Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The low density lipoprotein receptor-related protein (LRP) is a cell surface receptor that binds and internalizes several macromolecules including apolipoprotein E-enriched remnant lipoproteins and protease/antiprotease complexes such as activated alpha 2-macroglobulin. Its function has been studied primarily in cultured fibroblasts and in liver. In the current studies, we provide evidence that LRP is present on the surface of primary adipocytes isolated from rat epididymal fat pads. The activity of the receptor increases 2-3-fold within minutes after the adipocytes are exposed to physiological concentrations of insulin as indicated by an increase in the uptake of 125I-labeled activated alpha 2-macroglobulin. There is a corresponding increase in the uptake of [3H]cholesteryl esters from radiolabeled apoE-enriched beta-very low density lipoprotein. The latter uptake was inhibited by an antibody against LRP and by a fusion protein containing the 39-kDa protein, also called receptor-associated protein, a known inhibitor of LRP function. In vivo, rats that had been fed ad libitum accumulated approximately 24-fold more chylomicron cholesteryl esters in their epididymal fat pads than did fasted control animals. We suggest that insulin stimulation of LRP, in a synergistic action with lipoprotein lipase, increases the endocytic uptake of cholesteryl esters and triglycerides from remnant lipoproteins in postprandial adipocytes.
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PMID:Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes. 767 62

CD24 is a glycophosphatidylinositol (GPI)-linked cell surface receptor that is involved in regulating the survival or differentiation of several different cell types. CD24 has been used to identify pre-adipocytes that are able to reconstitute white adipose tissue (WAT) in vivo. Moreover, we recently found that the dynamic upregulation of CD24 in vitro during early phases of adipogenesis is necessary for mature adipocyte development. To determine the role of CD24 in adipocyte development in vivo, we evaluated the development of the inguinal and interscapular subcutaneous WAT and the epididymal visceral WAT in mice with a homozygous deletion of CD24 (CD24KO). We observed a significant decrease in WAT mass of 40% to 74% in WAT mass from both visceral and subcutaneous depots in male mice, with no significant effect in female mice, compared to wild-type (WT) sex- and age-matched controls. We also found that CD24KO mice had increased fasting glucose and free fatty acids, decreased fasting insulin, and plasma leptin. No major differences were observed in the sensitivity to insulin or glucose, or in circulating triglycerides, total cholesterol, HDL-cholesterol, or LDL-cholesterol levels between WT and CD24KO mice. Challenging the CD24KO mice with either high sucrose (35%) or high fat (45%) diets that promote increased adiposity, increased WAT mass and fasting insulin, adiponectin and leptin levels, as well as reduced the sensitivity to insulin and glucose, to the levels of WT mice on the same diets. The CD24-mediated reduction in fat pad size was due to a reduction in adipocyte cell size in all depots with no significant reduction pre-adipocyte or adipocyte cell number. Thus, we have clearly demonstrated that the global absence of CD24 affects adipocyte cell size in vivo in a sex- and diet-dependent manner, as well as causing metabolic disturbances in glucose homeostasis and free fatty acid levels.
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PMID:Loss of CD24 in Mice Leads to Metabolic Dysfunctions and a Reduction in White Adipocyte Tissue. 2653 76

Adipose tissue dysfunction in obesity and lipodystrophy results in major health complications such as heart disease and stroke, and is associated with an increased risk of some cancers. We have previously found that the cell surface receptor CD24 regulates adipogenesis as measured by lipid accumulation and gene expression in mature adipocytes. How CD24 regulates these processes remains unknown. To begin answering this question, we first determined that CD24 does not affect glucose uptake in differentiating adipocytes in vitro. We then examined changes in global gene expression via DNA microarray in 3T3-L1 adipocytes with siRNA-mediated knock-down of CD24 expression. We found that CD24 expression is necessary for upregulation of up to 134 genes. We validated the CD24-mediated regulation of 4 of these genes during in vitro adipogenesis of 3T3-L1 and primary cells isolated from the inguinal white adipose tissue depots of CD24 knockout mice. Surprisingly, we found that only 1 of these genes was also regulated by CD24 in cells from the epididymal depot. Overall, these data suggest that CD24 is necessary for select gene expression in a depot-specific manner during adipogenesis in vitro. These findings could help elucidate the mechanisms regulating lipid accumulation in adipocytes thereby aiding in the development of novel treatment strategies for obesity and lipodystophy.
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PMID:CD24 is required for regulating gene expression, but not glucose uptake, during adipogenesis. 3023 71