Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenetic mechanisms behind familial combined hyperlipidemia (FCHL) are unknown. However, exaggerated postprandial lipemia and excessive serum free fatty acid (FFA) concentrations have drawn attention to altered lipid storage and lipolysis in peripheral adipose tissue. Hormone-sensitive lipase (HSL) is the enzyme responsible for intracellular lipolysis in adipocytes and a decrease of adipocyte HSL activity has been demonstrated in Swedish FCHL subjects. The aim of the study was to investigate if adipose tissue HSL activity had any effect on lipid phenotype and if low HSL activity and FCHL were linked in Finnish FCHL families. A total of 48 family members from 13 well-characterized Finnish FCHL families and 12 unrelated spouses participated in the study. FCHL patients with different lipid phenotypes (IIA, IIB, IV) did not differ in adipose tissue HSL activity from each other or from the 12 normolipidemic spouses (P = 0.752). In parametric linkage analysis using an affecteds-only strategy the low adipose tissue HSL activity was not significantly linked with FCHL phenotype. However, we found a significant sibling-sibling correlation for the HSL trait (0.51, P < 0.01). Thus, a modifying or interacting role of HSL in the pathogenesis of FCHL could not be excluded.
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PMID:Reduced hormone-sensitive lipase activity is not a major metabolic defect in Finnish FCHL families. 1116 26

In patients with familial combined hyperlipidemia (FCHL) and type 2 diabetes (DM2) organ-specific differences in insulin resistance may exist. In FCHL and DM2 in vivo insulin mediated muscle glucose uptake and inhibition of lipolysis were studied by euglycemic hyperinsulinemic clamp. Insulin mediated glucose uptake was impaired to the same extent in both FCHL and DM2. Only FCHL subjects showed no reduction in plasma glycerol concentrations during insulin infusion and incomplete suppression of plasma free fatty acid (FFA) concentrations combined. This finding indicated that insulin-induced suppression of lipolysis, or glycerol/FFA utilization, or both, were impaired in FCHL, in contrast to DM2 or control subjects. To analyze these possibilities in more detail, control, FCHL, and DM2 adipocytes were studied in vitro. In contrast to adipocytes from DM2 or control subjects, no reduction in medium FFA concentration was detected with FCHL adipocytes after incubation with insulin. This finding indicated impaired intracellular FFA utilization, most likely impaired FFA re-esterification. Genetic linkage analysis in 18 Dutch families with FCHL revealed no evidence for involvement of LIPE, the hormone sensitive lipase gene, indicating that genetic variation in adipocyte lipolysis by LIPE is not the key defect in FCHL. In conclusion, FCHL as well as DM2 subjects exhibited in vivo insulin resistance to glucose disposal, which occurs mainly in muscle. FCHL subjects showed insulin resistant adipose tissue lipid metabolism, in contrast to DM2 and controls. The different pattern of organ-specific insulin resistance in FCHL versus DM2 advances our understanding of differences and similarities in phenotypes between these disorders.
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PMID:Evidence of insulin resistant lipid metabolism in adipose tissue in familial combined hyperlipidemia, but not type 2 diabetes mellitus. 1220 6

Hormone-sensitive lipase (HSL) is an intracellular neutral lipase that is capable of hydrolyzing triacylglycerols, diacylglycerols, monoacylglycerols, and cholesteryl esters, as well as other lipid and water soluble substrates. HSL activity is regulated post-translationally by phosphorylation and also by pretranslational mechanisms. The enzyme is highly expressed in adipose tissue and steroidogenic tissues, with lower amounts expressed in cardiac and skeletal muscle, macrophages, and islets. Studies of the structure of HSL have identified several amino acids and regions of the molecule that are critical for enzymatic activity and regulation of HSL. This has led to important insights into its function, including the interaction of HSL with other intracellular proteins, such as adipocyte lipid binding protein. Accumulating evidence has defined important functions for HSL in normal physiology, affecting adipocyte lipolysis, steroidogenesis, spermatogenesis, and perhaps insulin secretion and insulin action; however, direct links between abnormal expression or genetic variations of HSL and human disorders, such as obesity, insulin resistance, type 2 diabetes, and hyperlipidemia, await further clarification. The published reports examining the regulation, and function of HSL in normal physiology and disease are reviewed in this paper.
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PMID:Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. 1236 42