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Judy Tsai
Publications and source records attributed to Judy Tsai.
The transcription factor GATA2 regulates differentiation of brown adipocytes.
Brown adipose tissue (BAT) is a specialized mammalian tissue and a site of adaptive thermogenesis. Although the metabolic functions of brown and white adipocytes are distinct, terminal differentiation of both adipocyte lineages is regulated by well-characterized common transcription factors. However, the early stages of adipocyte differentiation and regulation of precursor cells are not well understood. We report here that GATA2 is expressed in brown adipocyte precursors, and its expression is downregulated in a differentiation-dependent manner. Constitutive expression of GATA2 suppressed expression of BAT-specific genes in brown adipocytes, whereas disruption of a GATA2 allele in brown preadipocytes resulted in significantly elevated differentiation and expression of several markers of brown adipogenesis. Collectively, these results show that GATA2 functions to suppress brown adipocyte differentiation, whereas reduction of GATA2 promotes brown adipogenesis.
Adipogenesis↗
Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation.
We have previously demonstrated that GATA-2 and GATA-3 are expressed in adipocyte precursors and control the preadipocyte-to-adipocyte transition. Constitutive expression of both GATA-2 and GATA-3 suppressed adipocyte differentiation, partially through direct binding to the peroxisome proliferator-activated receptor gamma (PPARgamma) promoter and suppression of its basal activity. In the present study, we demonstrate that both GATA-2 and GATA-3 form protein complexes with CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta, members of a family of transcription factors that are integral to adipogenesis. We mapped this interaction to the basic leucine zipper domain of C/EBPalpha and a region adjacent to the carboxyl zinc finger of GATA-2. The interaction between GATA and C/EBP factors is critical for the ability of GATA to suppress adipocyte differentiation. Thus, these results show that in addition to its previously recognized function in suppressing PPARgamma transcriptional activity, interaction of GATA factors with C/EBP is necessary for their ability to negatively regulate adipogenesis.
Adipocytes↗
Cardio-respiratory measures following isocapnic voluntary hyperventilation.
In some individuals, breathing is greater than at rest following voluntary hyperventilation. Most previous investigations have employed short hyperventilation periods; here we examine the time course of cardio-respiratory measures before, during, and after a 5-min voluntary hyperventilation, maintaining isocapnia throughout. We examined the possible co-involvement of the cardiovascular system; hypothesising that post-hyperventilation hyperpnoea results from an increase in autonomic arousal. In four subjects (two males, two females) of 18 (nine males, nine females) we observed a post-hyperventilation hyperpnoea, characterised by a slow decline of ventilation toward resting levels with a time constant of 109.0 +/- 16.1s. By contrast, heart rate, and systolic and diastolic blood pressure were unchanged from rest during and after voluntary hyperventilation for all subjects. We concluded that males and females were equally likely to exhibit post-hyperventilation hyperpnoea, and suggest that they may be characterised by an increased resting heart rate and the choice of breathing frequency to increase ventilation during the voluntary hyperventilation. We further concluded that post-hyperventilation hyperpnoea is rare, but when present is a strong and lasting phenomenon, and that it is not the result of an increased autonomic arousal.
Adult↗
GATA transcription factors and fat cell formation.
GATA transcription factors play important roles in a variety of developmental processes. Recently, we discovered that GATA factors also play a key role in adipogenesis. Two isoforms, GATA-2 and GATA-3, are specifically expressed in murine preadipocytes but not mature adipocytes. Continuous expression of GATA factors in preadipocyte cell lines inhibits terminal differentiation into mature adipocytes. In contrast, GATA-3-deficient mouse embryonic stem cells possess a higher capacity to convert to adipocytes. The inhibitory effect of GATA on adipogenesis is mediated in part by suppression of promoters of adipogenic factors, including peroxisome proliferator-activated receptor gamma, but additional mechanisms are also likely to be in effect. These findings indicate that GATA factors function as molecular gatekeepers at the onset of terminal adipocyte differentiation. Whether GATA factors are also involved in the commitment of multipotent mesenchymal stem cells to progenitors of the adipogenic lineage is under investigation.
Adipocytes↗