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

Chen, Xiaochang; Zhao, Chen; Xu, Yanting; Huang, Kuilong; Wang, Yulong; Wang, Xiaoyu; Zhou, Xiaoge; Pang, Wei; Yang, Gongshe; Yu, Taiyong

doi:10.1074/jbc.ra120.014793

Cited by 19 publications

(15 citation statements)

References 38 publications

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“…A recent study showed that adipocyte-specific depletion of BAMBI caused an induction of Nox4 expression in adipose tissue, thereby promoting ROS generation in cytoplasm and mitochondria. The deficiency of BAMBI in adipose tissue resulted in an enhanced DNA-binding activity of C/EBPβ and promoted adipogenesis ( 154 ). These results together suggested that BAMBI may be an important mediator of adipogenesis through regulating ROS.…”

Section: Potential Targets Mediating Oxidative Stress In Adipose Tissmentioning

confidence: 99%

The Interplay Between Adipose Tissue and Vasculature: Role of Oxidative Stress in Obesity

Zhou

Xia

2021

Front. Cardiovasc. Med.

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Cardiovascular diseases (CVDs) rank the leading cause of morbidity and mortality globally. Obesity and its related metabolic syndrome are well-established risk factors for CVDs. Therefore, understanding the pathophysiological role of adipose tissues is of great importance in maintaining cardiovascular health. Oxidative stress, characterized by excessive formation of reactive oxygen species, is a common cellular stress shared by obesity and CVDs. While plenty of literatures have illustrated the vascular oxidative stress, very few have discussed the impact of oxidative stress in adipose tissues. Adipose tissues can communicate with vascular systems, in an endocrine and paracrine manner, through secreting several adipocytokines, which is largely dysregulated in obesity. The aim of this review is to summarize current understanding of the relationship between oxidative stress in obesity and vascular endothelial dysfunction. In this review, we briefly describe the possible causes of oxidative stress in obesity, and the impact of obesity-induced oxidative stress on adipose tissue function. We also summarize the crosstalk between adipose tissue and vasculature mediated by adipocytokines in vascular oxidative stress. In addition, we highlight the potential target mediating adipose tissue oxidative stress.

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Section: Potential Targets Mediating Oxidative Stress In Adipose Tissmentioning

confidence: 99%

The Interplay Between Adipose Tissue and Vasculature: Role of Oxidative Stress in Obesity

Zhou

Xia

2021

Front. Cardiovasc. Med.

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“…Genetic and evolutionary analysis suggests that the increased expression of BMPR2 mRNA in adipose tissue of obese patients has been selected because it is a metabolic “thrifty” gene that is contributing to present day obesity [ 17 ]. Recent studies in mice showed that enhanced BMP activity causes obesity, hyperglycemia, and insulin resistance [ 18 , 19 ]. The mechanism by which overactive BMP signaling contributes to obesity is not known.…”

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein signaling regulation of AMPK and PI3K in lung cancer cells and C. elegans

et al. 2022

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Background Bone morphogenetic protein (BMP) is a phylogenetically conserved signaling pathway required for development that is aberrantly expressed in several age-related diseases including cancer, Alzheimer’s disease, obesity, and cardiovascular disease. Aberrant BMP signaling in mice leads to obesity, suggesting it may alter normal metabolism. The role of BMP signaling regulating cancer metabolism is not known. Methods To examine BMP regulation of metabolism, C. elegans harboring BMP gain-of-function (gof) and loss-of-function (lof) mutations were examined for changes in activity of catabolic and anabolic metabolism utilizing Western blot analysis and fluorescent reporters. AMP activated kinase (AMPK) gof and lof mutants were used to examine AMPK regulation of BMP signaling. H1299 (LKB1 wild-type), A549 (LKB1 lof), and A549-LKB1 (LKB1 restored) lung cancer cell lines were used to study BMP regulation of catabolic and anabolic metabolism. Studies were done using recombinant BMP ligands to activate BMP signaling, and BMP receptor specific inhibitors and siRNA to inhibit signaling. Results BMP signaling in both C. elegans and cancer cells is responsive to nutrient conditions. In both C. elegans and lung cancer cell lines BMP suppressed AMPK, the master regulator of catabolism, while activating PI3K, a regulator of anabolism. In lung cancer cells, inhibition of BMP signaling by siRNA or small molecules increased AMPK activity, and this increase was mediated by activation of LKB1. BMP2 ligand suppressed AMPK activation during starvation. BMP2 ligand decreased expression of TCA cycle intermediates and non-essential amino acids in H1299 cells. Furthermore, we show that BMP activation of PI3K is mediated through BMP type II receptor. We also observed feedback signaling, as AMPK suppressed BMP signaling, whereas PI3K increased BMP signaling. Conclusion These studies show that BMP signaling suppresses catabolic metabolism and stimulates anabolic metabolism. We identified feedback mechanisms where catabolic induced signaling mediated by AMPK negatively regulates BMP signaling, whereas anabolic signaling produces a positive feedback regulation of BMP signing through Akt. These mechanisms were conserved in both lung cancer cells and C. elegans. These studies suggest that aberrant BMP signaling causes dysregulation of metabolism that is a potential mechanism by which BMP promotes survival of cancer cells.

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“…Establishment of the mitochondrial network is the prerequisite for stem cells to differentiate into a functional phenotype (21,22). A previous study showed that interference with the expression of BMP and activin membrane-binding inhibitor (BAMBI) can promote the production of ROS in the cytoplasm and mitochondria along with the DNA binding activity of C/ EBPβ, to ultimately promote adipocyte differentiation and adipogenesis (23). Collectively, these data suggest that mitochondria may play a role in BMP5-regulated cell proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunction resulting from the down-regulation of bone morphogenetic protein 5 may cause microtia

Qiu¹,

Zhang²,

Tang³

et al. 2021

Ann Transl Med

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Background: Bone morphogenetic protein 5 (BMP5) has been identified as one of the important risk factors for microtia; however, the link between them has yet to be clarified. In this study, we aimed to demonstrate the relationship of BMP5 with mitochondrial function and investigate the specific role of mitochondria in regulating microtia development.Methods: BMP5 expression was measured in auricular cartilage tissues from patients with and without microtia. The effects of BMP5 knockdown on cellular function and mitochondrial function were also analyzed in vitro. Changes in genome-wide expression profiles were measured in BMP5-knockdown cells.Finally, the specific impact of BMP5 down-regulation on mitochondrial fat oxidation was analyzed in vitro.Results: BMP5 expression was down-regulated in the auricular cartilage tissues of microtia patients.BMP5 down-regulation inhibited various cellular functions in vitro, including cell proliferation, mobility, and cytoactivity. The functional integrity of mitochondria was also damaged, accompanied by a decrease in mitochondrial membrane potential, reactive oxygen species (ROS) neutralization, and reduced adenosine triphosphate (ATP) production. Carnitine O-palmitoyltransferase 2 and diacylglycerol acyltransferase 2, two of the key regulators of mitochondrial lipid oxidation, were also found to be decreased by BMP5 downregulation.Conclusions: Down-regulation of BMP5 affects glycerolipid metabolism and fatty acid degradation, leading to mitochondrial dysfunction, reduced ATP production, and changes in cell function, and ultimately resulting in microtia. This research provides supporting evidence for an important role of BMP5 downregulation in affecting mitochondrial metabolism in cells, and sheds new light on the mechanisms underlying the pathogenesis of microtia.

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

Cited by 19 publications

References 38 publications

The Interplay Between Adipose Tissue and Vasculature: Role of Oxidative Stress in Obesity

The Interplay Between Adipose Tissue and Vasculature: Role of Oxidative Stress in Obesity

Bone morphogenetic protein signaling regulation of AMPK and PI3K in lung cancer cells and C. elegans

Mitochondrial dysfunction resulting from the down-regulation of bone morphogenetic protein 5 may cause microtia

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