Glyceroneogenesis in Adipose Tissue of Fasted, Diabetic and Triamcinolone Treated Rats

Gorin, Erela; Talor, Zvi; Shafrir, Eleazar

doi:10.1111/j.1432-1033.1969.tb00537.x

Cited by 61 publications

(27 citation statements)

References 30 publications

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“…Glyceroneogenesis, a process first described almost 40 years ago (21)(22)(23), has been shown to be up-regulated during periods of decreased glucose availability such as during starvation (2) or feeding of a carbohydrate-free diet (24). We show here, in vivo, that an LC diet increases adipose TG-glycerol n, suggestive of increased glyceroneogenesis.…”

Section: Discussionsupporting

confidence: 57%

Physiologic and Pharmacologic Factors Influencing GlyceroneogenicContribution to Triacylglyceride Glycerol Measured by Mass IsotopomerDistribution Analysis

Chen

Peacock

Samady

et al. 2005

Journal of Biological Chemistry

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An imbalance between triacylglycerol synthesis and breakdown is necessary for the development of obesity. The direct precursor for triacylglycerol biosynthesis is ␣-glycerol phosphate, which can have glycolytic and glyceroneogenic origins. We present a technique for determining the relative glyceroneogenic contribution to triacylglyceride glycerol by labeling the glycerol moiety with 2 H 2 O. The number of hydrogen atoms (n) incorporated from H 2 O into C-H bonds reflects the metabolic source of ␣-glycerol phosphate and can be calculated by combinatorial analysis of the distribution of mass isotopomers in triacylglyceride glycerol. Three physiological settings with potential effects on glyceroneogenesis and glycolysis were studied in rodents. Adipose tissue acylglyceride glycerol in mice fed a low carbohydrate diet had significantly higher values of n than in mice fed a high carbohydrate diet, suggesting an increased contribution from glyceroneogenesis of from 17 to 50% on the low carbohydrate diet. Similarly, mice administered rosiglitazone had a significant relative increase in glyceroneogenesis (from 17 to 53%), indicated by an increase in adipose acylglyceride glycerol n. Fructose infusion in overnight fasted rats rapidly lowered plasma triacylglyceride glycerol n, reflecting a decreased contribution from glyceroneogenesis (from 66 to 34%) presumably because of increased glycolytic input. In conclusion, we demonstrate that the number of C-H atoms derived from cellular H 2 O in triacylglyceride glycerol is an informative indicator of ␣-glycerol phosphate origin and, ultimately, triacylglycerol metabolism. Under certain physiological conditions, glyceroneogenesis can be upregulated in adipose (e.g. low carbohydrate diet) or down-regulated in liver (e.g. fructose infusion). Additionally, stimulation of glyceroneogenesis by rosiglitazone in adipose tissue may be an important factor in the antilipolytic actions of thiazolidinediones.

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Section: Discussionsupporting

confidence: 57%

Physiologic and Pharmacologic Factors Influencing GlyceroneogenicContribution to Triacylglyceride Glycerol Measured by Mass IsotopomerDistribution Analysis

Chen

Peacock

Samady

et al. 2005

Journal of Biological Chemistry

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“…It may be added that the behaviour of adipose tissue enzymes associated with pathways other than lipogenesis is also affected by glucocorticoid treatment, in a manner not necessarily parallel to the liver. The activity of phosphoenolpyruvate carboxylase is suppressed, thus curtailing glyceroneogenesis from non-glucose sources [29,30], whereas that of alanine and aspartate aminotransferases is not changed [29]. On the other hand, the activity of the insulin-sensitive lipoprotein lipase is markedly reduced by glucocorticoids (E. Shafrir and S. Diamant, unpublished).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Activity of Insulin-Dependent Enzymes of Lipogenesis by Glucocorticoids

Diamant

Shafrir

1975

Eur J Biochem

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Administration of triamcinolone or dexamethasone to rats led to a prompt, marked and persistent rise in liver acetyl‐CoA carboxylase activity. The activity of fatty acid synthetase increased to a lesser extent and after a more prolonged glucocorticoid treatment, whereas the changes in that of NADP‐malate dehydrogenase and ATP‐citrate lyase were not appreciable. The overall channeling of [1‐14C]acetyl‐CoA to fatty acids was enhanced. The triamcinolone effect on acetyl‐CoA carboxylase activity appeared to be dependent on the coincident hyperinsulinemia since it was not obtained in alloxan‐diabetic rats, whereas the alanine‐aminotransferase‐inducing effect of this hormone was additive to that of insulin deficiency. In adipose tissue triamcinolone treatment caused a reduction in the activity of all lipogenesis enzymes and blunted their response to insulin administration. The antagonism of glucocorticoids toward insulin, selectively modulating the responses of the insulin‐sensitive enzymes in liver and adipose tissue is discussed. The rise in hepatic lipogenic capacity, through the retention of the ability of insulin to induce acetyl‐CoA carboxylase, may be physiologically important in restraining the ketogenesis from acetyl‐CoA despite the increased fat utilization during glucocorticoid excess.

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“…Glycerol Incorporation in Triacylglycerol- [1,2,[3][4][5][6][7][8][9][10][11][12][13] C]Glycerol (over 99% 13 C) was infused in five normal nonpregnant women after an overnight fast. They were physically healthy and had a negative history of diabetes or other metabolic disorders in their family.…”

Section: Methodsmentioning

confidence: 99%

Glyceroneogenesis and the Source of Glycerol for Hepatic Triacylglycerol Synthesis in Humans

Kalhan

Mahajan

Burkett

et al. 2001

Journal of Biological Chemistry

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Glyceroneogenesis, i.e. the synthesis of the glycerol moiety of triacylglycerol from pyruvate, has been suggested to be quantitatively important in both the liver and adipose tissue during fasting. However, the actual contribution of glyceroneogenesis to triacylglycerol synthesis has not been quantified in vivo in human studies. In the present study we have measured the contribution of glycerol and pyruvate to in vivo synthesis of hepatic triacylglycerol in nonpregnant and pregnant women after an overnight fast. Five nonpregnant women were administered [ 13 C 3 ]glycerol tracer as prime constant rate infusion, and the appearance of tracer in plasma glucose and triacylglycerol was quantified using gas chromatography-mass spectrometry. The contribution of pyruvate to hepatic triacylglycerol was quantified in nonpregnant and pregnant women using the deuterium labeling of body water method. The appearance of [ 2 H] in hydrogens on C 1 and C 3 of triacylglycerol was measured following periodate oxidation of the glycerol isolated from hydrolyzed triacylglycerol. After a 16-h fast, ϳ6.1% of the plasma triacylglycerol pool was derived from plasma glycerol, whereas 10 to 60% was derived from pyruvate in nonpregnant women and pregnant women early in gestation. Our data suggest that glyceroneogenesis from pyruvate is quantitatively a major contributor to plasma triacylglycerol synthesis and may be important for the regulation of very low density lipoprotein triacylglycerol production. Our data also suggest that 3-glycerol phosphate is in rapid equilibrium with the triosephosphate pool, resulting in rapid labeling of the triose pool by the administered tracer glycerol. Because the rate of flux of triosephosphate to glucose during fasting far exceeds that to triacylglycerol, more glycerol ends up in glucose than in triacylglycerol. Alternatively, there may be two distinct pools of 3-glycerol phosphate in the liver, one involved in generating triosephosphate from glycerol and the other involved in glyceride-glycerol synthesis.

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Glyceroneogenesis in Adipose Tissue of Fasted, Diabetic and Triamcinolone Treated Rats

Cited by 61 publications

References 30 publications

Physiologic and Pharmacologic Factors Influencing GlyceroneogenicContribution to Triacylglyceride Glycerol Measured by Mass IsotopomerDistribution Analysis

Physiologic and Pharmacologic Factors Influencing GlyceroneogenicContribution to Triacylglyceride Glycerol Measured by Mass IsotopomerDistribution Analysis

Modulation of the Activity of Insulin-Dependent Enzymes of Lipogenesis by Glucocorticoids

Glyceroneogenesis and the Source of Glycerol for Hepatic Triacylglycerol Synthesis in Humans

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