scholarly journals Preferential lipolysis of DGAT1 over DGAT2 generated triacylglycerol in Huh7 hepatocytes

2021 ◽  
Author(s):  
Rajakumar Selvaraj ◽  
Sarah V Zehnder ◽  
Russell Watts ◽  
Jihong Lian ◽  
Randal Nelson ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Neutral Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Hepatoma Cells ◽  
Fatty Acid Production ◽  
Steryl Esters ◽  
Small Change ◽  
Lipoprotein Assembly

Hepatic steatosis is defined by accumulation of neutral lipids in lipid droplets (LDs) including triacylglycerol (TG) and steryl esters. Two distinct diacylglycerol acyltransferases (DGAT1 and DGAT2) catalyze synthesis of TG in hepatocytes. TG formed through either DGAT1 or DGAT2 appears to be preferentially directed to distinct intercellular fates, such as fatty acid production for oxidation or very-low density lipoprotein assembly, respectively. Because of the preferential use of TG generated by DGAT1 and DGAT2, we hypothesized that targeting/association of lipolytic machinery to LDs would differ depending on whether the TG stores were generated through DGAT1 or DGAT2 activities. Inhibition of DGAT1 or DGAT2 in human hepatoma cells (Huh7) incubated with oleic acid resulted in only a small change in TG accretion suggesting that the two DGATs can compensate for each other in fatty acid esterification. This compensation was not accompanied by changes in DGAT1 or DGAT2 mRNA expression. DGAT1 inhibition (TG synthesized by DGAT2) resulted in large LDs, whereas DGAT2 inhibition (TG synthesized by DGAT1) caused the accumulation of numerous small LDs. Oleic acid treatment increased mRNA and protein expression of the LD-associated protein PLIN2 but not PLIN5 or the lipase ATGL and its activator ABHD5/CGI-58. Inactivation of DGAT1 or DGAT2 did not alter expression (mRNA or protein) of ATGL, ABHD5/CGI-58, PLIN2 or PLIN5, but inactivation of both DGATs increased PLIN2 abundance despite a dramatic reduction in the number of LDs. ATGL localized preferentially to DGAT1- made LDs rather than to DGAT2-made LDs, and TG in these LDs was preferentially used for fatty acid (FA) oxidation. A combination of DGAT2 inhibitor and the pan lipase inhibitor E600 resulted in large LDs, suggesting that the small size of DGAT1-made LDs is due to a lipolytic process.

Intestinal triglycerides are derived from both endogenous and exogenous sources

1985 ◽  
Vol 248 (2) ◽  
pp. G164-G169 ◽  
Author(s):  
Y. F. Shiau ◽  
D. A. Popper ◽  
M. Reed ◽  
C. Umstetter ◽  
D. Capuzzi ◽  
...  
Keyword(s):  
Small Intestine ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Dietary Lipid ◽  
Acid Load ◽  
Endogenous Substrates ◽  
Quantitative Contribution ◽  
Vldl Triglyceride

Although studies have indicated that the small intestine is capable of utilizing endogenous substrates for triglyceride synthesis in the absence of dietary lipid, the importance of the endogenous contribution to total intestinal triglyceride production during absorption has not yet been defined. In this study we have examined the quantitative contribution of endogenous triglyceride production during different luminal lipid loads. By use of a mesenteric lymph fistula rat model with total parenteral nutritional support, mesenteric lymphatic triglyceride transport was investigated. Our results indicate that, during absorption, a substantial fraction (greater than 50%) of total triglyceride is derived from endogenous sources. Increased luminal fatty acid loads lead to an increase in both endogenous and exogenous triglyceride production. Incorporation of luminally infused oleic acid into triglyceride carried by chylomicrons is dependent on the luminal fatty acid load, while incorporation of oleic acid into very low-density lipoprotein (VLDL) triglyceride is saturable. We conclude that both chylomicron and VLDL are involved in transporting triglyceride derived from both endogenous and exogenous sources. The different patterns in the partition of endogenous and exogenous triglyceride into chylomicrons and VLDL suggest that these two lipid-carrying lipoproteins are probably packaged differently in the small intestine.

scholarly journals The role of selenium in the secretion of very-low-density lipoprotein in the isolated perfused rat liver

1991 ◽  
Vol 279 (3) ◽  
pp. 741-745 ◽  
Author(s):  
R L Scott ◽  
A Kheshti ◽  
M Heimberg ◽  
H G Wilcox ◽  
W L Stone
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Low Density Lipoprotein ◽  
Liver Perfusion ◽  
Density Lipoprotein ◽  
Acid Oxidation ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Deficient Diet

A recirculating liver perfusion system was used to study the effects of dietary selenium (Se) on the hepatic secretion of very-low-density lipoprotein (VLDL). The perfusate from livers of rats fed on a Se-deficient diet incorporated about 50% more [1-14C]oleic acid into triacylglycerol (TG) and cholesteryl esters (ChoEs) than did the perfusate from livers of rats fed on a Se-supplemented diet. Similarly, livers from rats fed the Se-deficient diet secreted more VLDL and incorporated about 60% more [1-14C]oleic acid into VLDL TG and ChoEs than did livers from rats fed the Se-supplemented diet. The liver perfusate from rats in the Se-deficient group also showed significantly decreased fatty acid oxidation. We conclude that Se is a potent modulator of lipoprotein metabolism. A primary action of Se deficiency appears to be a decrease in fatty acid oxidation and a stimulation of fatty acid esterification, leading to increased VLDL TG and ChoEs formation and secretion.

scholarly journals TILLING-by-Sequencing+ Reveals the Role of Novel Fatty Acid Desaturases (GmFAD2-2s) in Increasing Soybean Seed Oleic Acid Content

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1245
Author(s):  
Naoufal Lakhssassi ◽  
Valéria Stefania Lopes-Caitar ◽  
Dounya Knizia ◽  
Mallory A. Cullen ◽  
Oussama Badad ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Acid Content ◽  
Edible Oils ◽  
Fatty Acid Desaturase ◽  
Soybean Seed ◽  
Oleic Acid Content ◽  
Fatty Acid Production ◽  
Tilling By Sequencing

Soybean is the second largest source of oil worldwide. Developing soybean varieties with high levels of oleic acid is a primary goal of the soybean breeders and industry. Edible oils containing high level of oleic acid and low level of linoleic acid are considered with higher oxidative stability and can be used as a natural antioxidant in food stability. All developed high oleic acid soybeans carry two alleles; GmFAD2-1A and GmFAD2-1B. However, when planted in cold soil, a possible reduction in seed germination was reported when high seed oleic acid derived from GmFAD2-1 alleles were used. Besides the soybean fatty acid desaturase (GmFAD2-1) subfamily, the GmFAD2-2 subfamily is composed of five members, including GmFAD2-2A, GmFAD2-2B, GmFAD2-2C, GmFAD2-2D, and GmFAD2-2E. Segmental duplication of GmFAD2-1A/GmFAD2-1B, GmFAD2-2A/GmFAD2-2C, GmFAD2-2A/GmFAD2-2D, and GmFAD2-2D/GmFAD2-2C have occurred about 10.65, 27.04, 100.81, and 106.55 Mya, respectively. Using TILLING-by-Sequencing+ technology, we successfully identified 12, 8, 10, 9, and 19 EMS mutants at the GmFAD2-2A, GmFAD2-2B, GmFAD2-2C, GmFAD2-2D, and GmFAD2-2E genes, respectively. Functional analyses of newly identified mutants revealed unprecedented role of the five GmFAD2-2A, GmFAD2-2B, GmFAD2-2C, GmFAD2-2D, and GmFAD2-2E members in controlling the seed oleic acid content. Most importantly, unlike GmFAD2-1 members, subcellular localization revealed that members of the GmFAD2-2 subfamily showed a cytoplasmic localization, which may suggest the presence of an alternative fatty acid desaturase pathway in soybean for converting oleic acid content without substantially altering the traditional plastidial/ER fatty acid production.

scholarly journals Effect of atorvastatin and rosuvasta tin on the fatty acid spectrum of lymphocyte membranes in patients with unstable angina

2020 ◽  
pp. 92-95
Author(s):  
T.V. Bogdan ◽  
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Unstable Angina ◽  
Unsaturated Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Membrane Phospholipids ◽  
Stabilization Of Membranes ◽  
Dynamic Structures

Numerous studies have demonstrated the superiority of rosuvastatin over other statins in the treatment of cardiovascular disease. It has been proven that rosuvastatin is more effectively lowers low-density lipoprotein cholesterol in patients with cardiovascular disease than other members of this drug group. Despite the known mechanisms of action of statins on blood lipids, their effective use in patients with cardiovascular disease, as well as side effects, the influence of these drugs on the fatty acid spectrum of lymphocyte (LC) membrane phospholipids in patients with ischemic heart disease remains unexplored. The results of the studies cited in the article indicate that, in patients with unstable angina who received the therapy that included rosuvastatin, unlike patients receiving the basic treatment with atorvastatin, the relative phosphate lipid contents of palmitic, stearic, and stearin arachidonic polyunsaturated fatty acids and the amount of unsaturated fatty acids are normalized, which testifies to the stabilization of membranes as dynamic structures.

scholarly journals AUP1 (Ancient Ubiquitous Protein 1) Is a Key Determinant of Hepatic Very-Low–Density Lipoprotein Assembly and Secretion

2017 ◽  
Vol 37 (4) ◽  
pp. 633-642 ◽  
Author(s):  
Jing Zhang ◽  
Mostafa Zamani ◽  
Christoph Thiele ◽  
Jennifer Taher ◽  
Mohsen Amir Alipour ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Assembly

scholarly journals ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue

2020 ◽  
Vol 11 ◽  
Author(s):  
Katsumi Iizuka ◽  
Ken Takao ◽  
Daisuke Yabe
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Whole Body ◽  
Acetyl Coa ◽  
Alcoholic Fatty Liver

Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines.

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