Transcriptional control of brown adipocyte differentiation and function by NFIA: recent perspectives on deciphering metabolic diseases.

J Biochem

Laboratory for Advanced Research on Pathophysiology of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Published: September 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Brown adipocytes dissipate chemical energy as heat and confer protection against type 2 diabetes and obesity. Nuclear factor I-A (NFIA) is a transcription factor that orchestrates the brown fat gene programme by activating cell type-specific enhancers and facilitating the genomic binding of PPARγ, the master regulator of adipogenesis, to these enhancers. NFIA promotes mitochondrial oxidative phosphorylation and thermogenesis, while reciprocally suppressing adipose tissue inflammation, thereby contributing to the maintenance of glucose and body weight homeostasis in mice. Here the author provides an overview of the identification of NFIA as a pivotal regulator of brown adipocyte biology, elucidates its underlying mechanisms of action, examines its implications for systemic metabolism and outlines future perspectives for research in this field.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372464PMC
http://dx.doi.org/10.1093/jb/mvaf038DOI Listing

Publication Analysis

Top Keywords

brown adipocyte
8
transcriptional control
4
brown
4
control brown
4
adipocyte differentiation
4
differentiation function
4
nfia
4
function nfia
4
nfia perspectives
4
perspectives deciphering
4

Similar Publications

Cyclic nucleotides are critical regulators of adaptive thermogenesis and adipogenesis, with their intracellular levels finely tuned by phosphodiesterases. Phosphodiesterase type 5 (PDE5A) modulates cyclic guanosine monophosphate (cGMP) levels in adipocytes. While PDE5A inhibition has shown promise in patients with diabetes, its role in metabolism remains unclear.

View Article and Find Full Text PDF

Brown adipose tissue (BAT) plays a key role in metabolic homeostasis through its thermogenic effects and the secretion of regulatory molecules. Here we report that RAP250 haploinsufficiency stimulates BAT in mice, thus contributing to a decrease in fat accumulation. Local in vivo AAV-mediated RAP250 silencing in BAT reduces body weight and fat mass and enhances glucose oxidation, thereby indicating that RAP250 participates in the regulation of BAT metabolic activity.

View Article and Find Full Text PDF

FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes.

Obesity (Silver Spring)

September 2025

Fraternal Order of Eagles Diabetes Research Center and Department of Internal Medicine, Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

Objective: Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet-induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.

Methods: We generated mice simultaneously lacking the Opa1, Fgf21, and Gdf15 genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high-fat diet feeding.

View Article and Find Full Text PDF

Brazilian Green Propolis Regulates Thermogenesis via Two Distinct Pathways.

J Nutr Sci Vitaminol (Tokyo)

August 2025

College of Bioscience and Biotechnology and Graduate School of Bioscience and Biotechnology, Chubu University.

Brazilian green propolis (BGP), produced by honey bees, induces beige adipocyte formation and accelerates whole-body energy metabolism. Artepillin C (ArtC), the major cinnamic acid derivative of BGP, induces beige adipocyte formation and increases thermogenesis in inguinal white adipose tissue. However, the effects of BGP on beige adipocyte formation and energy metabolism remain unclear.

View Article and Find Full Text PDF

Suppression of adipocyte ABHD6 favors anti-inflammatory and adipogenic programs to preserve adipose tissue fitness in obesity.

Mol Metab

August 2025

Montreal Diabetes Research Center - Centre de Recherche du Centre Hospitalier de l'Université de Montréal, and departments of Nutrition and Biochemistry, University of Montreal, Montreal, Canada. Electronic address:

Some individuals exhibit metabolically healthy obesity, characterized by the expansion of white adipose tissue (WAT) without associated complications. The monoacylglycerol (MAG) hydrolase α/β-hydrolase domain-containing 6 (ABHD6) has been implicated in energy metabolism, with its global deletion conferring protection against obesity. However, the immunometabolic roles of adipocyte ABHD6 in WAT remodeling in response to nutri-stress and obesity are not known.

View Article and Find Full Text PDF