Abstract
Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. A novel diet-induced obesity model (DIO) was developed in C57BL/6 wild type mice to examine the effect of chronic infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia, and cardiac/hepatic steatosis were strongly developed in DIO mice. Strikingly, although these metabolic alterations were collectively improved by infection, plasmatic apoB100 levels remain significantly increased in DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4−/− mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression.
Highlights
The recognition of obesity as a main source of human disease including type 2 diabetes (T2D) and cardiovascular disorders, has provoked fierce interest in metabolic dysfunction, and identified inflammatory insulin resistance (IR) as its central pathophysiological mechanism [1]
To determinate whether medium fat diet (MFD), low fructose and a minimal streptozotocin (STZ) dose could develop a non-drastic diet-induced obesity model (DIO) model, we first assessed the variation of morphometric parameters in DIO group compared to low fat diet (LFD) group for 24 weeks
The effect of T. cruzi infection in this DIO model (DIO+I) showed a significant reduction in body weight, waist diameter and VAT content compared to DIO group (Figure 1A-1D), and no significant differences were seen between DIO+I and LFD+I groups
Summary
The recognition of obesity as a main source of human disease including type 2 diabetes (T2D) and cardiovascular disorders, has provoked fierce interest in metabolic dysfunction, and identified inflammatory insulin resistance (IR) as its central pathophysiological mechanism [1]. Pathogenic responses to obesity have been ascribed to AT dysfunction that promotes the secretion of a large panel of cytokines and chemokines, and leads to the initiation of pro-inflammatory events, oxidative stress and tissue dysfunction [6]. This process involves the coordinated interaction of various cell populations comprising the AT stromal vascular fraction www.impactjournals.com/oncotarget (SVF) including AT macrophages (ATMs), which have received a great deal of attention due to their progressive accumulation during tissue expansion [5, 7]. The general consensus in the field is that obesity induces the polarization from M2 into M1 phenotype [7], several lines of evidence have pointed to a predominant and dynamic M2 polarization of ATMs during obesity in mice and humans [7, 9,10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
