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/EBPα and PPARγ 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‐α, IL‐1β 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.

Honey and its nutritional and anti-inflammatory value

“… Honey bee ( Apis mellifera ) venom inhibited lipid accumulation and C/EBPα and PPARγ gene expression during intermediate and late 3 T3-L1 cell differentiation. It also suppressed gene expression of pro-inflammatory cytokines (COX-2, iNOS, MCP-1, TNF-α, IL-1β and IL-6) in LPS-stimulated macrophages, and in co-culture of 3 T3-L1 adipocytes and RAW264.7 macrophages [ 99 ]. Honeys produced from Echium plantagineum L decrease NO levels in lipopolysaccharide-stimulated murine macrophage-like cells (RAW 264.7) up to 40% at concentrations of 0.25 mg/mL [ 100 ].…”

Pharmacological effects and mechanisms of bee venom and its main components: Recent progress and perspective

“…Besides, bvPLA 2 also attenuated HFD-induced obesity in mice ( Jeong et al, 2021 ). In addition, BV could attenuate adipocyte hypertrophy, as well as improve insulin resistance and obesity-related inflammation in obese adipose tissue ( Kim H. Y. et al, 2020 ). The above results are shown in Table 7 .…”

Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes

“…However, gene expression studies demonstrate ability of bee venom to inhibit lipid accumulation and downregulate adipogenic transcription factors, such as PARγ and C/EBPα. 172 Furthermore, bee venom was recently shown to improve GLUT-4 expression and insulin sensitivity suggesting bee venom as a potential treatment for chronic inflammation in obesity as well as diabetes. 172 Indeed, venom from the Egyptian honeybee Apis mellifera lamarckii , improved diabetic status in alloxan treated rats.…”

“… 172 Furthermore, bee venom was recently shown to improve GLUT-4 expression and insulin sensitivity suggesting bee venom as a potential treatment for chronic inflammation in obesity as well as diabetes. 172 Indeed, venom from the Egyptian honeybee Apis mellifera lamarckii , improved diabetic status in alloxan treated rats. 173 Beneficial effects were believed to be related to the melittin and phospholipase A 2 components of the venom.…”