Abstract
The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. Recently, microRNAs (miRNAs) were identified as important regulators of WAT functions. Herein, we cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with macrophage-conditioned medium (MacCM) and performed an Affimetrix miRNA array to identify miRNAs differentially expressed under inflammatory conditions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species. In subcutaneous WAT, miR-146a was elevated in both human and murine obesity. Transfection of miR-146a mimics prevented the MacCM-induced inflammatory response in SGBS adipocytes as seen by reduced levels of IL-8 and MCP-1 mRNA and protein. We identified IRAK1 and TRAF6 as targets of miR-146a in human adipocytes and detected a reduced inflammation-induced activation of JNK and p38 upon miR-146a transfection. Taken together, we could show that miR-146a reduces the inflammatory response in human adipocytes. In a negative feedback loop miR-146a might contribute to the regulation of inflammatory processes in WAT and possibly prevent an overwhelming inflammatory response.
Highlights
The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis
Simpson-Golabi-Behmel syndrome (SGBS) adipocytes on day 14 of adipogenic differentiation were treated with 10% macrophage-conditioned medium (MacCM) or the corresponding vehicle control
This inflammatory state alters adipocyte function and is positively correlated with a decreased metabolic control promoting obesity-related diseases such as type 2 diabetes mellitus31. miRNAs are modulators of the immune response and especially miR-146a is known to be a fine tuner of the inflammatory response, which possibly prevents uncontrolled inflammation[32]
Summary
The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. MicroRNAs (miRNAs) were identified as important regulators of WAT functions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species. Transfection of miR-146a mimics prevented the MacCM-induced inflammatory response in SGBS adipocytes as seen by reduced levels of IL-8 and MCP-1 mRNA and protein. Several studies in the last years revealed that white adipose tissue (WAT) is not a simple energy storage organ, but influences the whole organism by the secretion of adipokines, which are involved in important functions including metabolism, energy homeostasis and inflammation[1]. MiRNAs are a class of small, non-coding RNA molecules, only 18–25 nucleotides in length[9] They play an important role in the regulation of cellular gene expression by either suppressing translation of protein coding genes or by cleaving target mRNA to induce their degradation[8,9]. A clinical study recently reported a significant reduction of miR-146a and increased pro-inflammatory IL-8 in serum of type 2 diabetes patients compared to a non-diabetic control group[22]
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