Hepatic triglyceride

PPARy is a transcription factor which controls the expression of enzymes and proteins involved in fat and glucose metabolism. More importantly, stimulation of this receptor induces differentiation of preadipocytes to adipose cells. It is believed that the formation of additional, small fat cells lowers free fatty acids and hepatic triglycerides, thereby collecting insulin resistance. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Wolfe has presented an excellent description of the systematic application of stable and radioactive isotope tracers in determining the kinetics of intestinal fat absorption, hepatic triglyceride synthesis, lipid mobilization, triglyceride-fatty acid recycling, and cholesterol turnover. 

Selected entries from Methods in Enzymology [vol, page(s)] Detergent-resistant phospholipase Ai from Escherichia coll membranes, 197, 309 phospholipase Ai activity of guinea pig pancreatic lipase, 197, 316 purification of rat kidney lysosomal phospholipase Ai, 197, 325 purification and substrate specificity of rat hepatic lipase, 197, 331 human postheparin plasma lipoprotein lipase and hepatic triglyceride lipase, 197, 339 phospholipase activity of milk lipoprotein lipase, 197, 345. 

Pharmacology Nicotinic acid (but not nicotinamide) in gram doses produces an average 10% to 20% reduction in total and LDL cholesterol, a 30% to 70% reduction in triglycerides, and an average 20% to 35% increase in HDL cholesterol. Nicotinic acid also decreases serum levels of apolipoprotein B-100, the major component of VLDL and LDL fractions. The mechanism by which nicotinic acid exerts these effects is not entirely understood but may involve several actions, including a decrease in esterification of hepatic triglycerides. 

Labbe, G. et al. (1991) Effects of various tetracycline derivatives on in vitro and in vivo beta-oxidation of fatty acids, egress of triglycerides from the liver, accumulation of hepatic triglycerides, and mortality in mice. Biochemical Pharmacology, 41 (4), 638-641. 

Mechanism of Action Afibricacid derivative that inhibits lipolysis of fat in adipose tissue decreases liver uptake of free fatty acids and reduces hepatic triglyceride production. Inhibits synthesis of VLDL carrier apolipoprotein B. Therapeutic Effect Lowers serum cholesterol and triglycerides (decreases VLDL, LDL increases HDL). Pharmacokinetics Well absorbed from the GI tract. Protein binding 99%. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life 1.5 hr. 

Baginsky ML, Brown WV (1979) A newmethodfor the measurement of lipoprotein lipase in postheparin plasma using sodium dodecyl sulfate for the inactivation of hepatic triglyceride lipase. J Lipid Res 20 548-556... 

Yamagishi S, Abe T, Sawada T. Human recombinant interferon alpha-2a (r IFN alpha-2a) therapy suppresses hepatic triglyceride lipase, leading to severe hypertriglyceridemia in a diabetic patient. Am J Gastroenterol 1994 89(12) 2280. 

Wistar) (GO) Other 7.5 (decreased plasma triglyceride levels) foci of necrotic cells, increased hepatic triglyceride levels, vesiculation and dispersion of ribosomal granules in the endoplasmic reticulum, increased AST) 1969... 

Figure 3 Function of CETP, LPL (lipoprotein lipase) and HTGL (hepatic triglyceride...

LCAT), which catalyzes the synthesis of cholesterol esters (F14, S46, S59) apoA-II, which activates hepatic triglyceride lipase (J2) and apoC-II, which activates lipoprotein lipase, responsible for the hydrolysis of triglycerides in chylomicrons and VLDL (H20, L5). Their mode of action is considered in Section 4 when the individual apolipoproteins are discussed. 

Purified apoA-II was shown by Jahn et al. (J2) to increase hepatic triglyceride lipase activity by threefold in vitro. Human plasma also activates hepatic triglyceride lipase activity, and it is a reasonable assumption that this activation is due to apoA-II. The physiological importance of this effect is not yet clear. 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

In functional lipoprotein lipase deficiency there appears to be a normal removal rate for VLDL from the plasma (B31, F19, N7), and an unimpaired rate for the conversion of VLDL apoB to LDL apoB (N7). It may be that VLDL is hydrolyzed by hepatic triglyceride lipase (unaffected in lipoprotein lipase deficiency) (N7). Hepatic triglyceride lipase does not require apoC-II as a cofactor (E2). 

As hepatic triglyceride lipase is released into the circulation by heparin, it might be thought that postheparin plasma hepatic triglyceride lipase activity... 

M46. Murase, T., and Hakura, H., Accumulation of intermediate density lipoprotein in plasma after intravenous administration of hepatic triglyceride lipase antibody in rats. Atherosclerosis 38, 293-300 (1981). 

R6. Reardon, M. F.,. Sakai, H., and Steiner, G., Roles of lipoprotein lipase and hepatic triglyceride lipase in the catabolism in vivo of triglyceride-rich lipoproteins. Arteriosclerosis 2, 396-402 (1982). 

Nicotinic acid inhibits hepatic triglyceride production and VLDL secretion, which lowers the plasma level of LDL and increases HDL. Nicotinic acid is mostly used to treat elevated LDL and VLDL by decreasing VLDL synthesis. 

Effect of DHA on hepatic triglyceride metabolism in diet-induced... 

EFFECT OF DHA ON HEPATIC TRIGLYCERIDE METABOLISM IN DIET-INDUCED LIPODYSTROPHY MODEL MICE... 

Figure 223. Effect of DHA on hepatic triglyceride levels and serum alanine aminotransferase (ALT) levels in diet-induced lipodystrophy model mice.

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