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Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3's expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids. [ABSTRACT FROM AUTHOR]

Aging is associated with increased adiposity and diminished thermogenesis, but the critical transcription factors influencing these metabolic changes late in life are poorly understood. We recently demonstrated that the winged helix factor forkhead box protein A3 (Foxa3) regulates the expansion of visceral adipose tissue in high-fat diet regimens; however, whether Foxa3 also contributes to the increase in adiposity and the decrease in brown fat activity observed during the normal aging process is currently unknown. Here we report that during aging, levels of Foxa3 are significantly and selectively up-regulated in brown and inguinal white fat depots, and that midage Foxa3-null mice have increased white fat browning and thermogenic capacity, decreased adipose tissue expansion, improved insulin sensitivity, and increased longevity. Foxa3 gain-of-function and loss-of-function studies in inguinal adipose depots demonstrated a cell-autonomous function for Foxa3 in white fat tissue browning. Furthermore, our analysis revealed that the mechanisms of Foxa3 modulation of brown fat gene programs involve the suppression of peroxisome proliferator activated receptor γ coactivtor 1 α (PGC1α) levels through interference with cAMP responsive element binding protein 1-mediated transcriptional regulation of the PGC1α promoter. Overall, our data demonstrate a role for Foxa3 in energy expenditure and in age-associated metabolic disorders. [ABSTRACT FROM AUTHOR]

In this paper, an empirical study on the correlation between housing prices, bank credit and inflation is conducted through impulse response analysis and variance decomposition with 158 groups of monthly data from January 2000-July 2014 as the samples. The research findings show that: the expansion of inflation and bank credit can stimulate the rise of housing prices in the short term; the expansion of bank credit can curb inflation, and the rise of housing prices can curb inflation in the short term; inflation has positive stimulation on bank credit in the short term, and the rise of housing prices can stimulate the expansion of bank credit in the short term. [ABSTRACT FROM AUTHOR]

Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a small interfering RNA (siRNA) screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBPβ and -δ to transcriptionally induce PPARγ expression. Furthermore, we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPARγ specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall, our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion. [ABSTRACT FROM AUTHOR]

Purpose There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in T-LBL. Materials and Methods Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test. Results The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001). Conclusion Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression. [ABSTRACT FROM AUTHOR]

Sphingolipids are a diverse class of essential cellular lipids that function as structural membrane components and as signaling molecules. Cells acquire sphingolipids by both de novo biosynthesis and recycling of exogenous sphingolipids. The individual importance of these pathways for the generation of essential sphingolipids in differentiated cells is not well understood. To investigate the requirement for de novo sphingolipid biosynthesis in adipocytes, a cell type with highly regulated lipid metabolism, we generated mice with an adipocyte-specific deletion of Sptlc1. Sptlc1 is an obligate subunit of serine palmitoyltransferase, the enzyme responsible for the first and rate-limiting step of de novo sphingolipid biosynthesis. These mice, which initially developed adipose tissue, exhibited a striking age-dependent loss of adipose tissue accompanied by evidence of adipocyte death, increased macrophage infiltration, and tissue fibrosis. Adipocyte differentiation was not affected by the Sptlc1 deletion. The mice also had elevated fasting blood glucose, fatty liver, and insulin resistance. Collectively, these data indicate that de novo sphingolipid biosynthesis is required for adipocyte cell viability and normal metabolic function and that reduced de novo sphingolipid biosynthesis within adipocytes is associated with adipocyte death, adipose tissue remodeling, and metabolic dysfunction. [ABSTRACT FROM AUTHOR]