十字花科蔬菜衍生物indole-3-carbinol對高脂飲食誘導肥胖相關疾病調節及其機制之探討

Abstract

The objective of this study was to investigate the effects of indole-3-carbinol (I3C), a compound derivated from cruciferous vegetables, on diet-induced obesity and its associated pathological conditions. The first study was to examine the effects of I3C on obesity and its related factors in high fat diet-induced obese (DIO) mice. Secondly, the effects of I3C on high-fat diet induced hepatic steatosis and on lipid metabolism associated genes were studied. Finally, the model of co-culture of adipocytes and macrophages was conducted to evaluate the anti-obesity activity mechanisms of I3C. For the first two studies, C57BL/6 mice were randomly divided into three groups, and received basal diet, high fat diet (HF), as well as high fat diet + 5 mg I3C/kg intraperitoneally (HFI) 3 times per week for 12 weeks. Results showed that body weight and epididymal adipose tissue weight were greater, and adipocytes were larger in the HF group than in the basal and HFI groups. Compared with the HF group, the HFI group had improved glucose tolerance, a higher serum adiponectin concentration, and lower serum glucose, triglyceride, insulin, and leptin concentrations, as well as less F4/80 expression in epididymal adipose tissue (p<0.001). Furthermore, I3C treatment decreased acetyl CoA carboxylase (ACC) mRNA expression (p<0.05) and increased peroxisome proliferators–activated receptor-γ (PPARγ) protein expression (p<0.05) in epididymal adipose tissue of DIO mice. In the second study, mice fed with high-fat diet had upregulation on serum lipid profiles and on hepatic TG accumulation. I3C reduced high fat diet-induced hepatic steatosis, glucose intolerance, lowered serum glucose, serum and hepatic triglyceride levels, and decreased expressions of sterol response element binding protein-1 (SREBP-1) and ACC mRNA, increased PPARα mRNA expressions in liver comparing to those of HF mice. However, no significant difference was observed in serum and fecal cholesterol levels between HFI and HF groups. As in macrophage and primary adipocyte co-culture study, I3C treatment decreased expression of inducible nitric oxide synthase (iNOS), lowered nitrite and interleukin-6 (IL-6) concentrations in medium, and enhanced mRNA expression of PPAR-γ. I3C also inhibited intracellular lipid accumulation in hypertrophic adipocytes, indicating an inhibition of adipocyte differentiation. In conclusion, I3C possesses anti-obesity activity as observed from decreased adiposity and infiltrated macrophages in epididymal adipose tissue of DIO mice. These reductions were associated with improved glucose tolerance and with modulated expression of adipokines and hepatic lipogenic-associated gene products. Besides, the possible mechanisms for anti-obesity effects of I3C may be involved in inhibition of macrophage-induced inflammatory changes and modulation expression of PPAR-γ and hepatic lipogenic genes.