Glucose handling by hepatocytes from obese Zucker rats

1991 ◽  
Vol 11 (5) ◽  
pp. 285-292 ◽  
Author(s):  
Neus Carbó ◽  
Francisco J. López-Soriano ◽  
Josep M. Argilés
Keyword(s):  
Fatty Acids ◽  
Lipid Synthesis ◽  
Pentose Phosphate ◽  
High Rate ◽  
Zucker Rats ◽  
Esterified Fatty Acids ◽  
Obese Zucker Rats ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Phenazine Methosulphate ◽  
Substrate Concentrations

Hepatocytes isolated from obese Zucker rats showed a significantly higher rate of both [U-14C]glucose and [U-14C]lactate incorporation into [14C]lipid than those from their lean counterparts. This was associated with a marked increase in the lipogenic rate measured by the incorporation of3H2O into the cell esterified fatty acids. Although there were no changes in the incorporation of the tracer into either [14C]glycogen or14CO2, the [14C] total uptake was significantly higher in the obese animals. The high rate of [14C]lipid synthesis from glucose was observed both at 15 and 30 mM substrate concentrations and was linked to an enhanced uptake of the tracer into the cell as measured using the decarboxilation of [1-14C]glucose in the presence of phenazine methosulphate. The presence of insulin in the incubation medium had no effect on the uptake of glucose by the liver cells. However, the large uptake of glucose by the hepatocytes from the obese animals was not related to an enhanced rate of transport as measured using 3-O-methyl[U-14C]glucose. The activity of glucose-6-phosphate dehydrogenase together with a higher [1-14C]glucose/[U-14C]glucose descarboxylation ratio indicate a predominant very active pentose phosphate pathway which may be responsible for the enhanced glucose uptake observed in the hepatocytes from the obese animals.

Feedback modeling of non-esterified fatty acids in obese Zucker rats after nicotinic acid infusions

2013 ◽  
Vol 40 (6) ◽  
pp. 623-638 ◽  
Author(s):  
Christine Ahlström ◽  
Tobias Kroon ◽  
Lambertus A. Peletier ◽  
Johan Gabrielsson
Keyword(s):  
Fatty Acids ◽  
Nicotinic Acid ◽  
Zucker Rats ◽  
Esterified Fatty Acids ◽  
Obese Zucker Rats

scholarly journals Endocannabinoids May Mediate the Ability of (n-3) Fatty Acids to Reduce Ectopic Fat and Inflammatory Mediators in Obese Zucker Rats

2009 ◽  
Vol 139 (8) ◽  
pp. 1495-1501 ◽  
Author(s):  
Barbara Batetta ◽  
Mikko Griinari ◽  
Gianfranca Carta ◽  
Elisabetta Murru ◽  
Alessia Ligresti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Inflammatory Mediators ◽  
Zucker Rats ◽  
Ectopic Fat ◽  
Obese Zucker Rats

scholarly journals Serum adipokine profile and fatty acid composition of adipose tissues are affected by conjugated linoleic acid and saturated fat diets in obese Zucker rats

2009 ◽  
Vol 103 (6) ◽  
pp. 869-878 ◽  
Author(s):  
Susana V. Martins ◽  
Paula A. Lopes ◽  
Cristina M. Alfaia ◽  
Pedro O. Rodrigues ◽  
Susana P. Alves ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Saturated Fat ◽  
Zucker Rats ◽  
Adipose Tissues ◽  
Obese Zucker Rats ◽  
Fat Diets ◽  
Pai 1

Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2 % cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1 % of a mixture (1:1) ofcis-9,trans-11 andtrans-10,cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-α and IL-1β. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that thetrans-10,cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition.

Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased by polyunsaturated fatty acids

1996 ◽  
Vol 271 (1) ◽  
pp. E44-E49 ◽  
Author(s):  
B. H. Jones ◽  
M. A. Maher ◽  
W. J. Banz ◽  
M. B. Zemel ◽  
J. Whelan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Polyunsaturated Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Corn Oil ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Obese Zucker Rats ◽  
Stearoyl Coa Desaturase

Stearoyl-CoA desaturase (SCD) is a key regulatory enzyme in the synthesis of unsaturated fatty acids. Although regulation of hepatic SCD by obesity and polyunsaturated fatty acids (PUFA) has been well investigated, no studies have addressed whether similar regulation occurs in adipose tissue. We addressed these questions by feeding control (12% corn oil) and high-PUFA (48% corn oil) diets to lean and obese Zucker rats and analyzing SCD mRNA levels in adipose tissue and liver. We report that SCD mRNA content was dramatically elevated in adipose tissue of obese vs. lean rats on both diets and was significantly decreased by PUFA in both genotypes. Interestingly, we demonstrate that SCD expression was directly downregulated in a dose dependent manner by PUFA in 3T3-L1 adipocytes. We conclude that 1) obese Zucker rats overexpress the SCD gene in both liver and adipose tissue and 2) PUFA directly suppress SCD expression in adipocytes. Further studies will elucidate the mechanisms responsible for obesity- and PUFA-mediated regulation of SCD in adipose cells.

scholarly journals Pentose phosphate pathway activity parallels lipogenesis but not antioxidant processes in rat liver

2018 ◽  
Vol 314 (6) ◽  
pp. E543-E551 ◽  
Author(s):  
Eunsook S. Jin ◽  
Min Hee Lee ◽  
Rebecca E. Murphy ◽  
Craig R. Malloy
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Pentose Phosphate Pathway ◽  
Antioxidant Defense ◽  
Pentose Phosphate ◽  
Zucker Rats ◽  
Pathway Activity ◽  
Zucker Diabetic Fatty Rats ◽  
Obese Zucker Rats ◽  
Biomarkers Of Oxidative Stress

The pentose phosphate pathway (PPP) is widely assumed to play a key role in both reductive biosynthesis and protection from oxidative stress because it is the major source of NADPH. However, little is known about the activity of the PPP in fatty liver, which is characterized by both oxidative stress and lipogenesis. This study was designed to test whether the PPP is active in parallel with lipogenesis and antioxidant processes in the fatty liver of whole animals. Eight- and 16-wk-old obese Zucker diabetic fatty rats and their lean littermates received [U-13C3]glycerol, and 13C labeling patterns of glucose and triglycerides were analyzed for the assessment of hepatic PPP activity and the potentially related processes simultaneously. Oxidative stress, antioxidant activity, and NADPH-producing enzymes in the liver were further examined. Both PPP activity and lipogenesis increased in the fatty liver of young obese Zucker rats but decreased together in older obese Zucker rats. As expected, lipid peroxidation measured by malondialdehyde increased in the fatty liver of obese Zucker rats at both ages. However, evidence for antioxidant processes such as [glutathione] or activities of glutathione reductase, glutathione peroxidase, and catalase was not altered. Hepatic PPP activity paralleled lipogenesis but was dissociated from biomarkers of oxidative stress or antioxidant processes. In summary, NADPH from the PPP was presumably consumed for reductive biosynthesis rather than antioxidant defense in the fatty liver.

scholarly journals c-MYC Triggers Lipid Remodelling During Early Somatic Cell Reprogramming to Pluripotency

2021 ◽  
Author(s):  
Javier Prieto ◽  
Juan Carlos García-Cañaveras ◽  
Marian León ◽  
Ramón Sendra ◽  
Xavier Ponsoda ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Somatic Cell ◽  
Pentose Phosphate Pathway ◽  
Aerobic Glycolysis ◽  
Pentose Phosphate ◽  
High Rate ◽  
Cell Reprogramming ◽  
Acyl Chains

AbstractMetabolic rewiring and mitochondrial dynamics remodelling are hallmarks of cell reprogramming, but the roles of the reprogramming factors in these changes are not fully understood. Here we show that c-MYC induces biosynthesis of fatty acids and increases the rate of pentose phosphate pathway. Time-course profiling of fatty acids and complex lipids during cell reprogramming using lipidomics revealed a profound remodelling of the lipid content, as well as the saturation and length of their acyl chains, in a c-MYC-dependent manner. Pluripotent cells displayed abundant cardiolipins and scarce phosphatidylcholines, with a prevalence of monounsaturated acyl chains. Cells undergoing cell reprogramming showed an increase in mitochondrial membrane potential that paralleled that of mitochondrial-specific cardiolipins. We conclude that c-MYC controls the rewiring of somatic cell metabolism early in cell reprogramming by orchestrating cell proliferation, synthesis of macromolecular components and lipid remodelling, all necessary processes for a successful phenotypic transition to pluripotency. Graphical Abstract c-MYC promotes anabolic metabolism, mitochondrial fitness and lipid remodelling early in cell reprogramming. A high rate of aerobic glycolysis is crucial to provide intermediaries for biosynthetic pathways. To ensure the availability of nucleotides, amino acids and lipids for cell proliferation, cells must provide with a constant flux of the elemental building blocks for macromolecule assembly and fulfil the anabolic demands to reach the critical cellular mass levels to satisfactorily undergo cell division. A high rate of aerobic glycolysis is induced by c-MYC, increasing the amounts of intracellular Glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), and glyceraldehyde-3-phosphate (GA3P), which can all enter pentose phosphate pathway (PPP) to produce Ribose-5-Phosphate (R5P) and NADPH, which are necessary for the biosynthesis of biomolecules such as proteins, nucleic acids, or lipids. C-MYC-dependent activation of glucose-6-phosphate dehydrogenase (G6PD) may play a critical role in the shunting of G6P to PPP and generation of NADPH. High glycolytic flux increases the amounts of dihydroxyacetone phosphate (DHAP), which is crucial for biosynthesis of phospholipids and triacylglycerols, and pyruvate (Pyr), which can be converted to citrate (Cit) in the mitochondria and enter the biosynthesis of fatty acids (FA). During cell reprogramming, c-MYC-dependent lipid remodelling leads to Polyunsaturated Fatty Acid (PUFA) downregulation and Monounsaturated Fatty Acid (MUFA) upregulation, which may play critical roles in cytoarchitectural remodelling of cell membrane or non-canonical autophagy, respectively. Cardiolipin (pink dots) rise early in cell reprogramming correlates with an increase in mitochondrial fitness, suggesting that c-MYC may restore proper levels of cardiolipins and antioxidant proteins, such as UCP2, to guarantee an optimal mitochondrial function while upholding ROS levels, reinforcing the idea of cell rejuvenation early in cell reprogramming.

Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats

Metabolism ◽  
1981 ◽  
Vol 30 (11) ◽  
pp. 1135-1142 ◽  
Author(s):  
Joseph Triscari ◽  
M.R.C. Greenwood ◽  
Ann C. Sullivan
Keyword(s):  
Lipid Synthesis ◽  
Zucker Rats ◽  
Obese Zucker Rats

scholarly journals Regulation of the oxidative phase of the pentose phosphate cycle in mussels

1978 ◽  
Vol 170 (3) ◽  
pp. 577-585 ◽  
Author(s):  
S Rodriguez-Segade ◽  
M Freire ◽  
A Carrion
Keyword(s):  
Inorganic Ions ◽  
Pentose Phosphate ◽  
Oxidized Glutathione ◽  
Phosphogluconate Dehydrogenase ◽  
Pentose Phosphate Cycle ◽  
Intracellular Concentrations ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Substrate Concentrations

1. The mechanisms that control the oxidative phase of the pentose phosphate cycle in mussel hepatopancreas were investigated. 2. The effects of GSSG (oxidized glutathione) on the inhibition of glucose 6-phosphate dehydrogenase by NADPH [Eggleston & Krebs (1974) Biochem. J. 138, 425-435] extend to 6-phosphogluconate dehydrogenase. 3. The effect of GSSG on both enzymes increases as the [NADP+1]/[NADPH] ratio decreases; greater percentage deinhibition always was obtained for 6-phosphogluconate dehydrogenase. 4. Increasing concentration of GSSG increased the percentage deinhibition. This effect is more pronounced with 6-phosphogluconate dehydrogenase. 5. We confirmed the apparent imbalance between the activities of the two enzymes [sapag-Hagar, Lagunas & Sols (1973) Biochem. Biophys. Res. Commun, 50, 179-185] in the presence of 10mM-Mg2+. 6. The imbalance practically disappears when the substrate concentrations are less than saturating and Mg2+ approaches physiological concentrations. 7. The addition of GSSG at physiological concentrations allows the activities of both enzymes to be measured at high [NADPH]/[NADP+] ratios ratios and the co-operative action of GSSG and Mg2+ on the imbalance between the two enzymes to be verifed. 8. The control of the activity of the two enzymes of the pentose cycle could be carried out by deinhibition of the two dehydrogenases and by the intracellular concentrations of substrates and inorganic ions.

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