Zfp423 Expression Identifies Committed Preadipocytes and Localizes to Adipose Endothelial and Perivascular Cells

Gupta, Rana K.; Mepani, Rina J.; Kleiner, Sandra; Lo, James C.; Khandekar, Melin J.; Cohen, Paul; Frontini, Andrea; Bhowmick, Diti Chatterjee; Li, Ye; Cinti, Saverio; Spiegelman, Bruce M.

doi:10.1016/j.cmet.2012.01.010

Cited by 367 publications

(314 citation statements)

References 66 publications

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“…Despite contrasting findings from different laboratories (60) our data, including lineage-tracing studies, seem to indicate that endothelial cells of adipose tissue capillaries are able to turn into pericytes and then into either white and brown adipocytes (61,62,63,64,65,66). Such unique origin could support their ability to undergo multiple changes before achievement of the adult phenotype.…”

Section: European Journal Of Endocrinologymentioning

confidence: 76%

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

Giordano

Smorlesi

Frontini

et al. 2014

European Journal of Endocrinology

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221

177

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In mammals, adipocytes are lipid-laden cells making up the parenchyma of the multi-depot adipose organ. White adipocytes store lipids for release as free fatty acids during fasting periods; brown adipocytes burn glucose and lipids to maintain thermal homeostasis. A third type of adipocyte, the pink adipocyte, has recently been characterised in mouse subcutaneous fat depots during pregnancy and lactation. Pink adipocytes are mammary gland alveolar epithelial cells whose role is to produce and secrete milk. Emerging evidence suggests that they derive from the transdifferentiation of subcutaneous white adipocytes. The functional response of the adipose organ to a range of metabolic and environmental challenges highlights its extraordinary plasticity. Cold exposure induces an increase in the 'brown' component of the organ to meet the increased thermal demand; in states of positive energy balance, the 'white' component expands to store excess nutrients; finally, the 'pink' component develops in subcutaneous depots during pregnancy to ensure litter feeding. At the cell level, plasticity is provided not only by stem cell proliferation and differentiation but also, distinctively, by direct transdifferentiation of fully differentiated adipocytes by the stimuli that induce genetic expression reprogramming and through it a change in phenotype and, consequently function. A greater understanding of adipocyte transdifferentiation mechanisms would have the potential to shed light on their biology as well as inspire novel therapeutic strategies against metabolic syndrome (browning) and breast cancer (pinking).

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Section: European Journal Of Endocrinologymentioning

confidence: 76%

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

Giordano

Smorlesi

Frontini

et al. 2014

European Journal of Endocrinology

Self Cite

221

177

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“…Isolation of adipose SV fraction and differentiation of primary adipocytes was done as described previously (50). Oil red O staining was performed as described previously (51).…”

Section: Methodsmentioning

confidence: 99%

Development of insulin resistance in mice lacking PGC-1α in adipose tissues

Kleiner

Mepani

Laznik

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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262

209

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Reduced peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression and mitochondrial dysfunction in adipose tissue have been associated with obesity and insulin resistance. Whether this association is causally involved in the development of insulin resistance or is only a consequence of this condition has not been clearly determined. Here we studied the effects of adipose-specific deficiency of PGC-1α on systemic glucose homeostasis. Loss of PGC-1α in white fat resulted in reduced expression of the thermogenic and mitochondrial genes in mice housed at ambient temperature, whereas gene expression patterns in brown fat were not altered. When challenged with a high-fat diet, insulin resistance was observed in the mutant mice, characterized by reduced suppression of hepatic glucose output. Resistance to insulin was also associated with an increase in circulating lipids, along with a decrease in the expression of genes regulating lipid metabolism and fatty acid uptake in adipose tissues. Taken together, these data demonstrate a critical role for adipose PGC-1α in the regulation of glucose homeostasis and a potentially causal involvement in the development of insulin resistance.glucose metabolism | mitochondrial gene expression | thermogenesis | cold exposure | type 2 diabetes

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“…Using lineage tracing, Zfp423 has recently been identified as a factor playing a key role in the early commitment of both brown and white fat. Zpf423 is easily detected in both BAT and WAT preadipocyte depots in the adipose vasculature, coinciding with a subset of pericytes (Gupta et al 2012), suggesting once again a possible endothelial origin of fat. In an independent study, WAT precursors in adipose vasculature were also identified by Tang et al (2008).…”

Section: Bat Precursors In Adult Mice: Endothelial and Other Originsmentioning

confidence: 99%

Adipogenesis: new insights into brown adipose tissue differentiation

Carobbio

Rosen

Vidal-Puig

2013

Journal of Molecular Endocrinology

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Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models both in vivo and in vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.

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Zfp423 Expression Identifies Committed Preadipocytes and Localizes to Adipose Endothelial and Perivascular Cells

Cited by 367 publications

References 66 publications

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

Development of insulin resistance in mice lacking PGC-1α in adipose tissues

Adipogenesis: new insights into brown adipose tissue differentiation

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