The Role of Dietary Fatty Acids on Immune Function in the Context of Obesity
Creators: Gonzalez Hernandez, Carolina
Publisher: name: University of Alberta Library
Year: 2024

<p>Obesity is a major public health problem since it is associated with different complications, including cardiovascular diseases, cancer, type 2 diabetes (T2D), and a higher risk of infections. This is due in part to the fact that obesity is characterized by the presence of chronic low-grade systemic inflammation, which alongside the consumption of a high-fat diet (HFD) and the development of insulin resistance may lead to immune dysfunction.<br>
Fatty acids (FAs) are known for having immunomodulatory properties. Saturated fatty acids (SFAs) are considered pro-inflammatory since they can directly bind to the Toll-like receptor 4 (TLR4). In the case of polyunsaturated fatty acids (PUFAs), omega 6 (n-6) are recognized to contribute to inflammation, whereas omega 3 (n-3) facilitate the resolution of inflammation. Conversely, monounsaturated fatty acids (MUFAs) are considered more neutral regarding their immunomodulatory effects. Therefore, the objective of this thesis is to investigate the role that dietary FAs have on immune function in the context of obesity.<br>
In our first study, we evaluated the effects of a high MUFA diet on peripheral immune function (spleen) in the context of a diet-induced obesity (DIO) rat model. Male Sprague Dawley rats 6-weeks-old were consuming either a low-fat high carbohydrate diet (HC) (24% calories from fat), a standard high-fat diet (HF) (providing 35% calories from fat), or a high-fat diet with olive oil (HFOO) high in MUFA (providing 35% calories from fat where 33% of the fat mixture was replaced by olive oil). During the first 3 weeks, HC and HF diets were used to induce obesity. After that time, animals in the HC group continued receiving the same diet, and those fed the HF diet were randomized to either continue on the same HF control diet or to receive the HFOO for an additional 4 weeks. We observed that MUFA reduced the production of pro-inflammatory cytokines after T cell stimulation, specifically by reducing Tumor Necrosis Factor Alpha (TNF-α), and interleukin (IL)-6, with a trend towards a reduction in Interferon-gamma (IFN-γ). However, there was no effect on antigen-presenting cells (APC) function. In addition to that, HFOO significantly diminished the secretion of IL-2 after concanavalin A (ConA) stimulation compared to HF, suggesting a reduction in T cell proliferation.<br>
In our second study, we explored the relationship between dietary FAs and immune function in people living with obesity and with and without metabolic complications. Data from the Nutrition and Immunity (NutrIMM) study was used. In this study, participants were allocated into one of four groups depending on their metabolic phenotype: Lean-normoglycemic (Lean), Obese-normoglycemic (Obese-NG), Obese-glucose intolerant (Obese-GI), Obese with type 2 diabetes (Obese-T2D), and subsequently were fed a North American diet for 4 weeks. At baseline, our results found that the proportions of SFAs and MUFAs in plasma increased across groups, while PUFAs decreased. Additionally, SFAs in plasma, particularly palmitic acid, were positively associated with the production of IL-1B from APCs after stimulation. Plasma MUFAs were not associated with changes in the production of pro-inflammatory cytokines following stimulation. No significant association was found with n-3; however, PUFAs, especially linoleic acid, were negatively associated with the secretion of IL-1B by APC after LPS stimulation.<br>
In this research we concluded that SFAs exhibited pro-inflammatory effects, MUFAs did not show a direct relationship with the production of pro-inflammatory cytokines after immune cell stimulation on their own; however, when replacing SFAs, MUFAs displayed anti-inflammatory properties by decreasing T helper (Th) 1 response and diminishing IL-2 secretion after ConA stimulation. PUFAs, particularly linoleic acid, were found to also exert anti-inflammatory properties. Therefore, it is recommended to avoid the consumption of high SFAs such as those high in the North American diet, which may contribute to chronic low-grade systemic inflammation and immune dysfunction, and to prefer the consumption of diets high in MUFAs and PUFAs such as the Mediterranean diet.</p>