Oral Angiotensin-(1–7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet

AbstractObesity is characterized by a pro-inflammatory state commonly associated with type 2 diabetes and fat-liver disease. In the last few years, different studies pointed out the role of Angiotensin (Ang)-(1–7) in the metabolic regulation. The aim of the present study was to evaluate the effect of oral-administration of Ang-(1–7) in metabolism and inflammatory state of high-fat feed rats. Twenty-four male Sprague Dawley rats were randomized into three groups: High Fat Diet (HFD); Standard Diet (ST); High Fat Diet+Angiotensin-(1–7) [HFD+Ang-(1–7)]. Glycemic profile was evaluated by glucose tolerance and insulin sensitivity tests, plasmatic glucose and insulin. Cholesterol, HDL and triglycerides analyses presented lipidic profile. RT-PCR evaluated mRNA expression to ACE, ACE2, resistin, TLR4, IL-6, TNF-α and NF-κB genes. The main results showed that oral Ang-(1–7) decreased body weight and abdominal fat-mass. In addition, HFD+Ang-(1–7) treated rats presented enhanced glucose tolerance, insulin-sensitivity and decreased plasma-insulin levels, as well as a significant decrease in circulating lipid levels. These alterations were accompanied by a marked decreased expression of resistin, TLR4, ACE and increased ACE2 expression in liver. Furthermore, Ang-(1–7) decreases phosphorylation of MAPK and increases NF-κB expression. These alterations diminished expression of interleukin-6 and TNF-α, ameliorate inflammatory state in liver. In summary, the present study showed that oral-treatment with Ang-(1–7) in high-fat feed rats improved metabolism down-regulating resistin/TLR4/NF-κB-pathway

Proteomic White Adipose Tissue Analysis of Obese Mice Fed with a High-Fat Diet and Treated with Oral Angiotensin-(1-7)

AbstractAngiotensin-(1–7) has been described as a new potential therapeutic tool for the treatment and prevention of metabolic disorders by regulating several pathways in visceral white adipose tissue (vWAT). The aim of this study was to access the proteins differentially regulated by Ang-(1–7) using proteomic analysis of visceral adipose tissue. Male mice were divided into three groups and fed for 60 days, with each group receiving one of the following diets: standard diet+HPβCD (ST), high fat diet+HPβCD (HFD) and high fat diet+Ang-(1–7)/HPβCD (HFD+Ang-(1–7)). Body weight, fat weight and food intake were measured. At the end of treatment, Ang-(1–7) induced a decrease in body and fat weight. Differential proteomic analysis using two-dimensional electrophoresis (2-DE) combined with mass spectrometry were performed. Results of protein mapping of mesenteric adipose tissue using 2-DE revealed the presence of about 450 spots in each gel (n=3/treatment) with great reproducibility (>70%). Image analysis and further statistical analysis allowed the detection and identification of eight proteins whose expression was modulated in response to HFD when compared to ST. Among these, two proteins showed a sensitive response to Ang-(1–7) treatment (eno1 and aldehyde dehydrogenase). In addition, three proteins were expressed statistically different between HFD+Ang-(1–7) and HFD groups, and four proteins were modulated compared to standard diet. In conclusion, comparative proteomic analysis of a mice model of diet-induced obesity allowed us to outline possible pathways involved in the response to Ang-(1–7), suggesting that Ang-(1–7) may be a useful tool for the treatment of metabolic disorders