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The effect of different types of fatty acids associated to low carbohydrate diet on inflammatory, epigenetic and mitochondrial modulation on Obesity treatment

Grant number: 20/04448-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2021
Effective date (End): January 31, 2023
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal researcher:Luciana Pellegrini Pisani
Grantee:Aline Boveto Santamarina
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil


Recent WHO data show that chronic non-communicable diseases such as Obesity represent the main cause of mortality worldwide. In view of this, an incessant search for nutritional intervention strategies has grown, highlighting the models of Low Carbohydrate and High-Fat diet (LCHF). However, the processes involved in the weight loss process, as well as the impact of the type of fatty acid consumed on diet are scarce. The typical imbalance in the quality of lipids in the Western diet promotes the adaptation of the membrane phospholipid mechanism by anchored membrane receptors and their function. A relevant marker impacted by the composition of the diet, in particular LCHF, are the epigenetic mechanisms, which can influence the metabolic and inflammatory pathways, as well as promote mitochondrial biogenesis and reduce adipogenesis. Hormonal factors related to Obesity such as leptin and adiponectin, lipid metabolism and mitochondrial function are closely influenced by diet-mediated epigenetic factors. Thus, this study aims to investigate the quality of the lipids in the diet consumed by the LCHF strategy, which affects the cellular processes of lipid metabolism and mitochondrial activity, as well as epigenetics, modulating the homeostasis process. To do so, we will evaluate in obese adult animals consuming a control diet or LCHF associated with different types of fatty: body weight gain and food intake; adiposity; serum triacylglycerol, glucose, total cholesterol, HDL, LDL and fatty acids profile. Global DNA methylation; HDAC enzyme activity; protein expression of DNMT1, DNMT3a, DNMT3b, MeCP2, OXPHOS, p-AMPK, SIRT1, PGC-1a, AdipoR2, UCP-1; and IL-1², IL-6, TNF-± and IL-10 content; the content of mitochondrial DNA and polarization of resident macrophages. Summarizing, we hypothesize that the LCHF diet, as well as adopting a healthy diet pattern, will promote weight loss. Additionally, identify whether the quality of the lipids can modify the functionality of the membrane, modular epigenetic mechanisms, reflect on the polarization of macrophages, oxidative stress and insulin resistance, since the association of LCHF and different sources of lipids on the above is scarce or absent from the scientific literature. (AU)