Bone Morphogenetic Protein Signaling in Adipose Tissue Biology

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β superfamily, coordinate a spectrum of processes in adipose tissues, from lineage commitment of mesenchymal precursors to lipid metabolism and thermogenesis. In white adipose tissue, specific BMPs direct preadipocyte differentiation through SMAD-mediated transcriptional control of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs). In brown and beige depots, alternative BMP signals enhance mitochondrial biogenesis and uncoupling protein-1 expression, driving adaptive thermogenesis and energy expenditure. Beyond differentiation, BMP signalling modulates mature adipocyte functions: it influences insulin sensitivity by regulating GLUT4 levels, controls lipolytic rate via adrenergic receptor pathways, and shapes inflammatory crosstalk with resident macrophages. Dysregulation of BMP pathways has been implicated in obesity, insulin resistance and ectopic lipid accumulation, positioning these ligands, receptors and downstream SMAD effectors as attractive targets for metabolic intervention. Recent advances uncover how BMPs integrate extracellular cues with transcriptional networks to maintain adipose tissue plasticity, offering new avenues for the treatment of obesity and its comorbidities.

Research from Nature Portfolio

Recent studies have revealed that blockade of the TGFβ superfamily ligand GDF3 in obese mice enhances lipolytic activity, lowers β3-adrenergic receptor-mediated cAMP–PKA signalling, and improves glucose tolerance, suggesting a weight-independent strategy for metabolic health. Investigations using zebrafish and murine models have demonstrated that deletion of BMP8A leads to obesity via reduced AMPK and ACC phosphorylation, impaired fatty acid oxidation, and enhanced PPARγ-driven adipocyte differentiation, implicating BMP8A in cross-talk between immune regulation and adipogenic pathways. Foundational work has further described BMP2 and BMP6 as potent insulin sensitizers in mature adipocytes by upregulating PPARγ and GLUT4, thereby enhancing insulin-stimulated glucose uptake and modulating gene networks governing glucose and lipid homeostasis.

Bone Morphogenetic Protein Signaling in Adipose Tissue Biology publication trend

The graph below shows the total number of articles in bone morphogenetic protein signaling in adipose tissue biology across all publications each year (not limited to Nature Index journals).

Technical terms

Bone morphogenetic proteins (BMPs): Growth factors of the TGFβ superfamily that regulate development, cell differentiation and tissue homeostasis.

Adipogenesis: The process by which preadipocytes differentiate into lipid-laden mature adipocytes under transcriptional control of PPARγ and C/EBPs.

SMAD proteins: Intracellular effectors that transduce signals from TGFβ family receptors to the nucleus to regulate gene expression.

PPARγ (Peroxisome proliferator-activated receptor gamma): A nuclear receptor essential for adipocyte differentiation and lipid metabolism.

ALK7 (Activin receptor-like kinase 7): A type I receptor of the TGFβ superfamily preferentially expressed in adipose tissue, modulating lipolysis and insulin sensitivity.

Lipolysis: The enzymatic breakdown of stored triglycerides in adipocytes into free fatty acids and glycerol, often regulated by adrenergic signalling.

Thermogenesis: Heat production by brown or beige adipocytes, mediated by mitochondrial uncoupling proteins to expend energy and regulate body temperature.

Beige adipocytes: Thermogenically competent cells within white adipose depots that can be induced to express brown-fat-like characteristics under certain stimuli.

References

1. Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3. Nature Communications (2025).
2. Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation. Communications Biology (2023).
3. BMPs as new insulin sensitizers: enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation. Scientific Reports (2017).
4. Targeting activin receptor-like kinase 7 ameliorates adiposity and associated metabolic disorders. JCI Insight (2023).
5. Human ACVR1C missense variants that correlate with altered body fat distribution produce metabolic alterations of graded severity in knock-in mutant mice. Molecular Metabolism (2024).
6. Bone Morphogenetic Protein 2 Enhances Porcine Beige Adipogenesis via AKT/mTOR and MAPK Signaling Pathways. International Journal of Molecular Sciences (2024).
7. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality. PLOS ONE (2013).
8. TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment. Stem Cell Research & Therapy (2020).
9. Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity. eLife (2014).