Hepatic triglyceride metabolism, effects

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

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

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. 

Nicotinic acid exerts a variety of effects on lipoprotein metabolism (7,16,49). One of its most important actions is the inhibition of lipolysis in adipose tissue. This initial inhibition, like those of previously discussed antihyperlipidemic agents, produces a sequence of events that ultimately result in the lowering of plasma triglycerides and cholesterol. Impaired lipolysis decreases the mobilization of free fatty acids, thus reducing their plasma levels and their delivery to the liver. In turn, this decreases hepatic triglyceride synthesis and results in a decreased production of VLDL. Enhanced clearance of VLDL through stimulation of lipoprotein lipase also has been proposed to contribute to the reduction of plasma VLDL levels. Because LDL is derived from VLDL (Fig. 30.5), the decreased production of VLDL ultimately leads to a decrease in LDL levels. The sequential nature of this process has been clinically demonstrated. The reduction in triglyceride levels occurs within several hours after ... 

That portion of acetyl CoA which has been already been converted into citrate may be exported into the cytoplasm where it will act as a substrate for fatty add synthesis. As mentioned above, this may be followed by increased hepatic triglyceride synthesis and lead to hypertriglycerid-aemia. Alternatively, some of the excess acetyl CoA may be incorporated into 3-hydroxy-3-methylglutaryl CoA which is a starting point for cholesterol synthesis or the formation of ketone bodies that may increase addosis. This addosis can inhibit urea excretion by the kidney which in turn may exacerbate symptoms of gout. A summary diagram of the main effects of ethanol on metabolism is shown in Figure 29.3. 

Mechanism of Action An antihyperlipidemicthat interferes with cholesterol biosynthesis by inhibiting the conversion of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate, a precursor to cholesterol. Therapeutic Effect Decreases LDL cholesterol, VLDL, and plasma triglyceride levels, increases HDL concentration. Pharmacokinetics Protein binding 88%. Minimal hepatic metabolism. Primarily eliminated in the feces. Half-life 19 hr (increased in patients with severe renal dysfunction). 

A metabolic product of fiber fermentation, propionate may mediate some of the hypocholesterolemic effects of certain soluble plant fibers. In cholesterol-fed rats, propionate decreases serum cholesterol and liver triglyceride level where no changes in hepatic histology in response to propionate intake have been detected (Wang and Ng, 1999). 

Medium-chain triglycerides solubilize 192 mg of clomethizole edisilate in Heminevrin Capsules soft gelatin capsules (60 mg equivalent of clomethiazole). Clomethiazole is an oily viscous liquid as the free base but the edisilate (ethanedisulfonate) salt is a solid. Clomethiazole is a short-acting hypnotic and sedative with anticonvulsant effects, and Heminevrin is indicated for treatment of resdessness and insomnia that accompany alcohol withdrawal. Clomethiazole has a short half-life and low bioavailability due to extensive hepatic hrst-pass metabolism. The dose of Heminevrin is one to four capsules as needed, and the capsules are stored at room temperature. Heminevrin Capsules have been available in the United Kingdom since 1998. 

---