In Vivo Identification of Bipotential Adipocyte Progenitors Recruited by β3-Adrenoceptor Activation and High-Fat Feeding

Abstract

Summary Nutritional and pharmacological stimuli can dramatically alter the cellular phenotypes in white adipose tissue (WAT). Utilizing genetic lineage tracing techniques, we demonstrate that brown adipocytes (BA) that are induced by β3-adrenergic receptor activation in abdominal WAT arise from the proliferation and differentiation of cells expressing platelet-derived growth factor receptor alpha (PDGFRα), CD34 and Sca1 (PDGFRα+ cells). PDGFRα+ cells have a unique morphology in which extended processes contact multiple cells in the tissue microenvironment. Surprisingly, these cells also give rise to white adipocytes (WA) that can comprise up to 25% of total fat cells in abdominal fat pads following 8 weeks of high fat feeding. Isolated PDGFRα+ cells differentiated into both BA and white adipocytes (WA) in vitro, and generated WA after transplantation in vivo. The identification of PDGFRα+ cells as bipotential adipocyte progenitors will enable further investigation of mechanisms that promote therapeutic cellular remodeling in adult WAT.

Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats

“…Cold exposure-driven macrophage infi ltration may also be somehow connected to an increased sympathetic activity leading to catabolism in the adipose tissue. Treatment with a β3-adrenergic agonist triggers the death of numerous unilocular white adipocytes, followed by clearance of the dead fat cells (eff erocytosis) by resident macrophages that assume an M2 phenotype and a subsequent brown/ beige adipogenesis in gonadal white adipose tissue (Lee et al 2012;. Liu et al (2015) have shown that receptor Interacting Protein 140 (RIP140) may play a key role in regulating the balance of M1/M2 macrophages in the white adipose tissue.…”

Brown and beige fat: development, function and therapeutic potential

“…After treatment of mice with β3-adrenergic agonists, these precursor cells proliferate, lose Pdgfr-α expression and differentiate into Ucp1 + adipocytes. Conversely, a high-fat diet stimulates the differentiation of Pdgfr-α + cells into white adipocytes 34 . This result is consistent with the finding that most or all white adipocytes descend from Pdgfra-expressing cells 35 .…”

“…However, Ucp1-expressing adipocytes are evident in most (if not all) WAT depots in response to cold exposure 7,30,33 . In perigonadal (visceral) fat of male mice, beige adipocytes develop from a population of precursors that also differentiates into white adipocytes 34 (Fig. 2b).…”

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

“…[11][12][13]15 Although cellular origins of beige adipocytes remain poorly understood, these cells in the epididymal WAT of rodents are derived through proliferation and differentiation of precursors that express PDGFRα (plateletderived growth factor receptor α) and SCA1 (spinocerebellar ataxia type 1). 16 A recent paper reported that~10% of the UCP1-positive beige adipocytes in inguinal WAT arise from smooth muscle precursors that express Myh11. 17 In addition, a subset of beige adipocytes in anterior subcutaneous and perigonadal WAT depots originates from Myf5-positive cells, 18 whereas most of beige adipocytes in inguinal WAT derive from Myf5-negative precursors.…”