High fat diet aggravates cardiomyopathy in murine chronic Chagas disease

Abstract

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection - the indeterminate and chronic stages - has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology.

Diet Alters Serum Metabolomic Profiling in the Mouse Model of Chronic Chagas Cardiomyopathy

“…A global metabolomic analysis of mice was used to assess the effect of diets on the pathogenesis of chronic Chagas cardiomyopathy and host metabolism. T. cruzi infection and maintenance of infected mice have been previously described [14,16]. In brief, male 6-8 weeks CD1 mice (purchased from Jackson Laboratory) were infected intraperitoneally (i.p.)…”

“…Although RD diet was designed to be used as a control diet, it is also considered a carbohydrate-rich diet (RD; 70% carbohydrate calories (20% calories of protein and 10% calories of fat)) when compared to the "standard" rodent diet PicoLab #5058. [14,16]. Uninfected mice were fed on either HFD (n = 20) or RD (n = 20) and used as respective controls in all the experiments.…”

“…Uninfected mice were fed on either HFD (n = 20) or RD (n = 20) and used as respective controls in all the experiments. Mice were euthanized and livers were harvested after a cardiac MRI imaging analysis for biochemical analysis at 150 DPI [16]. Serum samples were obtained from 75 μl of blood collected from the orbital venous sinus (using isoflurane anesthesia) 150 DPI.…”

“…Immunoblot Analysis. Protein analysis was performed as previously described [14,16] using the following antibodies: fatty acid synthase (FAS) Rabbit Polyclonal antibody (1 : 1000 dilution, ab22759) from Abcam Inc. (Cambridge, MA); phospho-ATP-citrate lyase (pACL) (Ser455) Rabbit Polyclonal Antibody (1 : 1000 dilution, #4331), Cell Signaling Technology; AceCS1 (D19C6) Rabbit monoclonal Ab (1 : 1000 dilution #36585), Cell Signaling Technology; Phospho-Acetyl-CoA Carboxylase (pACC) (Ser79) Rabbit Polyclonal Antibody (1 : 1000 dilution #3661), Cell Signaling Technology; anti-CPT1A, mouse monoclonal antibody (CPT1) 1 : 1000 dilution (8F6AE9) (ab128568), Abcam Inc.; Anti-Lipin 1 Rabbit Polyclonal antibody (Lipin 1) 1 : 1000 dilution (ab70138) Abcam Inc.; and Peroxisome Proliferator Activated Receptor Alpha Rabbit Polyclonal antibody (PPARα) 1 : 1000 dilution (PA1-822A), ThermoFisher. Horseradish peroxidase-(HRP-) conjugated goat anti-mouse immunoglobulin (1 : 2000 dilution, Thermo Scientific Catalog #32230) or horseradish peroxidase-(HRP-) conjugated goat anti-rabbit immunoglobulin (1 : 2000 dilution, Thermo Scientific Catalog #31463) was used to detect specific protein bands (explained in the figure legends) using a chemiluminescence system [14].…”

“…When the T. cruzi-infected mice were fed on either a HFD or a RD during the indeterminate stage, i.e., starting after the end of acute infection to late chronic stage (from 35 DPI to 150 DPI), they developed diet-specific ventricular enlargements during chronic infection [16]. These studies in a murine model of chronic Chagas disease established an interesting hypothesis that a long-term HFD treatment causes right ventricular dilation and wall thinning, and a longterm RD treatment results in left ventricular dilation [16]. This suggests that specific diets can alter the metabolic status in the host, which in turn regulates cardiac pathogenesis specific to either left ventricle (LV) or right ventricle (RV).…”