Seale, P., Kajimura, S. & Spiegelman, B. M. Transcriptional control of brown adipocyte development and physiological function-of mice and men. Genes Dev. 23, 788-797

Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes & development (Impact Factor: 10.8). 05/2009; 23(7):788-97. DOI: 10.1101/gad.1779209
Source: PubMed


The last several years have seen an explosion of information relating to the transcriptional control of brown fat cell development. At the same time, new data have emerged that clearly demonstrate that adult humans do indeed have substantial amounts of functioning brown adipose tissue (BAT). Together, these advances are stimulating a reassessment of the role of brown adipose tissue in human physiology and pathophysiology. These data have also opened up exciting new opportunities for the development of entirely novel classes of therapeutics for metabolic diseases like obesity and type 2 diabetes.

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Available from: Shingo Kajimura, Jan 27, 2014
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    • "It appears as discrete brown fat depots during foetal development and as diffuse populations in traditional white fat depots during post-natal development , which can be induced by adrenergic stimulation (Frontini and Cinti, 2010). Recently, the transcriptional control and development of BAT have attracted substantial interest (Seale et al., 2009). However, it remains unknown whether BAT can play a role in combating obesity. "
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    • "These “beige” adipocytes originate from progenitor pools that are developmentally distinct from brown adipocytes in BAT [10], [11]. Several transcriptional factors and cofactors have been identified to regulate different aspects of brown fat development, including Prdm16, C/EBPβ, Foxc2, Twist1, PGC-1α and PGC-1β [10], [12], [13], [14], [15], [16], [17], [18]. "
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    ABSTRACT: The biological clock plays an important role in integrating nutrient and energy metabolism with other cellular processes. Previous studies have demonstrated that core clock genes are rhythmically expressed in peripheral tissues, including the liver, skeletal muscle, pancreatic islets, and white and brown adipose tissues. These peripheral clocks are entrained by physiological cues, thereby aligning the circadian pacemaker to tissue functions. The mechanisms that regulate brown adipose tissue clock in response to physiological signals remain poorly understood. Here we found that the expression of core clock genes is highly responsive to cold exposure in brown fat, but not in white fat. This cold-inducible regulation of the clock network is mediated by adrenergic receptor activation and the transcriptional coactivator PGC-1α. Brown adipocytes in mice lacking a functional clock contain large lipid droplets accompanied by dysregulation of genes involved in lipid metabolism and adaptive thermogenesis. Paradoxically, the "clockless" mice were competent in maintaining core body temperature during cold exposure. These studies elucidated the presence of adrenergic receptor/clock crosstalk that appears to be required for normal thermogenic gene expression in brown fat.
    PLoS ONE 08/2013; 8(8):e70109. DOI:10.1371/journal.pone.0070109 · 3.23 Impact Factor
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    • "Current investigations are focused on elucidating the mechanisms, adipose tissue-secreted factors, and developmental signals that account for regional differences in WAT development and function. It is important to note that the developmental origin of white and brown adipose tissue is distinct (reviewed in [25] [26]), and the physiological role of brown fat in human body weight regulation and obesity-associated metabolic complications is controversial and has not been elucidated (reviewed in [27]). This review will provide an overview of the depot-and sex-dependent differences in important functions of white adipose tissue, such as adipogenesis, expression of developmental patterning transcription factors, the storage and release of fatty acids, and secretory function. "
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    ABSTRACT: Obesity, characterized by excessive adiposity, is a risk factor for many metabolic pathologies, such as Type 2 Diabetes mellitus (T2DM). Numerous studies have shown that adipose tissue distribution may be a greater predictor of metabolic health. Upper-body fat (visceral and subcutaneous abdominal) is commonly associated with the unfavorable complications of obesity, while lower-body fat (gluteal-femoral) may be protective. Current research investigations are focused on analyzing the metabolic properties of adipose tissue, in order to better understand the mechanisms that regulate fat distribution in both men and women. This review will highlight the adipose tissue depot- and sex- dependent differences in white adipose tissue function, including adipogenesis, adipose tissue developmental patterning, the storage and release of fatty acids, and secretory function. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.
    Biochimica et Biophysica Acta 05/2013; 1842(3). DOI:10.1016/j.bbadis.2013.05.006 · 4.66 Impact Factor
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