Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of a retinoid X receptor (RXR) to heterodimerize with many nuclear receptors, including LXR, PPAR, NGF1B and RAR, underscores its pivotal role within the nuclear receptor superfamily. Among these heterodimers, PPAR:RXR is considered an important signalling mediator of both PPAR ligands, such as fatty acids, and 9-cis retinoic acid (9-cis RA), an RXR ligand. In contrast, the existence of an RXR/9-cis RA signalling pathway independent of PPAR or any other dimerization partner remains disputed. Using in vivo chromatin immunoprecipitation, we now show that RXR homodimers can selectively bind to functional PPREs and induce transactivation. At the molecular level, this pathway requires stabilization of the homodimer-DNA complexes through ligand-dependent interaction with the coactivator SRC1 or TIF2. This pathway operates both in the absence and in the presence of PPAR, as assessed in cells carrying inactivating mutations in PPAR genes and in wild-type cells. In addition, this signalling pathway via PPREs is fully functional and can rescue the severe hypothermia phenotype observed in fasted PPARalpha-/- mice. These observations have important pharmacological implications for the development of new rexinoid-based treatments.
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PMID:In vivo activation of PPAR target genes by RXR homodimers. 1510 26

All mammals harbor two types of adipose tissues that serve distinct physiological functions: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT functions mainly in the storage of excess energy, while BAT specializes in dissipating energy in the form of heat and functions as a defense against hypothermia and obesity. Since adult humans possess significant amounts of active BAT depots and it's mass inversely correlates with adiposity, BAT plays an important role in human obesity and energy homeostasis.New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Classical brown adipocytes are located mainly in dedicated BAT depots of rodents and infants. Beige adipocytes, on the other hand, reside mainly in subcutaneous WAT where they arise postnatally in response to certain external cues, such as chronic cold exposure and long-term treatment with PPAR- agonists, a process often referred to as the "browning" of WAT. Importantly, adult human BAT appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as insulin resistance and type2 diabetes. I will review recent progress in the molecular control of brown and beige adipocyte development and discuss emerging questions.(Presented at the 1912th Meeting, December 21, 2015).
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PMID:Engineering Fat Cell Fate to Fight Obesity and Metabolic Diseases. 2672 80