Effect Of Chlorogenic Acid On Chronic Inflammation In High-fat Diet-induced Obese Rat Adipose Tissue

Long-term exposure to a high-carbohydrate, high-fat diet can lead to a systemic disorder of lipid metabolism, resulting in obesity. Obesity maintains a low-degree inflammatory state and results in insulin-resistance and type 2 diabetes. Chlorogenic acid (CGA) is a polyphenolic compound with many isomers and derivatives. Previous research has indicated that CGA had a good effect in antioxidant, anti-inflammation and lowering blood-glucose. However, the related research is rarely reported on the effect of CGA on obesity-relative inflammatory and lipid metabolism. This study aimed to evaluate the anti-inflammatory effect of CGA in high-fat diet-induced obese rats.Forty male Sprague-Dawley (SD) rats, weighing 219.37±2.01 g, were chosen as experimental materials. After a week of acclimatization, the rats were randomly assigned to four groups (n=10):the normal control (NC) group, high-fat diet (HFD) group, HFD with low-dose CGA (20 mg/kg; HFD-LC) group, and HFD with high-dose CGA (90 mg/kg; HFD-HC) group. For 12 weeks, the HFD-LC and HFD-HC groups were orally administered CGA by gavage needle once a day, while the NC and HFD groups received carrier solution (sterile saline). NC rats were fed a normal chow diet, while all other groups were fed the HFD diet. At the end of the 12th week, the animals were killed by exsanguination from the ophthalmic artery. Serum interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-a), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) levels were determined. Expression of genes related to TG metabolism, macrophage biomarkers, and inflammation was assessed by real-time PCR. Protein expression of NF-κB, PPARy2, and phosphorylated IκBα was evaluated by western blotting, and the histology of adipose tissue examined.After feeding for 12 weeks, the HFD group showed a increase in 1) the final body weight, body weight gain, and visceral adipose tissue weight,2) the serum TC, TG, FFA, IL-6, MCP-1, and TNF-a concentrations,3) the mRNA level of inflammatory factor, marker of Ml macrophages, key enzyme genes involved in TG synthesis and a decrease in the expression of M2 macrophages marker, Pnpla2 and Pparg2. The protein expression of PPARy2 and NF-κB p65, IκBα protein phosphorylation were similar to those related to mRNA expression. However, supplementation of CGA in the high-fat diet for rats ameliorated the development of obesity, macrophage infiltration, and steatosis. In addition, CGA decreased the expression of NF-κB and its downstream inflammatory cytokines, but increased the expression of PPARγ2, in a dose-dependent manner.In conclusion, supplementation of a high-fat diet with CGA may retard weight gain; furthermore, it reduces macrophage infiltration and inactivates the inflammatory signaling pathway. The protective effect of CGA may be due to its inhibition of the NF-κB signaling pathway, macrophage infiltration, TG synthesis, and the up-regulation of PPARγ2 and TG degradation in adipose tissue.