Lipid, inflammatory and intestinal microbiota profile of mice fed a high-fat diet submitted to supplementation with different doses of curcumin

Abstract

Obesity and its comorbidities have become epidemic worldwide. Insulin resistance, dyslipidemia, hepatic steatosis are the extensively researched and reported reactions. Associated with the increase in the prevalence of Obesity has been expanding the search for drugs or substances that can prevent and/or treat these diseases, substances used by the lay public without dose control and time of use. A study developed by our research group showed that supplementation of turmeric extract led to the development of possible pancreatic steatosis in the supplemented groups, regardless of the diet ingested. At the same time, it is known that the Intestinal Microbiota (IM) has a strong relationship with metabolic disorders associated with Obesity, besides having a role in the onset of pancreatic inflammation and a possible damage in this area. It could also increase the permeability of the intestine, promoting translocation of the MI to the pancreas, causing secondary infections.Thus, the hypothesis of this project is that the supplementation of different doses of curcumin could lead to different effects on the intestinal microbiota and pro-inflammatory and cytokine profile, as well as possible pancreatic and hepatic alterations. Fifty male C57BL/6 mice, 30 days after birth, split into 5 groups: 1. Standard diet (SD, n = 10); 2. High-fat diet (DH + n = 10); 3. High-fat diet and curcumin extract (DH + C50, n = 10); 4. High-fat diet and curcumin extract (DH + C250, n = 10); 5. High-fat diet and curcumin extract (DH + C500, n = 10). All under controlled lighting and temperature conditions. The animals in group 1 will be fed a standard control diet (AIN 93 G), the animals in group 2 will be fed a purified high-fat diet (AIN 93 HF 60%) and both will receive by gavage only the vehicle (carboxymethylcellulose - CMC 1%). The animals in the treated groups (3, 4 and 5) will be fed a purified high-fat diet (AIN 93 HF 60%) added by curcumin by gavage at different dosages (50, 250 and 500mg/kg diluted in 1% CMC) for 12 weeks. All groups will receive food and water ad libitum. Serum lipids, glycemia, insulin, intestinal microbiota, tissue weight: hepatic, brown adipose, epididymal adipose, retroperitoneal adipose, pancreas, intestine and liver will be evaluated. The gene expression of inflammatory cytokines in the hepatic and white adipose tissue will be evaluated by real-time PCR. In addition, histological analysis of the pancreas, liver and intestine will be performed. All the procedures to be carried out in this research were approved by the Ethics Committee for research on animals of this institution (Protocol No. 089/2017). (AU)