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Updated: May 11, 2026

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
Published on: March 28, 2013
Orexin receptor-1 mediates brown fat developmental differentiation
Dyan Sellayah1, Devanjan Sikder
1Metabolic Signaling and Disease Program; Diabetes and Obesity Research Center; Sanford-Burnham Medical Research Institute; Orlando, FL USA.
Abstract:
Orexin A (OX) is a small excitatory neuropeptide hormone that stimulates feeding, wakefulness and energy expenditure via a pair of G-coupled protein receptors, namely orexin receptor-1 (OXR1) and orexin receptor-2 (OXR2). OX-deficient mice are sensitive to obesity despite being hypophagic. The obesogenic effect of OX-deletion is due to brown adipose tissue (BAT) dysfunction, a defect that originates during fetal growth. Brown preadipocytes in OX-null mice display undifferentiated histological appearance and fail to support both diet- and cold-induced thermogenesis. We show that the OXR1-null mice phenocopies the differentiation defect observed in the ligand-null mice indicating that OXR1 relays OX's differentiation and thermogenic function. Consistent with this, OX fails to induce differentiation in cultured OXR1-null preadipocytes. Thus, OX signaling via OXR1 constitutes an important thermoregulatory mechanism that defends against cold and obesity.
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