Short-chain fatty acids (SCFAs), particularly acetate, propionate and butyrate, are mainly produced by anaerobic fermentation of gut microbes. SCFAs play an important role in regulating energy metabolism and energy supply, as well as maintaining the homeostasis of the intestinal environment. In recent years, many studies have shown that SCFAs demonstrate physiologically beneficial effects, and the signalling pathways related to SCFA production, absorption, metabolism, and intestinal effects have been discovered. Two major signalling pathways concerning SCFAs, G-protein-coupled receptors (GPRCs) and histone deacetylases (HDACs), are well recognized. In this review, we summarize the recent advances concerning the biological properties of SCFAs and the signalling pathways in inflammation and glucose and lipid metabolism.
S-phase transcription of the histone 2B (H2B) gene is dependent on Octamer-binding factor 1 (Oct-1) and Oct-1 Co-Activator in S-phase (OCA-S), a protein complex comprising glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase (p38/GAPDH and p36/LDH) along with other components. H2B transcription in vitro is modulated by NAD(H). This potentially links the cellular redox status to histone expression. Here, we show that H2B transcription requires a proper NAD ؉ / NADH redox status in vitro and in vivo. Therefore, perturbing a properly balanced redox impairs H2B transcription. A redoxmodulated direct p38/GAPDH-Oct-1 interaction nucleates the occupancy of the H2B promoter by the OCA-S complex, in which p36/LDH plays a critical role in the hierarchical organization of the complex. As for p38/GAPDH, p36/LDH is essential for the OCA-S function in vivo, and OCA-S-associated p36/ LDH possesses an LDH enzyme activity that impacts H2B transcription. These studies suggest that the cellular redox status (metabolic states) can directly feedback to gene switching in higher eukaryotes as is commonly observed in prokaryotes.S-phase progression requires cyclin E/cdk2 signaling, which orchestrates coupled DNA replication and histone expression. This is mediated by NPAT, i.e. nuclear protein, the ataxia-telangiectasia locus, a cyclin E/cdk2 substrate (1-3). Transcription of histone genes is mediated by subtype-specific promoter elements and associated transcription factors and/or co-activators (4 -6), and the overall histone expression levels are regulated post-transcriptionally as well (5). In addition, the histone expression is highly coordinated (4) and is tightly coupled to S-phase progression (7).The transcription of the histone 2B (H2B) gene depends on Octamer-binding factor 1 (Oct-1) 5 and Oct-1 Co-Activator in S-phase (OCA-S), a co-activator complex comprising the glycolytic enzymes p38/GADPH and p36/LDH among other subunits (4, 5, 8 -11). Oct-1 binds the essential octamer site in the H2B promoter throughout the interphase; however, OCA-S occupies the H2B promoter only in the S-phase (10). A direct Oct-1-p38/GAPDH interaction and H2B transcription are modulated by NAD(H) in vitro (10). This implicates a redoxmodulated H2B expression in vivo and potentially links the redox status (metabolic states) of the cell to gene switching. Quite common in prokaryotes, such links have been rarely reported in higher eukaryotes (12).Here, we provide evidence that a proper NAD ϩ /NADH redox status (ratio) is important for optimal H2B expression both in vitro and in vivo. The direct Oct-1-p38/GAPDH interaction plays a role nucleating the H2B promoter occupancy by OCA-S, which dictates the redox-modulated H2B transcription. p36/LDH is also essential for H2B expression in vivo and plays a critical role in the hierarchical organization of OCA-S. Finally, the OCA-S-associated p36/LDH possesses an intrinsic catalytic activity that exerts an impact upon H2B transcription. Our studies suggest that the nuclear moonlighting transcription...
Genistein may regulate lipid metabolism in adipose tissue of obese mice by regulating the expression of miR-222 and its target genes, BTG2 and adipor1.
The development of skeletal muscle is a complex process including myoblasts proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at post-transcriptional level. Increasing evidences indicate that miRNAs are important regulators in myogenic processes. Here, we reported that the expression of miR-10b-5p steadily decreased during myoblasts proliferation, but significantly increased during myoblasts differentiation. The over-expression of miR-10b-5p promoted myoblasts proliferation and blunted myofiber formation in C2C12 cells, while miR-10b-5p down-regulation showed an opposite result. At the same time, we observed that the down-regulation of nuclear factor of activated T-cells 5 (NFAT5) repressed the differentiation of C2C12 cells, and interestingly, miR-10b-5p could suppress NFAT5 expression. Luciferase activity assays confirmed that miR-10b-5p directly target the 3ʹ-untranslated region (3ʹ-UTR) of NFAT5. Overall, we proposed here a novel insight that miR-10b-5p regulates the proliferation and differentiation of C2C12 myoblasts, and the impact on myogenic differentiation is partly through targeting NFAT5.
Abbreviations: NFAT5: nuclear factor of activated T-cells 5; Cyclin B: cycle protein B; Cyclin D1: cycle protein D1; Cyclin E: cycle protein E; CDK4: cyclin-dependent kinase 4; MyoD: myogenic differentiation antigen; MyoG: myogenin; Myf5: myogenic factor 5; MRF4: myogenic regulatory factor 4; MyHC: myosin heavy chain; AQP5: aquaporin-5; CACNA1C: calcium voltage-gated channel subunit alpha1 C; SRF: serum response factor; Pax7: paired box 7; KLF4: Kruppel-like factor 4; 3'-UTR: 3'-untranslated region; GM: growth medium; DM: differentiation medium
Functional differences in the different types of adipose tissue and the impact of their dysfunction on metabolism are associated with the regional distribution of adipose depots. Here we show a genome-wide comparison between the transcriptomes of one source of subcutaneous and two sources of visceral adipose tissue in the pig using an RNA-seq approach. We obtained ~32.3 million unique mapped reads which covered ~80.2% of the current annotated transcripts across these three sources of adipose tissue. We identified various genes differentially expressed between subcutaneous and visceral adipose tissue, which are potentially associated with the inflammatory features of visceral adipose tissue. These results are of benefit for understanding the phenotypic, metabolic and functional differences between different types of adipose tissue that are deposited in different body sites.
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