Adipose-specific BMP and activin membrane-bound inhibitor (BAMBI) deletion promotes adipogenesis by accelerating ROS production

J Biol Chem. 2021 Jan-Jun:296:100037. doi: 10.1074/jbc.RA120.014793. Epub 2020 Nov 23.

Abstract

With the improvement of people's living standards, the number of obese patients has also grown rapidly. It is reported that the level of oxidative stress in obese patients has significantly increased, mainly caused by the increase in reactive oxygen species (ROS) levels in adipose tissue. Studies have shown that the use of siRNA to interfere with bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression could promote adipocyte differentiation, and under hypoxic conditions, BAMBI could act as a regulator of HIF1α to regulate the polarity damage of epithelial cells. In view of these results, we speculated that BAMBI may regulate adipogenesis by regulating the level of ROS. In this study, we generated adipose-specific BAMBI knockout mice (BAMBI AKO) and found that compared with control mice, BAMBI AKO mice showed obesity when fed with high-fat diet, accompanied by insulin resistance, glucose intolerance, hypercholesterolemia, and increased inflammation in adipose tissue. Interestingly, adipose-specific deficiency of BAMBI could cause an increase in the expression level of Nox4, thereby promoting ROS production in cytoplasm and mitochondria and the DNA-binding activity of C/EBPβ and ultimately promoting adipogenesis. Consistently, our findings indicated that BAMBI may be a reactive oxygen regulator to affect adipogenesis, thereby controlling obesity and metabolic syndrome.

Keywords: BAMBI; NADPH oxidase 4; ROS production; adipogenesis; insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Adipogenesis*
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism*
  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Diet, High-Fat
  • Fatty Liver / genetics
  • Humans
  • Insulin Resistance / genetics
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Knockout
  • Reactive Oxygen Species / metabolism*

Substances

  • BAMBI protein, human
  • Bone Morphogenetic Proteins
  • CCAAT-Enhancer-Binding Protein-beta
  • CEBPB protein, human
  • Membrane Proteins
  • Reactive Oxygen Species
  • Acetylcysteine