Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orphan nuclear receptors of the peroxisome proliferator activated receptor (PPAR) and liver X receptor (LXR) subfamilies have been shown to play critical roles in both local and systemic lipid metabolism. The PPARs control fatty acid metabolism in various cell types, including adipocytes, liver, and macrophages. The LXRs have been implicated in the regulation of cholesterol metabolism in the liver, intestines, and macrophages. The importance of these receptors in physiologic lipid metabolism suggests that they may influence the development of metabolic disorders such as obesity, diabetes, and atherosclerosis. Furthermore, the ability of these receptors to be modulated pharmacologically makes them attractive therapeutic targets. This review focuses on the role of PPAR and LXR signaling pathways in macrophage lipid metabolism and the potential of these pathways to modulate the development of atherosclerosis.
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PMID:Orphan nuclear receptors find a home in the arterial wall. 1193 19

Orphan nuclear receptors provide a unique resource for uncovering novel regulatory systems that impact human health and also provide drug targets for a variety of human diseases. Ligands of nuclear receptors have been used in several important therapeutic areas, such as breast cancers, skin disorders and diabetes. Orphan nuclear receptors, therefore, represent a tremendous opportunity in understanding and treating human diseases. Here, I highlight recent advances in the use of orphan nuclear receptors and their potential as targets for drug discovery in diabetes, obesity, neurodegenerative diseases and other related disorders.
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PMID:Orphan nuclear receptors in drug discovery. 1753 27

Orphan receptor small heterodimer partner (SHP, NROB2) has been shown to be a metabolic regulator in pathways associated with several major aspects of the metabolic syndrome. However, the significance and transcriptional regulatory role of SHP in adipocyte differentiation remain unclear. Transcriptional profiles of 3T3-L1 preadipocytes and early differentiating preadipocytes in response to SHP were systemically surveyed using Affymetrix Genome Array representing well-characterized 14,000 genes. Analysis revealed about 963 genes that were up- or down-regulated by more than 2-fold during differentiation and/or by the overexpression of SHP. These genes were organized into 4 clusters that demonstrated concerted changes in expression of genes controlling various aspects of the cellular events and metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of several key regulators and stimulators of the adipogenic program as potential new SHP targets. Overexpression of SHP inhibited the differentiation process as well as the accumulation of neutral lipids within the cells. Our data suggests that SHP may function as a molecular switch that governs adipogenesis and a potent adipogenic suppressor that maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors and stimulators. Developing SHP agonist may promise a future treatment for obesity.
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PMID:Gene expression profiling reveals a diverse array of pathways inhibited by nuclear receptor SHP during adipogenesis. 1907 22