Phosphatidate Phosphohydrolase Activity in the Liver
David N. Brindley, John R. Sabine in Phosphatidate Phosphohydrolase, 2017
The administration of l-thyroxine to rats for 5 days increased the ability of liver homogenates to synthesize diacylglycerols and triacylglycerols from glycerol phosphate but without significantly increasing the activity of glycerol phosphate acyltransferase.73 These results indicate an increased activity of phosphatidate phosphohydrolase. This conclusion was later confirmed in rats that had been injected for 5 or 7 days with l-thyroxine when the phosphohydrolase activity was expressed per milligram of soluble protein8 or per gram wet weight,31 respectively. However, there was no significant increase in the phosphohydrolase activity when the results were expressed per total liver. The long-term treatment of rats of l-thyroxine also stimulated the synthesis of triacylglycerols as measured in vivo from intraportally injected [3H]-glycerol and [14C]-palmitate.8 This may be part of a general stimulation of metabolism. The increase in triacylglycerol synthesis was also accompanied by a decrease in the accumulation of 3H and 14C in diacylglycerol.8 This possibly indicates a stimulation in diacylglycerol acyltransferase activity as suggested from earlier work.74
Increasing the Sensitivity of Adipocytes and Skeletal Muscle Cells to Insulin
Christophe Wiart in Medicinal Plants in Asia for Metabolic Syndrome, 2017
In adipocytes, absorbed fatty acids from very low density lipoproteins or chylomicrons are re-esterified to glycerol via a reaction involving glycerol-3-phosphate acyltransferase, 1-acylglycerol-3-phosphate acyl transferase, phosphatidate phosphohydrolase, and diacylglycerol acyltransferase-1.173 Diacylglycerol acyltransferase-1 in adipocytes catalyzes the acylation of 1,2-diacylglycerol into triglyceride which is a rate limiting step in triglyceride synthesis in adipose tissues.173 Aphadilactone A and aphadilactone C (Figure 4.8) isolated from the leaves of Aphanamixis grandifolia Bl. inhibited diacylglycerol acyltransferase-1 activity by 2 5.5% and 85.9% at 10 μM in vitro.174
Molecular sport nutrition
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
In addition to the enhanced ability to transport fatty acids into skeletal muscle and across the mitochondrial membrane, fat adaptation also increases the ability to store lipids within the muscle as IMTGs. In relation to timing, it is noteworthy that as little as two days of a high-fat diet has been shown to increase resting IMTG concentrations by 36% in endurance-trained cyclists (28). The increase in IMTG content appears to provide the main substrate responsible for the elevated rates of fat oxidation observed following fat adaptation, as inhibiting adipose tissue lipolysis (via the administration of a pharmacological lipolysis inhibitor, acipimox) does not significantly impact this response (28). The increase in IMTG concentrations following fat adaptation suggest an increase in lipid synthesis (the process of creating new lipids) above that of lipid degradation (the breakdown of lipids into their fatty acid constituents) during the rest periods between daily workouts. Whilst the increase in fatty acid transporters clearly plays a role in the ability to uptake fatty acids into skeletal muscle, the storage of fatty acids as triglycerides requires the attachment of fatty acids to the glycerol backbone. As this process requires the activity the enzymes glycerol-3-phosphate acyltransferase (GPAT) and diacylglycerol acyltransferase (DGAT) it seems plausible to consider that both enzymes may be upregulated in response to fat adaptation. Unfortunately, human studies to support this theory are currently lacking, although rodent studies have provided preliminary data that demonstrate increases in the mRNA expression of DGAT1 in skeletal muscle and the activity of GPAT within the liver, suggesting that both proteins are sensitive to alterations in fatty acid availability (29, 30). Clearly, more evidence is needed before definitive conclusions can be made in relation to how fat adaptation influences enzymes involved in lipid storage.
Recent developments in pharmacotherapy for hypertriglyceridemia: what’s the current state of the art?
Published in Expert Opinion on Pharmacotherapy, 2020
Matilda Florentin, Michael S Kostapanos, Panagiotis Anagnostis, George Liamis
Acyl-coA: diacylglycerol acyltransferase (DGAT)-1 is an enzyme required for TG synthesis from absorbed dietary fat. In particular, it catalyzes the final step of TG biosynthesis and is abundant in enterocytes of the small intestine and adipose tissue [125]. Its inhibition has been suggested as an attractive target to reduce postprandial TG levels, especially in patients with FCS. Two molecules have been developed for this purpose, pradigastat (Novartis, Switzerland) and AZD7687 (AstraZeneca, UK). The latter compound has been associated with severe gastrointestinal adverse effects, which have suspended its use [126]. Early data emerged from DGAT-1 knockout mice, showing a reduction in postprandial hypertriglyceridemia, obesity and insulin resistance compared with the conventional type [127].
Aberrant lipid metabolism as a therapeutic target in liver cancer
Published in Expert Opinion on Therapeutic Targets, 2019
Evans D. Pope, Erinmarie O. Kimbrough, Lalitha Padmanabha Vemireddy, Phani Keerthi Surapaneni, John A. Copland, Kabir Mody
Once these FAs have been produced, they are prepared for storage. In the liver, glucose is converted into glyceraldehyde 3-phosphate (G3P) via glycolysis [12]. G3P is bound with activated FAs via acyltransferases (AT) to form lysophosphatidic acid. An additional activated FA is added via AT to form phosphatidic acid. This is further converted to diacylglycerol (DAG) via phosphatase. Diacylglycerol acyltransferase (DGAT) then converts DAG to TAG [12]. The liver packages TAG with other substrates to form very low density lipoproteins (VLDL). These VLDLs enter the blood stream for transport of TAGs to other cells within the body. TAGs are transferred in the blood via chylomicrons from enterocytes. Endogenously produced TAGs are carried via VLDL and TAGs absorbed from the diet in enterocytes are carried in the blood via chylomicrons [10]. These TAGs are a main source of energy for normal metabolic cellular function [13].
JianPi-QingHua formula attenuates nonalcoholic fatty liver disease by regulating the AMPK/SIRT1/NF-κB pathway in high-fat-diet-fed C57BL/6 mice
Published in Pharmaceutical Biology, 2023
Jing Tian, Mengjie Cai, Shenyi Jin, Qingguang Chen, Jiahui Xu, Qiuyue Guo, Zihui Yan, Xu Han, Hao Lu
The AMPK/SIRT1 pathway affected lipid metabolism through the following genes including lipogenesis, lipolysis and triglyceride synthesis. As presented in Figure 5(G), the expression of lipogenesis-related genes including Sterol Regulatory Element-Binding Protein (SREBP1) and fatty acid synthase (FASN) were remarkably elevated in HFD-fed mice (p < 0.05), and JPQH reduced the expression of SREBP1 and FASN (p < 0.05). In addition, JPQH lowered the mRNA level of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in the liver, which are lipolysis-related genes (Figure 5(H)). In the wake of JPQH administration, diacylglycerol acyltransferase (DGAT), the triglyceride synthesis, was downregulated (Figure 5(I)). The above experiments indicated that JPQH inhibited hepatic lipid accumulation by activating the AMPK/SIRT1 pathway.
Related Knowledge Centers
- Chylomicron
- Diglyceride
- Enterocyte
- Isozyme
- Lactation
- Triglyceride
- Acyl-Coa
- Committed Step
- Mboat
- Dgat1