B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammation

B cell activation factor (BAFF) is a novel member of the TNF ligand superfamily, mainly produced by myeloid cells. BAFF has been shown to participate in B-cell survival and B- and T-cell maturation. BAFF expression in adipocytes has been recently demonstrated. In the current study, we verified that BAFF expression is increased during adipocyte differentiation. BAFF expression was augmented by TNF-alpha treatment and was decreased by rosiglitazone treatment. BAFF secretion in lean and in ob/ob mice sera were compared and smaller amount of BAFF was secreted in ob/ob mice. mRNA and protein expression were different between epididymal and visceral adipose tissue. BAFF expression was also increased in ob/ob mouse adipose tissue. We sought to identify known BAFF receptors (BAFF-R, BCMA, and TACI) in adipocytes, and determined that all three were present and upregulated during adipocyte differentiation. However, the expression of TACI was distinct from that of BAFF-R and BCMA under TNF-alpha and BAFF ligand treatment. BAFF-R and BCMA expression levels were upregulated under pro-inflammatory conditions, but TACI was reduced. Conversely, BAFF-R and BCMA expression levels were downregulated by rosiglitazone treatment, but TACI was increased. Taken together, our results suggest that BAFF may be a new adipokine, representing a link between obesity and inflammation.

The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling

In our previous study, we have shown that berberine has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect is due to the down-regulation of adipogenic enzymes and transcription factors. Here we focused more on anti-inflammatory effect of berberine using real time RT-PCR and found it changes expressions of adipokines. We hypothesized that anti-adipogenicity of berberine mediates anti-inflammtory effect and explored leptin as a candidate mediator of this signaling. We studied this hypothesis by western blot analysis, but our results showed that berberine has no effect on the phosphorylations of STAT-3 and ERK which have important roles on leptin signaling. These results led us to conclude that the anti-inflammatory effect of berberine is not mediated by the inhibition of leptin signal transduction. Moreover, we have found that berberine down-regulates NF-kappaB signaling, one of the inflammation-related signaling pathway, through western blot analysis. Taken together, the anti-inflammatory effect of berberine is not mediated by leptin, and berberine induces anti-inflammatory effect independent of leptin signaling.

The Interaction of Adipose Tissue with Immune System and Related Inflammatory Molecules

BACKGROUND: Adipose tissues were initially introduced as energy storages, but recently they have become famous as an endocrine organ which produces and secretes various kinds of molecules to make physiologic and metabolic changes in human body. It has been studied that these molecules are secreted in abundance as the adipose tissue becomes bigger along with obesity. Furthermore, it has been found that they are mediating systemic inflammation and generation of metabolic diseases such as type 2 diabetes and atherosclerosis. On the basis of these, we studied previous papers which have been researched about the interaction between preadipocytes and macrophages, adipose tissues and lymph nodes, and adipose tissue secreting molecules. RESULTS: Firstly, preadipocytes and macrophages are expressing similar transcriptomes and proteins, and preadipocytes can be converted to mature macrophages which have phagocytic activity. Moreover, the monocytes, which initially located in the bone marrow, are filtrated to the adipose tissue by monocyte chemotatic protein-1 and are matured to macrophages by colony stimulating factor-1. Secondly, adipose tissues and their associated lymph nodes are interacting each other in terms of energy efficiency. Lymph nodes promote lipolysis in adipose tissues, and polyunsaturated fatty acids in adipocytes become energy sources for dendritic cells. Lastly, adipose tissues produce and secrete proinflammatory molecules such as leptin, adiponectin, TNF-alpha, IL-6, and acute phase proteins, which induce the inflammation and potentially generate metabolic diseases. CONCLUSION: According to these, we can link adipose tissues to inflammation, but we need to affirm the actual levels and roles of adipose tissue-derived proinflammatory molecules in human body.

Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte

Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-alpha, IL-6, C- reactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors.

Inflammatory Gene Expression Patterns Revealed by DNA Microarray Analysis in TNF-alpha-treated SGBS Human Adipocytes

We report here the use of human inflammation arrays to study the inflammatory gene expression profile of TNF-alpha- treated human SGBS adipocytes. Human preadipocytes (SGBS) were induced to differentiate in primary culture, and adipocyte differentiation was confirmed, using Oil Red O staining. We treated the differentiated adipocytes with TNF-alpha, and RNA from differentiated adipocytes with or without TNF-alpha treatment was hybridized to MWG human inflammation arrays to compare expression profiles. Eleven genes were up- or down-regulated in TNF-alpha-treated adipocytes. As revealed by array analysis, among 6 up-regulated genes, only eotaxin-1, monocyte chemoattractant protein-1 (MCP-1), and vascular cell adhesion molecule 1 isoform a precursor (VCAM1) were confirmed by real-time polymerase chain reaction (PCR). Similarly, among 5 down-regulated genes, only IL-1 family member 5 (IL1F5), a disintegrin and metalloprotease with thrombospondin motifs-1 preproprotein (ADAMTS1), fibronectin 1 isoform 1 preprotein (FN1), and matrix metalloproteinase 15 preprotein (MMP15) were confirmed by real-time PCR. There was a substantial increase (50-fold) in eotaxin-1 in response to TNF-alpha. Taken together, we have identified several inflammatory molecules expressed in SGBS adipocytes and discovered molecular factors explaining the relationship between obesity and atherosclerosis, focusing on inflammatory cytokines expressed in the TNF-alpha-treated SGBS cells. Further investigation into the role of these up- or down-regulated cytokine genes during the pathological processes leading to the development of atherosclerosis is warranted.