Fat intake is an important modifiable risk factor for sustainable health and disease management; hence, understanding how lipids are metabolized provides key insight into the molecular pathways that impact physiological homeostasis. Notably, lipid metabolism is genetically regulated, which alters their levels in circulation and tissues, as well as their metabolic fate and incorporation into complex lipid classes. This is eventually reflected in tissue-specific distribution of lipid classes and biomolecule groups, with ultimate health consequences. The tissue-specific lipid patterns involved in human physiology leverage an array of structural and functional properties from a cellular to a systemic level, with some of the main functions being: (1) bioenergetic metabolism reflected in lipid energy storage, expenditure and turn-over (2) lipid-signaling pathways and associated metabolic production of bioactive mediators (3) ligand-binding properties of specific lipids (4) oxido-redox homeostasis (5) membrane remodeling regulating intracellular cascades with a rich spectrum of regulatory implications (6) inflammation (im)balance and initiation or prevention of associated inflammatory responses and (7) mediating immunological responses in viral propagation and bacterial phagocytosis. Consequently, lipid reprogramming in cells and organs is a promising weapon in preventing disease development driven by the metabolic disturbances and lipid pathways. Taken together, the lipid biology is implicated in autoimmune, inflammatory, neurological, cardiovascular, cancer, acute and chronic respiratory and other pathophysiological responses all providing a molecular underpinning of health and disease development.
The lipid-physiological response axis is highly impacted by genetic variation regulating metabolism, the formation of lipoproteins and the production of lipid classes and mediators. To date, the most thoroughly researched genes involved in human lipid metabolism include those: 1) controlling the formation of biologically active long-chain anabolic products such as FADS-fatty acid desaturase gene cluster, SCD-stearoyl-CoA-desaturase and ELOVL-elongase; 2) involved in lipoprotein assembly and metabolic fate including ApoE, ApoB, and LDL-r-LDL receptor; 3) encoding enzymes involved in fatty acid oxygenation and generation of bioactive oxylipins such as COX and LOX, epoxide hydrolase and others; 4) responsible for the synthesis of lipolytic enzymes such as phospholipases isoforms; and 5) encoding for lipid binding transcription factors such as peroxisome proliferator-activated receptor including PPAR-γ gene.
We propose to compile recent advances in this field, especially related to the genetic regulation of fatty acids, complex lipid classes, lipoproteins, and lipid bioactive metabolites with an emphasis of discerning the role of this regulation in acute and chronic disease development and disease prevention and management. We will also emphasize the impact of ancestry-driven genetic variation that has the potential to drive health disparities to further understand disproportionate disease burden in certain populations.
The following research lines are suggested:
1. Effects of genetic variation and gene by diet interactions on lipid metabolism and related chronic diseases, including cardiovascular disease, cancer, liver steatosis, lung and kidney disease
2. Effects of genetic variation and gene by diet interactions on lipid metabolism impacting obesity and associated co-morbidities, as well as disturbed glucose-insulin metabolism
3. Genetic variation and interactions affecting complex lipids and lipid mediator formation
4. Genetic basis of lipid metabolism involved in the progression of acute and chronic infections
5. Genetic architecture and lipid metabolism in different populations of diverse racial and ethnic origin, and how this affects the development of obesity and associated co-morbidities, as well as the progression of chronic diseases and/or acute/chronic infections
6. Implications from in vitro and animal studies in understanding the genetic regulation of lipid metabolism and the production of biomolecules that play a key role in physiological homeostasis.
7. Precision nutrition solutions targeting lipid metabolism in health and disease
Fat intake is an important modifiable risk factor for sustainable health and disease management; hence, understanding how lipids are metabolized provides key insight into the molecular pathways that impact physiological homeostasis. Notably, lipid metabolism is genetically regulated, which alters their levels in circulation and tissues, as well as their metabolic fate and incorporation into complex lipid classes. This is eventually reflected in tissue-specific distribution of lipid classes and biomolecule groups, with ultimate health consequences. The tissue-specific lipid patterns involved in human physiology leverage an array of structural and functional properties from a cellular to a systemic level, with some of the main functions being: (1) bioenergetic metabolism reflected in lipid energy storage, expenditure and turn-over (2) lipid-signaling pathways and associated metabolic production of bioactive mediators (3) ligand-binding properties of specific lipids (4) oxido-redox homeostasis (5) membrane remodeling regulating intracellular cascades with a rich spectrum of regulatory implications (6) inflammation (im)balance and initiation or prevention of associated inflammatory responses and (7) mediating immunological responses in viral propagation and bacterial phagocytosis. Consequently, lipid reprogramming in cells and organs is a promising weapon in preventing disease development driven by the metabolic disturbances and lipid pathways. Taken together, the lipid biology is implicated in autoimmune, inflammatory, neurological, cardiovascular, cancer, acute and chronic respiratory and other pathophysiological responses all providing a molecular underpinning of health and disease development.
The lipid-physiological response axis is highly impacted by genetic variation regulating metabolism, the formation of lipoproteins and the production of lipid classes and mediators. To date, the most thoroughly researched genes involved in human lipid metabolism include those: 1) controlling the formation of biologically active long-chain anabolic products such as FADS-fatty acid desaturase gene cluster, SCD-stearoyl-CoA-desaturase and ELOVL-elongase; 2) involved in lipoprotein assembly and metabolic fate including ApoE, ApoB, and LDL-r-LDL receptor; 3) encoding enzymes involved in fatty acid oxygenation and generation of bioactive oxylipins such as COX and LOX, epoxide hydrolase and others; 4) responsible for the synthesis of lipolytic enzymes such as phospholipases isoforms; and 5) encoding for lipid binding transcription factors such as peroxisome proliferator-activated receptor including PPAR-γ gene.
We propose to compile recent advances in this field, especially related to the genetic regulation of fatty acids, complex lipid classes, lipoproteins, and lipid bioactive metabolites with an emphasis of discerning the role of this regulation in acute and chronic disease development and disease prevention and management. We will also emphasize the impact of ancestry-driven genetic variation that has the potential to drive health disparities to further understand disproportionate disease burden in certain populations.
The following research lines are suggested:
1. Effects of genetic variation and gene by diet interactions on lipid metabolism and related chronic diseases, including cardiovascular disease, cancer, liver steatosis, lung and kidney disease
2. Effects of genetic variation and gene by diet interactions on lipid metabolism impacting obesity and associated co-morbidities, as well as disturbed glucose-insulin metabolism
3. Genetic variation and interactions affecting complex lipids and lipid mediator formation
4. Genetic basis of lipid metabolism involved in the progression of acute and chronic infections
5. Genetic architecture and lipid metabolism in different populations of diverse racial and ethnic origin, and how this affects the development of obesity and associated co-morbidities, as well as the progression of chronic diseases and/or acute/chronic infections
6. Implications from in vitro and animal studies in understanding the genetic regulation of lipid metabolism and the production of biomolecules that play a key role in physiological homeostasis.
7. Precision nutrition solutions targeting lipid metabolism in health and disease