Brown adipocytes regulate energy expenditure via mitochondrial uncoupling, which makes them attractive therapeutic targets to tackle obesity. However, the regulatory mechanisms underlying brown adipogenesis are still poorly understood. To address this, we profiled the transcriptome and chromatin state during mouse brown fat cell differentiation, revealing extensive gene expression changes and chromatin remodeling, especially during the first day post-differentiation. To identify putatively causal regulators, we performed transcription factor binding site overrepresentation analyses in active chromatin regions and prioritized factors based on their expression correlation with the bona-fide brown adipogenic marker Ucp1 across multiple mouse and human datasets. Using loss-of-function assays, we evaluated both the phenotypic effect as well as the transcriptomic impact of several putative regulators on the differentiation process, uncovering ZFP467, HOXA4 and Nuclear Factor I A (NFIA) as novel transcriptional regulators. Of these, NFIA emerged as the regulator yielding the strongest molecular and cellular phenotypes. To examine its regulatory function, we profiled the genomic localization of NFIA, identifying it as a key early regulator of terminal brown fat cell differentiation.
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http://dx.doi.org/10.1038/srep42130 | DOI Listing |
Commun Biol
December 2024
MOE Key Laboratory of Marine Genetics & Breeding and College of Marine Life Sciences, Ocean University of China, Qingdao, China.
Lacking of suitable fish muscle stem cell line has greatly hindered the fabrication of cell-cultured fish meat. Here, we established and characterized a spontaneously immortalized marine fish muscle stem cell line (EfMS) from brown-marbled grouper (Epinephelus fuscoguttatus), which could actively proliferate with good genetic stability and well maintain the stemness of myogenesis potential for over 50 passages. Taurine was found to be able to serve as a substitute of fish muscle extract in maintaining stemness.
View Article and Find Full Text PDFToxicology
December 2024
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing, China. Electronic address:
Bisphenol A (BPA), an obesogen, can disrupt adipogenesis in vitro, but these studies did not distinguish adipocytes as white or brown. BPA can be metabolized into BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). These metabolites are not completely inactive in the body, but the related studies remain limited.
View Article and Find Full Text PDFInt J Biol Macromol
November 2024
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:
Recent research highlights the complex regulation of lipid accumulation and mitochondrial function in adipocytes via non-coding RNAs like microRNAs and circular non-coding RNAs. Circular non-coding RNAs act as endogenous regulators, impacting lipid metabolism and mitochondrial function by interacting with miRNAs. Sequencing white and brown adipose tissues in mice revealed significant variations in 1936 mRNAs, 127 miRNAs, and 171 circRNAs.
View Article and Find Full Text PDFMicrobiome
October 2024
Department of Animal Science, College of Animal Sciences, Zhejiang University, Hangzhou, 310030, PR China.
Background: Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important.
View Article and Find Full Text PDFBMC Genomics
October 2024
Grassland & Cattle Investment Co., Ltd, Hohhot, 011500, China.
Background: Mongolian cattle are local breeds in northern China with excellent adaptability to harsh environmental conditions. Adipose tissues play essential roles in tolerance to cold and disease, but the associated cellular and molecular mechanisms are unclear.
Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed on the adipose tissues from the subcutaneous (SAT), greater omentum (OAT) and perirenal (PAT) of 3 healthy cattle.
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