Project description:In order to provide more evidence to prove that BCAAs catabolism mediates the expressions of FASN and ACLY by altering histone acetylation in melanoma, ChIP-seq of xenografted A2058 tumors implanted in mice receiving BCAA dietary interventions (normal or high BCAA diet) was employed to idenfity the enrichment of histone acetylation on the promoter of FASN and ACLY.
Project description:Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a novel transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the adipogenic master regulator, PPARgamma, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARgamma, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts results in brown adipocyte differentiation. Conversely, the brown fat of NFIA knockout mice displays impaired expression of the brown-fat-specific genes and reciprocal elevation of muscle genes. Finally, expression of NFIA and the brown-fat-specific genes is positively correlated in human brown fat. These results indicate that NFIA is a key transcriptional regulator of brown fat and exerts its effects by co-localizing with PPARg at cell-type-specific enhancers.
Project description:We identify distinct murine brown adipocytes lineages using bioinformatics analysis of gene expression profiles generated by RNAseq. Further comparison with established-database for human and mouse brown fat genes enables us to sort and determine three genes to distinguish different lineages.
Project description:We report the RNA expression of the mature brown fat from 6 week old wild type (WT) and PHOSPHO1 knockout (KO) mice. Mature brown fat was isolated from brown adipose tissue after collagenase digestion. Increased expression of mitochondrial genes is found in KO brown fat.
Project description:Analysis of brown adipose tissue from Yin Yang 1 (YY1) brown fat specific knockout mice fed a high fat diet for 3 months. YY1 deficiency in brown adipose tissue leads to strong thermogenic deficiency. The goal was to identify the genes controlled by YY1 responsible of brown fat defective function.
Project description:Analysis of brown adipose tissue from Yin Yang 1 (YY1) brown fat specific knockout mice fed a high fat diet for 3 months. YY1 deficiency in brown adipose tissue leads to strong thermogenic deficiency. The goal was to identify the genes controlled by YY1 responsible of brown fat defective function. Control mice YY1flox/flox versus YY1flox/flox; Ucp1Cre were fed a high fat diet for 3 months
Project description:ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in non-alcoholic fatty liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol lowering drug bempedoic acid (BPA), which has been shown to improve steatosis in mice. However, the acetyl-CoA synthetase ACSS2 can compensate for ACLY deficiency to support DNL, potentially complicating the targeting of ACLY. We show that hepatic loss of both ACLY and ACSS2 reduces DNL. Nevertheless, even when ACSS2 is suppressed by dietary or genetic means, we find that steatosis is counterintuitively exacerbated with hepatic ACLY deficiency in mice fed a Western diet (WD), linked to reduced expression of PPARa target genes controlling fatty acid oxidation. Conversely, BPA treatment increased fat catabolism and ameliorated WD-mediated lipid accumulation in both WT and liver ACLY knockout mice. Thus, hepatic ACLY plays an unexpected role in restraining diet-dependent lipid accumulation, and BPA improves steatosis independent of ACLY.
Project description:Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a novel transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the adipogenic master regulator, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts results in brown adipocyte differentiation. Conversely, the brown fat of NFIA knockout mice displays impaired expression of the brown-fat-specific genes and reciprocal elevation of muscle genes. Finally, expression of NFIA and the brown-fat-specific genes is positively correlated in human brown fat. These results indicate that NFIA is a key transcriptional regulator of brown fat and exerts its effects by co-localizing with PPARγ at cell-type-specific enhancers.
Project description:To study the role of Ybx2 in brown fat activity, we performed the RNA-seq data for wildtype and Ybx2 knockout brown fat under room temperature and upon cold exposure as well as for wildtype and Ybx2 knockout brown adipocytes culture from stromal vascular fraction cells. To determine the targets of Ybx2, we performed RNA immunopercipitatoin followed by RNA-seq
Project description:T cell activation is known to require a metabolic shift towards glycolysis, triggered by TCR-engagement . To evaluate the role of ACLY or PDH in transcriptional reprogramming. T cell-specific Pdha1 knockout mouse by crossing Pdha1fl/fl mouse with CD4CreERT2 and CD4+ T cells from conditional knockout mice with T cell-specific ablation of Acly (CD4-Cre Aclyfl/fl).
