From Nutrigenomics to Functional food and Diet: Insights in Lipid Metabolism

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Schematic representation of the association of Ca2+ and lipid accumulation in steatotic hepatocytes. The proposed mechanism is a positive feedback loop between alteration in Ca2+ homeostasis and formation of cytoplasmic lipid droplet. Alteration in Ca2+ homeostasis promotes lipid synthesis and inhibits lipid degradation. An increase in [Ca2+]i inhibits autophagy of cytoplasmic lipid droplets, and a decrease in SOCE activity causes inhibition of lipolysis, and an increase in [Ca2+]MT inhibits beta-oxidation pathway. In contrast, lipids induce changes in Ca2+ homeostasis through inhibition of SOCE (e.g., Orai) and SERCA2b activities. Lipids also activate InsP3R indirectly and increase the expression of TRPV1.
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The influence of nutrition and environment on human health has been known for ages. Phytonutrients (7,000 flavonoids and phenolic compounds; 600 carotenoids) and pro-health nutrients—nutraceuticals positively add to human health and may prevent disorders such as cancer, diabetes, obesity, cardiovascular diseases, and dementia. Plant-derived bioactive metabolites have acquired an imperative function in human diet and nutrition. Natural phytochemicals affect genome expression (nutrigenomics and transcriptomics) and signaling pathways and act as epigenetic modulators of the epigenome (nutri epigenomics). Transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics are some of the main platforms of complete omics analyses, finding use in functional food and nutraceuticals. Now the recent advancement in the integrated omics approach, which is an amalgamation of multiple omics platforms, is practiced comprehensively to comprehend food functionality in food science.

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Original Research
28 February 2022

Recent years have witnessed a rise in the morbidity of non-alcoholic fatty liver disease (NAFLD), in line with the global outbreak of obesity. However, effective intervention strategy against NAFLD is still unavailable. The present study sought to investigate the effect and mechanism of polyene phosphatidylcholine (PPC), a classic hepatoprotective drug, on NAFLD induced by high fat diet (HFD). We found that PPC intervention reduced the mass of liver, subcutaneous, epididymal, and brown fats in HFD mice. Furthermore, PPC supplementation significantly mitigated liver steatosis and improved glucose tolerance and insulin sensitivity in HFD mice, which was accompanied by declined levels of hepatic triglyceride, serum triglyceride, low density lipoprotein, aspartate aminotransferase, and alanine aminotransferase. Using transcriptome analysis, there were 1,789 differentially expressed genes (| fold change | ≥ 2, P < 0.05) including 893 upregulated genes and 896 downregulated genes in the HFD group compared to LC group. A total of 1,114 upregulated genes and 1,337 downregulated genes in HFD + PPC group were identified in comparison to HFD group. With the help of Gene Ontology (GO) analysis, these differentially expressed genes between HFD+PPC and HFD group were discovered related to “lipid metabolic process (GO: 0006629),” “lipid modification (GO: 0030258),” and “lipid homeostasis (GO: 0055088)”. Though Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found pathways associated with hepatic homeostasis of metabolism and inflammation. Notably, the pathway “Non-alcoholic fatty liver disease (mmu04932)” (P-value = 0.00698) was authenticated in the study, which may inspire the potential mechanism of PPC to ameliorate NAFLD. The study also found that lipolysis, fatty acid oxidation, and lipid export associated genes were upregulated, while the genes in uptake of lipids and cholesterol synthesis were downregulated in the liver of HFD mice after PPC supplementation. Interestingly, PPC attenuated the metabolic inflammation via inhibiting pro-inflammatory macrophage in the livers of mice fed by HFD. In summary, this study demonstrates that PPC can ameliorate HFD-induced liver steatosis via reprogramming metabolic and inflammatory processes, which inspire clues for further clarifying the intervention mechanism of PPC against NAFLD.

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Frontiers in Physiology

Lipids and Wasting Disorders in Disease and Aging
Edited by Lindsay McDermott, Aaron Zefrin Fernandis, Vera C Mazurak
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18 June 2025
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