Tissue-specific regulation of lipoprotein lipase.
Year: 1992
Type: article
Abstract: L ipoprotein lipase (LPL) hydrolyses the triglyceride component of circulating lipoprotein particles, chylomicrons and very-low-density lipoproteins to provide fatty acids for tissue use. The enzyme is found in adipose tissue, cardiac and skeletal muscle, lactating mammary gland, lung, spleen and brain,' where it catalyses the rate-controlling step for lipid acquisition from circulating triglycerides. It thus plays a key role in normal fuel metabolism; accordingly, familial LPL deficiency produces profound hypertriglyceridemia. In addition, the regulation of LPL is important in disorders of lipid metabolism associated with obesity and diabetes mellitus. Although LPL is encoded by a single gene, its activity is regulated in a tissue-specific manner. For example, with fasting, LPL activity decreases in adipose tissue but increases in cardiac tissue; as a result, triglyceride fatty acids are diverted away from storage to meet the metabolic demands of the heart.' In contrast, a 6-hour insulin and glucose infusion given to normal-weight fasting subjects caused LPL activity to increase threefold in adipose tissue but to decrease significantly in skeletal muscle.2 Therefore, insulin directs triglyceride fatty acids away from muscle oxidation and toward storage. Patients with poorly controlled diabetes have decreased adipose tissue LPL activity, which accounts in part for their hypertriglyceridemia; therapy with insulin or glyburide increases LPL activity and immunoreactive mass in adipose tissue.3 LPL activity is greater in gluteal adipose tissue than in abdominal adipose tissue in premenopausal women of normal weight;45 the opposite pattern is observed in men.4 Thus, regional differences in adipose tissue LPL activity may underlie variations in body fat deposition. In obese women LPL activity is markedly increased in both gluteal and abdominal adipose tissue to values that are no longer different.5 The extent of the increase in LPL activity in the two regions after an insulin and glucose infusion is the same for normal-weight and obese women.5 Tissue-specific regulation of LPL is physiologically important because it directs the use of triglyceride fatty acids according to metabolic demands. The underlying cellular mechanisms remain enigmatic. Control of LPL gene expression by specific DNA binding elements is likely important along with regulation at other sites in the biosynthetic pathway for LPL.' In human adipose tissue the stimulation of LPL activity by insulin therapy is associated with increased synthesis of LPL protein but no change in LPL messenger RNA levels, which suggests hormonal regulation of translation.3
Source: Europe PMC (PubMed Central)
Authors: J E Braun, D L Severson
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1819430874