A Smooth Muscle-Like Origin for Beige Adipocytes

Long, Jonathan Z.; Svensson, Katrin J.; Tsai, Linus; Zeng, Xing; Roh, Hyun Cheol; Kong, Xingxing; Rao, Rajesh R.; Lou, Jesse; Lokurkar, Isha A.; Baur, Wendy; Castellot, John J.; Rosen, Evan D.; Spiegelman, Bruce M.

doi:10.1016/j.cmet.2014.03.025

Cited by 403 publications

(393 citation statements)

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“…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. These data suggest high cellular heterogeneity of beige adipocyte populations in multiple WAT depots.…”

Section: Developmental Lineages Of Brown and Beige Adipocytes In Micementioning

confidence: 99%

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

Kajimura

2015

Int J Obes Supp

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Obesity develops from a chronic energy imbalance in which energy intake exceeds energy expenditure. As brown adipose tissue (BAT) dissipates energy and produces heat, increasing energy expenditure via BAT thermogenesis may constitute a novel therapeutic intervention for the treatment of obesity and obesity-related diseases. Studies over the past few years have identified key regulatory molecules of brown and beige adipocyte biogenesis, including a dominant transcriptional co-regulator PRDM16 (PR domain containing 16) and its co-factors, which allows for engineering functional BAT by genetic approaches. A next step toward the goal of promoting BAT thermogenesis by pharmacological approaches necessitates a better understanding of the enzymatic components and signaling pathways for brown and beige adipocyte development. This review covers recent advances regarding this topic, with a special emphasis on the PRDM16 transcriptional pathway.

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Section: Developmental Lineages Of Brown and Beige Adipocytes In Micementioning

confidence: 99%

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

Kajimura

2015

Int J Obes Supp

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“…These adipocytes are commonly referred to as beige, brite (from brown in white), inducible, or recruitable, reviewed in Chechi et al 7 and seem to result from the transdifferentiation of previously unilocular, white adipocytes4, 5 and from the de novo differentiation of precursor cells 8. It has been proposed that beige adipocytes can derive from a distinct precursor and display a gene expression pattern different from that of brown adipocytes 9. Recent studies also reported the presence of BAT and the formation of UCP1‐expressing adipocytes within WAT depots in adult humans 10, 11.…”

Section: Introductionmentioning

confidence: 99%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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BackgroundIntramuscular fatty infiltration is generally associated with the accumulation of white adipocytes in skeletal muscle and unfavourable metabolic outcomes. It is, however, still unclear whether intramuscular adipocytes could also acquire a brown‐like phenotype. Here, we detected intramuscular expression of brown adipocyte markers during fatty infiltration in an obesity‐resistant mouse strain and extensively compared the potential of two different stem cell populations residing in skeletal muscle to differentiate into brown‐like adipocytes.MethodsFatty infiltration was induced using intramuscular glycerol or cardiotoxin injection in the tibialis anterior muscles of young or aged 129S6/SvEvTac (Sv/129) mice or interleukin‐6 (IL‐6) knockout mice, and the expression of general and brown adipocyte markers was assessed after 4 weeks. Fibro/adipogenic progenitors (FAPs) and myogenic progenitors were prospectively isolated using fluorescence‐activated cell sorting from skeletal muscle of male and female C57Bl6/6J and Sv/129 mice, and monoclonal and polyclonal cultures were treated with brown adipogenic medium. Additionally, FAPs were differentiated with medium supplemented or not with triiodothyronine.ResultsAlthough skeletal muscle expression of uncoupling protein 1 (Ucp1) was barely detectable in uninjected tibialis anterior muscle, it was drastically induced following intramuscular adipogenesis in Sv/129 mice and further increased in response to beta 3‐adrenergic stimulation. Intramuscular Ucp1 expression did not depend on IL‐6 and was preserved in aged skeletal muscle. Myogenic progenitors did not form adipocytes neither in polyclonal nor monoclonal cultures. Fibro/adipogenic progenitors, on the other hand, readily differentiated into brown‐like, UCP1+ adipocytes. Uncoupling protein 1 expression in differentiated FAPs was regulated by genetic background, sex, and triiodothyronine treatment independently of adipogenic differentiation levels.ConclusionsIntramuscular adipogenesis is associated with increased Ucp1 expression in skeletal muscle from obesity‐resistant mice. Fibro/adipogenic progenitors provide a likely source for intramuscular adipocytes expressing UCP1 under control of both genetic and hormonal factors. Therefore, FAPs constitute a possible target for therapies aiming at the browning of intramuscular adipose tissue and the metabolic improvement of skeletal muscle affected by fatty infiltration.

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“…8 Over the past several years, the field of brown and beige fat biology has seen an increase in the number of reports implicating various growth factors and cytoskeleton dynamics in the regulation of brown and beige fat development. More recently, we and others have demonstrated that beige adipocytes arise from a smooth-muscle origin, 10,12 suggesting that morphogenetic signals may regulate a cell fate switch between smooth muscle cells and beige adipocytes. In this review, we will focus on the effects of morphogens on cell shape and cytoskeleton dynamics.…”

Section: Introductionmentioning

confidence: 87%

Morphogenetics in brown, beige and white fat development

Lin

Farmer

2016

Adipocyte

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Brown and beige (or brite) fat cells are capable of evoking non-shivering thermogenesis in response to cold and b-adrenergic stimulation. By metabolizing lipids and carbohydrate via uncoupled respiration these cells directly convert energy to heat. The discovery of brown and brown-like adipocytes in adult humans has reinvigorated interest in stimulating brown and beige fat development to combat the obesity epidemic. This review focuses on the role that cytoskeleton dynamics play in the regulation of adipocyte biology, specifically beige and brown fat development and how newly discovered adipogenic morphogens affect these processes.

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A Smooth Muscle-Like Origin for Beige Adipocytes

Cited by 403 publications

References 50 publications

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Morphogenetics in brown, beige and white fat development

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