Glycerokinase in human adipose tissue

Ryall, Rosemary L.; Goldrick, R. B.

doi:10.1007/bf02533346

Cited by 28 publications

(14 citation statements)

References 26 publications

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“…GyK catalyzes direct conversion of glycerol to glycerol-3-phosphate. By comparison with BAT, GyK activity in human WAT is low (28). In human white fat cells, we showed that PGC-1␣ strongly induces GyK gene expression and activity.…”

Section: Discussionmentioning

confidence: 77%

The Transcriptional Coactivator Peroxisome Proliferator–Activated Receptor (PPAR)γ Coactivator-1α and the Nuclear Receptor PPARα Control the Expression of Glycerol Kinase and Metabolism Genes Independently of PPARγ Activation in Human White Adipocytes

et al. 2007

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OBJECTIVE—The purpose of this work was to determine the pattern of genes regulated by peroxisome proliferator–activated receptor (PPAR) γ coactivator 1α (PGC-1α) in human adipocytes and the involvement of PPARα and PPARγ in PGC-1α transcriptional action. RESEARCH DESIGN AND METHODS—Primary cultures of human adipocytes were transduced with a PGC-1α adenovirus and treated with PPARγ and PPARα agonists. Variation in gene expression was assessed using pangenomic microarrays and quantitative RT-PCR. To investigate glycerol kinase (GyK), a target of PGC-1α, we measured enzymatic activity and glycerol incorporation into triglycerides. In vivo studies were performed on wild-type and PPARα−/− mice. The GyK promoter was studied using chromatin immunoprecipitation and promoter reporter gene assays. RESULTS—Among the large number of genes regulated by PGC-1α independently of PPARγ, new targets involved in metabolism included the gene encoding GyK. The induction of GyK by PGC-1α was observed at the levels of mRNA, enzymatic activity, and glycerol incorporation into triglycerides. PPARα was also upregulated by PGC-1α. Its activation led to an increase in GyK expression and activity. PPARα was shown to bind and activate the GyK promoter. Experiments in mice confirmed the role of PGC-1α and PPARα in the regulation of GyK in vivo. CONCLUSIONS—This work uncovers novel pathways regulated by PGC-1α and reveals that PPARα controls gene expression in human white adipocytes. The induction of GyK by PGC-1α and PPARα may promote a futile cycle of triglyceride hydrolysis and fatty acid reesterification.

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Section: Discussionmentioning

confidence: 77%

The Transcriptional Coactivator Peroxisome Proliferator–Activated Receptor (PPAR)γ Coactivator-1α and the Nuclear Receptor PPARα Control the Expression of Glycerol Kinase and Metabolism Genes Independently of PPARγ Activation in Human White Adipocytes

et al. 2007

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“…8 However, it was also considered that TAG accumulation in adipocytes was predominantly attributed to the elevated activity of G3PDH owing to the low activity of glycerokinase, fatty acid synthase and adenosine triphosphate-citrate lyase. 45,46 Currently, G3PDH activity significantly decreased both in psiRNA-AGT1-and psiRNA-AGT2-transfected cells compared with the negative control group (Figure 2). Moreover, G3PDH activity decreased by 22% (psiRNA-AGT1 vs psiRNA-AGT0 (day 6):147.93 ± 9.64 vs 189.74 ± 10.72) or less.…”

Section: Agt Knockdown Inhibits Hpa-v Differentiation Z-w Ye Et Almentioning

confidence: 93%

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Jiang

2009

Int J Obes

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Objective: The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures. Methods: Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation. Results: Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation. Conclusions: Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application.

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“…Both direct and indirect glycerol incorporation rates are provided (see "Materials and Methods" for calculation). Glucose incorporation was measured in additional studies using [6][7][8][9][10][11][12][13][14] C]glucose alone (fed) or together with H]glucose (fasted). Statistical comparisons of incorporation rates of glycerol (direct incorporation only) and glucose ( [6-14 C]glucose-measured rates only) is on a carbon-equivalent basis (glucose incorporation rate ϫ 2).…”

Section: Discussionmentioning

confidence: 99%

“…Glycerol can be converted directly to G3P by glycerol kinase, but this is believed to occur primarily, if not solely, in the liver and kidney because the glycerol kinase activity in these tissues is sufficient to permit large quantities of blood glycerol to be used for gluconeogenesis and TG synthesis. The direct conversion of free glycerol to G3P is thought to be negligible in skeletal muscle and adipose tissue because of their low activities of glycerol kinase (5)(6)(7)(8). A corollary to this supposition is that glycerol generated by the hydrolysis of TG in skeletal muscle quantitatively enters the circulation.…”

mentioning

confidence: 99%

Blood Glycerol Is an Important Precursor for Intramuscular Triacylglycerol Synthesis

Guo

Jensen²

1999

Journal of Biological Chemistry

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The utilization of blood glycerol and glucose as precursors for intramuscular triglyceride synthesis was examined in rats using an intravenous infusion of [2-14 C]glycerol and [6-3 H]glucose or [6-14 C]glucose. In 24-h fasted rats, more glycerol than glucose was incorporated into intramuscular triglyceride glycerol in soleus (69 ؎ 23 versus 4 ؎ 1 nmol/mol triglyceride/h, respectively, p ‫؍‬ 0.02 glycerol versus glucose) and in gastrocnemius (25 ؎ 5 versus 9 ؎ 2 nmol/mol triglyceride/h, respectively, p ‫؍‬ 0.02). Blood glucose was utilized more than blood glycerol for triglyceride glycerol synthesis in quadriceps. In fed rats, the blood glycerol incorporation rates (4 ؎ 2, 8 ؎ 3, and 9 ؎ 3 nmol/mol triglyceride/h) were similar (p > 0.3) to those of glucose (5 ؎ 2, 8 ؎ 2, and 5 ؎ 2 nmol/mol triglyceride/h for quadriceps, gastrocnemius, and soleus muscle, respectively). Glucose incorporation into intramuscular triglycerides was less with [6- 13 C]glycerol) was complete in quadriceps and gastrocnemius, but not soleus, within 2 h after beginning the tracer infusion. We conclude that blood glycerol is a direct and important precursor for muscle triglyceride synthesis in rats, confirming the presence of functionally important amounts of glycerol kinase in skeletal muscle.It is a biochemistry precept that the glycerol moiety of triacylglycerols and phospholipids in non-hepatic mammalian tissues is primarily derived from glucose via glycolysis (1). Dihydroxyacetone phosphate (DHAP), 1 originating from glucose, is reduced to glycerol 3-phosphate (G3P) by the action of glycerophosphate dehydrogenase. G3P then undergoes sequential acylation steps to incorporate three fatty acids to form a triacylglycerol (TG) (2). DHAP can also take a different path (DHAP pathway) via 1-acyldihydroxyacetone phosphate and then 1-acylglycerol 3-phosphate, but this appears to be a quantitatively minor reaction (3, 4). Glycerol can be converted directly to G3P by glycerol kinase, but this is believed to occur primarily, if not solely, in the liver and kidney because the glycerol kinase activity in these tissues is sufficient to permit large quantities of blood glycerol to be used for gluconeogenesis and TG synthesis. The direct conversion of free glycerol to G3P is thought to be negligible in skeletal muscle and adipose tissue because of their low activities of glycerol kinase (5-8). A corollary to this supposition is that glycerol generated by the hydrolysis of TG in skeletal muscle quantitatively enters the circulation. These assumptions form the basis for using systemic glycerol appearance rate, measured by isotope dilution techniques, as a quantitative measure of whole body lipolysis (9, 10).The presence of small but measurable glycerol kinase activity in skeletal muscle of various animal species, including rat (5) and humans (6), raises concerns as to the validity of these assumptions, however. For example, although low in specific activity, skeletal muscle glycerol kinase could be important in the metabolism of circulating glycerol consid...

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Glycerokinase in human adipose tissue

Cited by 28 publications

References 26 publications

The Transcriptional Coactivator Peroxisome Proliferator–Activated Receptor (PPAR)γ Coactivator-1α and the Nuclear Receptor PPARα Control the Expression of Glycerol Kinase and Metabolism Genes Independently of PPARγ Activation in Human White Adipocytes

The Transcriptional Coactivator Peroxisome Proliferator–Activated Receptor (PPAR)γ Coactivator-1α and the Nuclear Receptor PPARα Control the Expression of Glycerol Kinase and Metabolism Genes Independently of PPARγ Activation in Human White Adipocytes

Knockdown of angiotensinogen by shRNA-mediated RNA interference inhibits human visceral preadipocytes differentiation

Blood Glycerol Is an Important Precursor for Intramuscular Triacylglycerol Synthesis

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