Jenneffer Rayane Braga Tibaes | ALES Graduate Seminar

Event details: A graduate exam seminar is a presentation of the student’s final research project for their degree.
This is an ALES PhD Final Exam Seminar by Jenneffer Rayane Braga Tibaes. This seminar is open to the general public to attend.

PhD with Dr. Caroline Richard.

Zoom Link: https://ualberta-ca.zoom.us/j/94845323313?pwd=MmawgRmg20HbwnHtWF0HtaiJz8cDFw.1

Thesis Topic: Independent Contribution of Glycemia and Obesity to Immune Dysfunction

Abstract: 

Obesity is a major public health concern, contributing to a range of metabolic disorders such as type 2 diabetes (T2D), cardiovascular diseases, and immune dysfunction. One of the main factors linking obesity to these complications is the presence of chronic low-grade systemic inflammation, which is exacerbated by hyperglycemia and insulin resistance. These conditions alter immune responses and increase susceptibility to infections and inflammation-related diseases. This thesis aimed to examine the distinct effects of obesity and glycemic control on immune function, considering the influence of biological sex.

Through a bench-to-bedside approach, we first examined the effects of a high-fat diet (HFD) on immune function in male and female Wistar rats. Our findings demonstrated that males exhibited greater immune dysfunction, with reduced IL-2 production and impaired T-cell responses, whereas females displayed more robust immune responses, potentially due to a combination of a milder obesity phenotype and protective immune mechanisms. Expanding upon these findings, we conducted a systematic review of sex differences in immune function across diet-induced obesity models, which confirmed that females generally exhibited lower levels of systemic inflammation and a higher proportion of anti-inflammatory M2 macrophages, while males showed a predominance of pro-inflammatory M1 macrophages. Despite these differences, both sexes experienced immune dysfunction associated with obesity, highlighting the complexity of these interactions. However, immune function was only directly evaluated in 7% of the studies reviewed, limiting the ability to draw comprehensive conclusions. In a clinical trial, we explored immune function in individuals with obesity and varying levels of glycemic control through the Nutrition and Immunity (NutrIMM) study. We compared immune responses across groups with normoglycemia, glucose intolerance, and T2D. Individuals with obesity and T2D demonstrated the most severe immune dysfunction, including elevated markers of systemic inflammation such as C-reactive protein (CRP) and impaired T-cell function as measured by low secretion of interleukin-2 upon phytohemagglutinin stimulation and cell proliferation. Interestingly, sex differences were observed in inflammatory responses, with females showing higher baseline CRP levels and males exhibiting more pronounced pro-inflammatory cytokine secretion following immune stimulation including IFN-ɣ, IL-1β, and TNF-α.

In conclusion, this thesis demonstrates the independent and combined effects of glycemia and obesity on immune function, emphasizing the role of biological sex in shaping immune responses. These findings highlight the need for personalized interventions that consider both metabolic health and sex-specific factors to address immune dysfunction in obesity and metabolic diseases.