Expression of the Bone Morphogenetic Protein Receptor 1A Gene (BMPR1A) in Adipose Tissue and BMPR1A Genetic Variation are Associated with Human Obesity

Böttcher, Yvonne; Schleinitz, Dorit; Unbehauen, Hanne; Klöting, Nora; Ruschke, Karen; Enigk, Beate; Tönjes, Anke; Wolf, Samuel; Tseng, YH; Blüher, Matthias; Stumvoll, M; Kovács, Péter

doi:10.1055/s-2008-1076221

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most BMP signaling is mediated via two receptors: type 1 (BMPR1) and/or type 2 (BMPR2) and downstream activation of the SMAD transcription factors (593,710). Interestingly, specific genotypes of the BMPR isoforms BMPR1A and BMPR2 have been shown to associate with obesity in human (87,134,800). Of note, specific deletion of BMPR1a in Myf5-expressing cells (precursors of classic brown adipocytes) results in a severe paucity of BAT and the compensatory activation of WAT browning (805).…”

Section: U N C O R R E C T E D P R O O F Smentioning

confidence: 99%

Adipose Organ Development and Remodeling

Cinti

2018

Comprehensive Physiology

142

121

View full text Add to dashboard Cite

During the last decades, research on adipose tissues has spread in parallel with the extension of obesity. Several observations converged on the idea that adipose tissues are organized in a large organ with endocrine and plastic properties. Two parenchymal components: white (WATs) and brown adipose tissues (BATs) are contained in subcutaneous and visceral compartments. Although both have endocrine properties, their function differs: WAT store lipids to allow intervals between meals, BAT burns lipids for thermogenesis. In spite of these opposite functions, they share the ability for reciprocal reversible transdifferentiation to tackle special physiologic needs. Thus, chronic need for thermogenesis induces browning and chronic positive energy balance induce whitening. Lineage tracing and data from explant studies strongly suggest other remodeling properties of this organ. During pregnancy and lactation breast WAT transdifferentiates into milk-secreting glands, composed by cells with abundant cytoplasmic lipids (pink adipocytes) and in the postlactation period pink adipocytes transdifferentiate back into WAT and BAT. The plastic properties of mature adipocytes are supported also by a liposecretion process in vitro where adult cell in culture transdifferentiate to differentiated fibroblast-like elements able to give rise to different phenotypes (rainbow adipocytes). In addition, the inflammasome system is activated in stressed adipocytes from obese adipose tissue. These adipocytes die and debris are reabsorbed by macrophages inducing a chronic low-grade inflammation, potentially contributing to insulin resistance and T2 diabetes. Thus, the plastic properties of this organ could open new therapeutic perspectives in the obesity-related metabolic disease and in breast pathologies. © 2018 American Physiological Society. Compr Physiol 8:1357-1431, 2018.

show abstract

Section: U N C O R R E C T E D P R O O F Smentioning

confidence: 99%

Adipose Organ Development and Remodeling

Cinti

2018

Comprehensive Physiology

142

121

View full text Add to dashboard Cite

show abstract

“…Bone Morphogenetic Proteins (BMPs) are members of the TGF-β family of growth and differentiation factors and are known to play central roles in pancreas and islet development (13,14). Moreover, emerging data points to BMPs, particularly BMP-2 and − 4, as in ammatory factors, which are also associated with obesity, T2D and beta cell dysfunction (15)(16)(17)(18)(19). mRNA expression of BMP-2 and − 4 is upregulated in pancreatic islets of db/db mice, and BMP-2 expression is induced by pro-in ammatory cytokines in rodent and human islets in vitro (18,20,21).…”

Section: Introductionmentioning

confidence: 99%

Beta cell dysfunction and dedifferentiation induced by Bone Morphogenetic Protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding

Urizar¹,

Prause

Ingerslev

et al. 2022

Preprint

View full text Add to dashboard Cite

Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from individuals with diabetes and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1 and Hey-1 which are transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism by which BMP-2 induces beta cell dysfunction and loss of cell maturity. Mouse islets exposed to BMP-2 for 10 days showed impaired glucose-stimulated insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of cell maturity and proliferation markers specific to the beta cell such as Ins1, Ucn3 and Ki67 and increased expression of Id1-4, Hes-1 and Hey-1. Top 30 most regulated proteins significantly correlated with corresponding mRNA expression. BMP-2-induced gene expression changes were associated with a predominant reduction in acetylation of H3K27 and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2 induces loss of beta cell maturity and suggest that remodeling of H3K27ac and decreased NeuroD1 DNA binding activity participate in the effect of BMP-2 on beta-cell dysfunction.

show abstract

Expression of the Bone Morphogenetic Protein Receptor 1A Gene (BMPR1A) in Adipose Tissue and BMPR1A Genetic Variation are Associated with Human Obesity

Cited by 2 publications

References 0 publications

Adipose Organ Development and Remodeling

Adipose Organ Development and Remodeling

Beta cell dysfunction and dedifferentiation induced by Bone Morphogenetic Protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding

Contact Info

Product

Resources

About