Curcumin Reduces Hepatic and White Adipose Tissue Inflammation and Expression of Specific Zinc Transporters in Diet-Induced Obese Mice

Abstract

Abstract Objectives Obesity is a complex metabolic disease, that is often associated with non-alcoholic fatty liver disease (NAFLD). Inflammation is a common feature of both diseases. Curcumin, a traditionally used spice in Asia, exerts anti-inflammatory effects in liver and white adipose tissue (WAT) of diet-induced obese (DIO) mice. However, mechanisms involved in these beneficial effects remain obscure. Zinc is an important micronutrient involved in inflammatory responses. Whole-body zinc homeostasis plays a critical role in decreasing tissue specific inflammation. Zinc homeostasis is maintained mainly by zinc transporters known as ZnT (zinc transporters) and Zip (Zrt and Irt-like proteins) family. We propose that zinc transporters may contribute to curcumin's protective metabolic effects. Thus, the objective of this research was to determine curcumin's effects on inflammatory markers and zinc transporters in liver and WAT from DIO mice. Methods Male B6 mice were fed a HFD (45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for fourteen weeks. Serum triglycerides (TG) and free fatty acid (FFA) levels were measured. mRNA levels for inflammatory markers and zinc transporters were determined in WAT and liver by qRT-PCR. Results No significant changes were observed in body weight, serum TG and FFA levels with curcumin supplementation. However, gene expression of inflammatory markers, including Stat1, and Nf-KB subunit p65 were significantly reduced in liver and WAT from HFC group compared to HF (P < 0.05). Furthermore, curcumin reduced hepatic zinc transporters Zip10, Zip14, ZnT10 but increased ZnT9 expression. In WAT, curcumin significantly reduced mRNA levels for Zip1, Zip14, ZnT1, and ZnT7 (P < 0.05). Conclusions Our results indicate that zinc transporters may in part mediate the anti-inflammatory properties of curcumin, particularly Zip14, in WAT and liver of DIO mice. Future mechanistic studies are necessary to establish whether zinc transporters are required for curcumin's anti-inflammatory effects in obesity and associated NAFLD. Funding Sources AHA grant# 19AIREA34450279.