Gallic acid regulates adipocyte hypertrophy and suppresses inflammatory gene expression induced by the paracrine interaction between adipocytes and macrophages in vitro and in vivo.

Abstract

Obesity-induced chronic inflammation in adipose tissue plays a critical role in the development of insulin resistance and various lifestyle-related diseases. Although gallic acid (GA) is known to exert protective effects on obesity-related complications, its function in adipose tissue inflammation has not been elucidated. Recently, we reported that GA exerts protective effects against inflammation. To test our hypothesis that the anti-inflammatory effect of GA partially contributes to the improvement of metabolic diseases, we examined the effect of GA on inflammation caused by adipocyte-macrophage crosstalk in obesity. We showed that GA enhanced adipocyte differentiation in 3 T3-L1 adipocytes. Consistent with the enhancement of adipogenesis, GA decreased the gene expression of monocyte chemoattractant protein-1 and increased that of adiponectin and the upstream mediator peroxisome proliferator-activated receptor gamma. GA also reduced inflammatory mediator expression induced by the co-culture of 3 T3-L1 adipocytes with RAW 264 macrophages. Diet-induced obese mice treated with GA showed decreased serum cholesterol levels and adipocyte size, and improved insulin sensitivity without changes in body weight. Moreover, GA-treated mice had decreased expression of interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, F4/80, and sterol regulatory element binding transcription factor-1 in their adipose tissue. These results indicate that GA suppresses adipocyte hypertrophy and inflammation caused by the interaction between adipocytes and macrophages, thereby improving metabolic disorders such as insulin resistance and dyslipidemia.