Expression of adrenomedullin in adipose tissue of lean and obese women

Abstract

Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions. Methods: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR. Results: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor a mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome. Conclusion: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.

The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

“…2d-f). By contrast, we detected adrenomedullin, as already reported [25], in nonfat-filled cells (Fig. 2d-f).…”

Response to Comment on: Harmancey et al. (2007) Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin: Diabetes 56:553–563

“…We believe that the development of insulin resistance during obesity may lead to an effective increase in adrenomedullin plasma concentration because the peptide would no longer be negatively controlled by insulin. This hypothesis is supported by recent results, demonstrating a positive correlation of adrenomedullin levels in omental adipose tissue with BMI and homeostasis model assessment index in obese patients with no endocrine, cardiovascular, hepatic, renal, or inflammatory disease (10).…”

Role of adrenomedullin system in lipid metabolism and its signaling mechanism in cultured adipocytes

“…Li et al (14) studied the expression of AM and resistin in 3T3-L1 preadipocytes and adipocytes by Northern blot analysis and showed that AM mRNA was expressed in 3T3-L1 preadipocytes but was undetectable in adipocytes, whereas resistin mRNA was not detected in 3T3-L1 preadipocytes but was expressed in adipocytes. It was also reported that preadipocytes at early differentiation stages secreted AM, but mature adipocytes did not secrete AM (34). In contrast, a recent study showed that the expression of AM mRNA increased in human mesenchymal stem cell-derived adipocytes at days 4,8,12, and 18 (16).…”

“…In addition, studies in humans showed that plasma AM correlates with body mass index, and circulating AM is elevated in overweight patients with essential hypertension (34) and is decreased with a reduction of body weight by a hypocaloric diet (18), suggesting a role of AM in human adipose tissue.…”