Evaluating the effects of honey bee (Apis mellifera L.) venom on the expression of insulin sensitivity and inflammation-related genes in co-culture of adipocytes and macrophages

Abstract

Obese adipose tissue is characterized by adipocyte hypertrophy and a massive macrophage infiltration. The interaction between macrophages with mature adipocytes releases pro-inflammatory cytokines. This chronic inflammatory state can contribute to obesity-related complications, such as insulin resistance, type 2 diabetes and cardiovascular disease. Therefore, we can attempt to prevent and treat obesity-related diseases by inhibiting macrophage infiltration and blocking their interaction with adipocytes. Honey bee (Apis mellifera) venom (BV) has been reported to have anti-inflammatory effects. Although BV is used to treat chronic inflammatory diseases, few studies have addressed its use in obesity-associated inflammation. This study examines the inhibitory effects of BV on lipid accumulation in differentiating preadipocytes, inflammation, and insulin resistance in macrophages and adipocyte-macrophage co-culture system. We treated 3 T3-L1 preadipocytes with BV during differentiation. We later measured lipid accumulation and gene expression of master adipogenic transcription factors. After RAW264.7 and 3 T3-L1 cells were pretreated with BV, RAW264.7 cells were activated with LPS or co-cultured with pretreated 3 T3-L1 cells. Gene expression of pro-inflammatory cytokines and insulin sensitizing genes was measured in these cells. BV inhibited lipid accumulation and C/EBP alpha and PPAR gamma gene expression during intermediate and late 3 T3-L1 cell differentiation. BV also suppressed gene expression of pro-inflammatory cytokines (COX-2, iNOS, MCP-1, TNF-alpha, IL-1 beta and IL-6) in LPS-stimulated macrophages, and in co-culture of 3 T3-L1 adipocytes and RAW264.7 macrophages. However, adiponectin and GLUT-4 expression were both significantly increased by BV in co-culture. These findings demonstrate that BV attenuates adipocyte hypertrophy and improves obesity-related inflammation and insulin resistance in obese adipose tissue.