Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The socio-economic impact of obesity, one of the most prevalent medical disorders in Western society, is mainly due to its association with a higher risk of coronary heart disease. It is likely that atherosclerosis develops against a background of obesity as a result of the insulin resistance that is invariably present in overweight and obese subjects. Fasting plasma lipids may be normal in obese subjects, but they are usually affected by postprandial hyperlipidemia, which is probably due to competition between chylomicrons and VLDL for the same metabolic pathways. The basis for the impaired clearance of atherogenic chylomicron remnants is the fact that obesity causes hepatic apo B-VLDL overproduction, and thus leads to competition with chylomicrons and their remnants at the lipolytic pathway (lipoprotein lipase and hepatic lipase) and receptor level (LDL-receptor and remnant-receptor). The overproduction of VLDL is probably caused by an enhanced hepatic flux of free fatty acids in both the postprandial (from the lipolysis of triglyceride rich particles) and postabsorptive states (from adipocytes). Weight reduction by means of life-style changes, supported by medical interventions with inhibitors of intestinal fat absorption (e.g. Orlistat) or appetite suppressants (e.g. Sibutramine), is essential in order to decrease the risk of atherosclerosis. Furthermore, improvement of risk factors can be achieved by means of fibrate treatment to modulate fasting and postprandial triglyceride levels. Treatment with cholesterol synthesis inhibitors ("statins") may reduce hepatic VLDL production and increase the clearance of atherogenic remnants by upregulating LDL-receptors, thus leading to improved fasting lipid levels and enhanced clearance of chylomicron remnants. Finally, the use of thiazolidinedione derivatives to improve insulin sensitivity may be one of the options for reducing the risk of atherosclerosis in obese subjects.
 ...
PMID:Obesity and free fatty acids: double trouble. 1143 90

In the normal population, the prevalence of obesity is almost 20%. It is a condition influenced by genetic factors, so that individual behavior cannot be regarded as its sole cause. The amount of food is essentially determined by the hormone leptin, the feedback regulation of which can be disturbed by a modification of the molecule or a mutation of the receptor. A further important determinant is energy consumption, which is subject to large individual variations, which partly result from thermogenesis. With regard to the fat distribution, it is concentrated on the trunk in the android form as compared to the hips in the gynecoid form. The android form is subject to a higher incidence of cardiovascular morbidity and mortality. The indirect determination of body fat by measuring the body mass index (weight [kg]/body weight [m(2)]) is hence less reliable than measuring the waist (women > 80 cm, men > 94 cm). The effects of generalized obesity on cardiovascular function are chiefly an increase of blood volume and an eccentric left ventricular hypertrophy. This first of all results in diastolic dysfunction, which can give rise to a disturbance of systolic function in left ventricular dilatation. Concentric hypertrophy develops in the presence of arterial hypertension. This is twice as frequent in obese patients than in the normal population, which is due to increased activity of the sympathetic nervous system and stimulation of the renin-angiotensin system. A disturbance of lipid metabolism is observed four to six times more frequently. The qualitative change in LDL fraction with a raised concentration of low density LDL particles appears to be of crucial importance. With increasing fat mass, the sensitivity to insulin is lowered, so that in obesity the risk of developing diabetes mellitus type 2 is tripled. Since there has been a dramatic increase in the numbers of overweight children and adolescents (from 10.5% to 15.5% within the past five years), prevention programs should be started in good time. A reduction in calorie intake and an altered dietary composition (55% complex carbohydrates, 30% fat and 15% to 20% protein) on the one hand, and increased physical activity on the other hand continue to be the central components. The latter is especially effective when it regularly gives rise to an increased turnover of fatty acids as a result of an increased energy metabolism at moderate intensity. This leads to adaptation, i. e. an increase in the activity of lipoprotein lipase. If prevention programs and/or changes in lifestyle do not give rise to the desired weight reduction, medication is indicated in some adults. Sibutramine (Reductil and orlistate (Xenical) lead to an additional weight loss of up to 10%. However, consistent treatment of any cardiovascular risk factors present is more important. Treatment of arterial hypertension is of greatest prognostic significance, especially in concomitant diabetes mellitus. In individual cases and after thorough discussion of indication surgical options should be considered.
 ...
PMID:[Obesity and cardiovascular diseases-theoretical background and therapeutic consequences]. 1524 61