CHRONIC CHAGAS INFECTION SUPPORTS DIABETES

POSADAS MISIONES

Workshop; SUMMER WORSHOP; 2017

Why my research line focus on these topics? (Slide 1) One on hand, Chagas is a neglected disease, endemic in Latin American countries with 6-7 million infected by Trypanosoma cruzi according to World Health Organization 2015.Now, it?s growing concern because inmigrations become to a globalized disease mainly in USA and Europe.(Slide 2) Obesity: Pandemic of the 21st century.WHO estimates that 65% of the world?s population live in a country where overweight and obesity kills more people than underweight. Globally, 44% of diabetes, 23 % of ischeamic heart disease and 7-41% of certain cancers mainly gastrointestinals and mama. The adipocyte hypertrophy causes Hypoxia, Adipocyte cell death, fatty acid release and Inflammatory cytokine release. The chemokyne and cetokynes released attract monocytes to the adipoce tissue and generates a cronic low grade inflammation; this cronic situation produce secondary effects in liver, adipose, inflammatory response activation, impaired insulin signaling, skeletal muscle, insulin resistance and hypothalamus leptin resistance. The principal molecule exclusively secreted by AT is leptin. (Slide 3) Leptin discoverement (1994) changed the paradigm of AT as an inert and specialized organ to storage fat and the emerging view as an endocrine organ with certain immune properties. Hypertrophied adipocytes secret more than 200 molecules with different functions, among them, cytokines, shemokines (MCP-1), and other molecules (leptin and adiponectin) with autocrine and paracrine actionsAT ( adipose tissue) dysfuncional shows crown like structures, which are macrophages around adipocytes dead, not present in homeostatic adipose tissue that shows a pro and anti-inflammatory cytokine balance.AT express on its surface, immune innate receptors like Toll like and scavenger CD 36 involved in insulin resistance and other biologicsl functions. This inflammatory context occurs at both local and systemic level(Slide 4) In healthy state, adipose tissue shows asipocytes of minor size and has an M2 phenotype macrophages with anti-inflammatory functions. By the contrary, M1 or metabolically active macrophages are found in chronic inflamed obesity characterized by hypertrophied cells.(Slide 5) Here, we can see Innate immunity and homeostatic or steri inflammation. Inmune innate system is our first line of defense against microorganism ( for example T. crzi) and metabolic signals genered during metabolic processs among them, Axidized LDL and Fatty free acids. When these stimuli are sensed by immune innate receptors produce and immune metabolic response, which may be exacerbated when different stimulus act in concert.(Slide 6) Challenge?First , we design a novel obesity model induced by diet (DIO) for produce obesity and its co-morbidities that may reflect that situation occu red in the human clinical field . Second, to see the effect of Trypanosoma cruzi, tha causative agent of Chagas disease,(Slide 7) Experimental design ( Four mouse groups)First, Control LFD ( description)Second Diet induced obesity treatment (DIO ( desdription)Thrid, DIO +I ( the same as DIO more T. cruzi infection Finally, LFD + ITimes to study: 4, 12 and 24 weeks.Blood amd tissue samples ResultsSlide 8