The Role of Dietary Fatty Acids in Metabolic Health

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Background

The overconsumption of long-chain saturated fatty acids in concomitance with the reduction in the intake of unsaturated fatty acids, mainly omega-3s, represents one of the major drivers of the metabolic derangements ascribed to the Western diet, namely obesity and its cardiometabolic complications. Indeed, saturated fatty acids, mainly in the form of long-chain saturated fatty acids (LCSFA), have been shown to disrupt whole body metabolic health by negatively affecting key metabolically active tissues including skeletal muscle, the liver as well as the center for the control of energy balance in the hypothalamus. In these tissues LCSFA trigger metabolic inflammation, mitochondrial dysfunction and endoplasmic reticulum stress, which, in turn, are key pathogenetic mechanisms responsible for promoting metabolic derangements. Particularly, the effects of LCSFA on metabolic health appear to be underpinned by lipotoxicity which was proposed as a key phenomenon linking lipid metabolism to obesity and its comorbidities. However, not all types of fatty acids are detrimental to metabolic health with their chain length and saturation level appearing to dictate their metabolic fate and impact on metabolic health. This aspect may also play a role in shaping the metabolic profile of metabolically healthy vs unhealthy obese individuals, which however remains to be fully investigated. Beside their chemical structure, fatty acid metabolism and their ability to activate intracellular pathways is mediated by proteins governing their transport and trafficking. Thus, defects affecting plasma membrane fatty acid-binding protein and fatty acid translocase may impact upon fatty acid intracellular signaling and energy homeostasis.

In order to develop personalized nutritional interventions to improve metabolic health, it is imperative to explore how dietary fats modulate intracellular metabolism to promote or prevent lipotoxicity and its downstream consequences. It still remains relatively unknown how single or combination of fatty acids, at the cellular level, or dietary patterns differing in lipid composition, at the whole body level, modulate the pathophysiology of obesity and its comorbidities. Thus, this Research Topic aims at gathering together an updated collection of manuscripts reporting on different aspects of fatty acid metabolism, including their ability to promote lipotoxicity, as well as their impact on the pathogenesis of obesity and its comorbidities, and the underlaying molecular mechanisms, including the role of proteins responsible for the uptake, trafficking and metabolism of fatty acids.

In the present Research Topic, we intend to collect original research, reviews, mini-reviews, meta-analysis, case studies, and brief communication articles with the aim to advance our understanding of the role of dietary lipids and their metabolites on metabolic health and, in the case of reviews, provide a clear overview on the state of the art of lipid research in the context of metabolic health. Particularly, this Research Topic welcomes manuscripts in the following areas:
1. Effects of fatty acids on hypothalamic control of energy balance and their role in obesity pathogenesis
2. Molecular mechanisms underpinning the ability of fatty acids to impair or enhance insulin signaling in insulin-tissue targets
3. The role of proteins governing fatty acid uptake and trafficking in metabolic disorders
4. The impact of chain length and saturation level on the intracellular metabolic fate of fatty acids and modulation of lipotoxicity
5. The impact of fatty acids on low-grade chronic inflammation in obesity and its cardiometabolic complications
6. The role of dietary fatty acids in metabolically healthy and unhealthy obesity: from molecular mechanisms to public health aspects
7. The role of fatty acids as modulators of mitochondrial function
8. Novel insights on the role of saturated to polyunsaturated fatty acids dietary ratio in ectopic fat accumulation, liver and cardiovascular health
9. Short chain fatty acids: a link between diet, gut microbiota and lipid metabolism
10. Nutrigenomic impact of varying saturated to polyunsaturated fatty acids dietary ratio in obesity and its comorbidities
11. Genetic determinants of dietary fatty acid metabolism and their impact on metabolic health.

Keywords: Fatty acids, lipotoxicity, insulin resistance, metabolic inflammation, mitochondrial function, obesity, type 2 diabetes, metabolic health

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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