, insulin and perifusion. Investigation of intermediary metabolism by perifusion

1988 ◽  
Vol 251 (3) ◽  
pp. 733-737
Author(s):  
R D Harper
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Adenosine Deaminase ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Intermediary Metabolism ◽  
Glucose Incorporation ◽  
Fatty Acid Release ◽  
Acid Release

Adipocytes incubated with adenosine deaminase (ADA) showed: (1) increased amounts of fatty acids in the medium; (2) increased glucose incorporation into acylglycerol glycerol; (3) decreased glucose incorporation into acylglycerol fatty acids; (4) a co-ordinate decrease in the sensitivity of lipolysis and glucose incorporation into acylglycerol to insulin; (5) similar effects on glucose incorporations in perifused and normal incubations. The decrease in fatty acid synthesis by perfusion was found to be dependent on the presence of insulin or fatty acids, and independent of the effects of ADA. The significance of the effects of perifusion, ADA and insulin are discussed in relation to effects of fatty acids.

scholarly journals Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Effect of the amount of glucose uptake on the rates of the pentose phosphate cycle and of fatty acid synthesis

1972 ◽  
Vol 128 (5) ◽  
pp. 1089-1096 ◽  
Author(s):  
H. Kather ◽  
M. Rivera ◽  
K. Brand
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Fat Cells ◽  
Pentose Phosphate Cycle ◽  
Wide Range

In order to study the quantitative relationship between fatty acid synthesis and pentose phosphate-cycle activity under different hormonal and dietary conditions affecting the extent of glucose uptake, cells isolated from rat epididymal adipose tissue were incubated in bicarbonate buffer containing [U-14C]-, [1-14C]- or [6-14C]-glucose. From the amount of glucose taken up, the production of lactate and pyruvate, and the incorporation of 14C from differently labelled [14C]glucose into CO2, fatty acids and glyceride glycerol, the rates of glucose metabolism via different pathways and the extent of lipogenesis under various experimental conditions were determined. The contribution of the pentose phosphate-cycle to glucose metabolism under normal conditions was calculated to be 8%. Starvation and re-feeding, and the presence of insulin, caused an enhancement of glucose uptake, pentose phosphate-cycle activity and fatty acid synthesis. Plots of both pentose phosphate-cycle activity and fatty acid synthesis versus glucose uptake revealed that the extent of glucose uptake, over a wide range, determines the rates of fatty acid synthesis and glucose metabolism via the pentose phosphate cycle. A balance of formation and production of nicotinamide nucleotides in the cytoplasm was established. The total amount of cytoplasmic NADH and NADPH formed was only in slight excess over the hydrogen equivalents required for the synthesis of fatty acids, glyceride glycerol and lactate. Except in cells from starved animals, the pentose phosphate cycle was found to provide only about 60% of the NADPH required for fatty acid synthesis. The results are discussed with respect to an overall control of the different metabolic and biosynthetic reactions in the fat-cells by the amount of glucose transported into the cell.

scholarly journals Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Control of pentose phosphate-cycle activity by cellular requirement for reduced nicotinamide adenine dinucleotide phosphate

1972 ◽  
Vol 128 (5) ◽  
pp. 1097-1102 ◽  
Author(s):  
H. Kather ◽  
M. Rivera ◽  
K. Brand
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Synthesis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Fat Cells ◽  
Isolated Fat Cells ◽  
Pentose Phosphate Cycle ◽  
Phenazine Methosulphate

By using inhibitors and stimulators of different metabolic pathways the interdependence of the pentose phosphate cycle and lipogenesis in isolated fat-cells was studied. Rotenone, which is known to inhibit electron transport in the respiratory chain, blocked glucose breakdown at the site of pyruvate dehydrogenase. Consequently, because of the lack of acetyl-CoA, fatty acid synthesis was almost abolished. A concomitant decrease in pentose phosphate-cycle activity was observed. Phenazine methosulphate stimulated pentose phosphate-cycle activity about five- to ten-fold without a considerable effect on fatty acid synthesis. The influence of rotenone on both the pentose phosphate cycle and lipogenesis could be overcome by addition of phenazine methosulphate, indicating that rotenone has no direct effect on these pathways. The decreased rate of the pentose phosphate cycle in the presence of rotenone therefore has to be considered as a consequence of decreased fatty acid synthesis. The rate of glucose catabolism via the pentose phosphate cycle in adipocytes appears to be determined by the requirement of NADPH for lipogenesis. Treatment of cells with 6-aminonicotinamide caused an accumulation of 6-phosphogluconate, indicating an inhibition of 6-phosphogluconate dehydrogenase. The rate of glucose metabolism via the pentose phosphate cycle as well as the rate of fatty acid synthesis, however, was not affected by 6-aminonicotinamide treatment and could still be stimulated by addition of insulin. Since even in cells from starved animals, in which the pentose phosphate-cycle activity is extremely low, no accumulation of 6-phosphogluconate was observed, it is concluded that the control of this pathway is achieved by the rate of regeneration of NADP at the site of glucose 6-phosphate dehydrogenase.

The impact of medicinal plant Ocimum minimum L. on fatty acid synthesis process in breast cancer cells

Biologia ◽  
2022 ◽  
Author(s):  
Jovana V. Jovankić ◽  
Danijela M. Cvetković ◽  
Milena G. Milutinović ◽  
Danijela D. Nikodijević ◽  
Aleksandra G. Nikezić ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Breast Cancer Cells ◽  
Acid Synthesis ◽  
Synthesis Process ◽  
The Impact

scholarly journals Effects of glucose metabolism on the regulation of genes of fatty acid synthesis and triglyceride secretion in the liver

2007 ◽  
Vol 48 (7) ◽  
pp. 1499-1510 ◽  
Author(s):  
Núria Morral ◽  
Howard J. Edenberg ◽  
Scott R. Witting ◽  
Jennifer Altomonte ◽  
Tearina Chu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Triglyceride Secretion
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