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Expression data from human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT)

ABSTRACT: The bone marrow (BM) is a major reservoir of resting memory T cells and long-lived plasma cells, capable of providing protection against recurrent infections. Whether the age-related accumulation of adipose tissue in the BM affects the functionality and maintenance of memory cells is not well understood. For the first time, we compare human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT) obtained from the same donors. Using microarrays, we show that fMAT significantly differs from tsWAT regarding specific gene expression profiles including inflammatory responses and adipogenesis. fMAT adipocytes express increased levels of pro-inflammatory molecules concomitant with an elevated generation of reactive oxygen species (ROS) and impaired function of plasma cells in the BM. The reduced expression of adipocyte-specific genes and a less mature adipocyte phenotype in fMAT, relative to tsWAT, suggests that fMAT has more immune regulatory functions. Our findings indicate that fMAT is a unique type of adipose tissue contributing to inflammation and impairment of plasma cell function. We used microarrays to detail the gene expression profil of fMat in comparison to tsWAT in regard to the inflammatory response, adipogenesis/fatty acid metabolism, and redox regulation, and identified distinct classes of up-regulated genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132411 | GEO | 2019/09/03

REPOSITORIES: GEO

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Project description:Abstract Background In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The individual ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to the development of inflammation and detrimental metabolic consequences. However, the molecular mechanisms underlying this fine-tuned regulation are far from being understood. Methods We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low responders (LowR HFD), showed a low susceptibility to the onset of adipose tissue inflammation, as opposed to their HFD counterpart. We identified the discriminants between LowR HFD and HFD vWAT samples and explored their function in Adipose Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. Results We quantified 6051 proteins. Among the candidates that most differentiate LowR HFD from HFD vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in LowR HFD, as compared to HFD. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was totally unknown, was another top-scored hit. SMYD3 expression was significantly higher in LowR HFD vWAT, as confirmed by western blot analysis. In vitro, we found that SMYD3 mRNA and protein levels decrease rapidly along the differentiation process of AD-hMSCs. Moreover, SMYD3 knock-down at the beginning of adipocyte differentiation resulted in reduced cell proliferation and, at longer term, reduced lipid accumulation in adipocytes. Conclusions Our study describes for the first time the role of SMYD3 as a regulator of adipocyte proliferation during the early steps of adipogenesis.

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Expression data from human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT)

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