Article

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

Department of Molecular and Cell Biology, Harvard University, Cambridge, Massachusetts, United States
Genes & development (Impact Factor: 10.8). 05/2009; 23(7):788-97. DOI: 10.1101/gad.1779209
Source: PubMed

ABSTRACT

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.

Download full-text

Full-text

Available from: Shingo Kajimura, Jan 27, 2014
  • Source
    • "In rodents and newborn humans, white and brown adipose tissue (WAT and BAT, respectively) represent two distinct types of adipose tissue with different morphologies and functions (Cinti 2012). Whereas WAT is deputed to store energy in the form of triglycerides, the BAT function is to burn fat and convert chemical energy into heat for thermogenesis (Seale et al. 2009, Cinti 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity.
    Preview · Article · Aug 2015 · Journal of Molecular Endocrinology
  • Source
    • "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. "

    Full-text · Dataset · Dec 2013
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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.
    Preview · Article · Aug 2013 · PLoS ONE
Show more