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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299609PMC
http://dx.doi.org/10.1038/srep42130DOI Listing

Publication Analysis

Top Keywords

brown adipogenic
8
brown fat
8
fat cell
8
cell differentiation
8
brown
5
dissecting brown
4
adipogenic regulatory
4
regulatory network
4
network integrative
4
integrative genomics
4

Similar Publications

A spontaneously immortalized muscle stem cell line (EfMS) from brown-marbled grouper for cell-cultured fish meat production.

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 PDF

Bisphenol A and its metabolites promote white adipogenesis and impair brown adipogenesis in vitro.

Toxicology

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 PDF

Whole transcriptome sequencing analysis reveals the effect of circZFYVE9/miR-378a-3p/IMMT axis on mitochondrial function in adipocytes.

Int 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 PDF

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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!