Background Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans. Objective To characterise BMP2 expression, BMP2-SMAD1/5/8 signalling, and BMP2’s potential effect on proliferation and adipogenesis in human subcutaneous abdominal and gluteal AT and its constituent preadipocytes. Methods BMP2 expression was measured in whole AT and immortalised preadipocytes via qPCR and Western blot; secreted/circulating BMP2 was measured by ELISA. The effect of BMP2 on preadipocyte proliferation was evaluated using a fluorescent assay. BMP2’s effect on adipogenesis in immortalised preadipocytes was determined via qPCR of adipogenic markers and cellular triacylglycerol (TAG) accumulation. BMP2-SMAD1/5/8 signalling was assessed in immortalised preadipocytes via Western blot and qPCR of ID1 expression. Results BMP2 was expressed and released by abdominal and gluteal AT and preadipocytes. Exogenous BMP2 dose-dependently promoted adipogenesis in abdominal preadipocytes only; 50ng/ml BMP2 increased PPARG2 expression (10-fold compared to vehicle, p<0.001) and TAG accumulation (3-fold compared to vehicle; p<0.001). BMP2 stimulated SMAD1/5/8 phosphorylation and ID1 expression in abdominal and gluteal preadipocytes but this was blocked by 500nM K02288, a type 1 BMP receptor inhibitor (p<0.001). Co-administration of 500nM K02288 also inhibited the pro-adipogenic effect of 50ng/ml BMP2 in abdominal cells; >90% inhibition of TAG accumulation (p<0.001) and ~50% inhibition of PPARG2 expression (p<0.001). The endogenous iron regulator erythroferrone reduced BMP2-SMAD1/5/8 signalling by ~30% specifically in subcutaneous abdominal preadipocytes (p<0.01), suggesting it plays a role in restricting the expansion of the body’s largest AT depot during energy deficiency. Additionally, a waist-hip ratio-increasing common polymorphism near BMP2 is an eQTL associated with ~15% lower BMP2 expression in abdominal and gluteal AT (p<0.05) as well as altered adipocyte size in male abdominal AT (p<0.05). Conclusions These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.
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Case series Patients: Male, 25-year-old • Male, 29-year-old • Female, 39-year-old • Male, 32-year-old Final Diagnosis: Folliculitis Symptoms: Rash Medication: — Clinical Procedure: Sleeve gastrectomy Specialty: Dermatology • Surgery Objective: Unusual clinical course Background: Obesity is one of the leading causes of preventable death worldwide. Due to its increasing incidence and the difficulty in reducing its morbidity and mortality using nonsurgical methods, the demand for bariatric surgery has risen in recent times. Sleeve gastrectomy is one of the most common types of bariatric surgery, and like any other surgery, it carries a series of risks. Case Reports: Although complications such as gastrointestinal leaks are widely reported, there is limited literature available on cutaneous complications. Here, we report 4 cases of patients showing a peculiar skin rash 2–4 weeks following sleeve gastrectomy. We also discuss some of the mechanisms that may underlie this correlation. Conclusions: There is a need for further epidemiological studies to determine the prevalence of this rash. Further studies are also needed to determine the exact etiology of this rash.
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