PA-supplementation leads to perturbed expression of genes associated with lipid metabolism, ER stress and unfolded protein response. Relative mRNA expression of (A) Lipid metabolism associated genes (n = 4), (B) ER stress associated genes (n = 4) and (C) Unfolded Protein Response-associated genes (n = 4) and (D) Oxidative phosphorylation genes in adult (n = 5) control and PA-fed groups. (E) Genes associated with fatty acid oxidation (n = 3) and (F) Genes associated with inflammation and antioxidant response system (n = 3). (G) Relative fold change in the intensity of DCFDA fluorescence in PA-Fed group in comparison to control (n = 3). Values are given as mean ± SEM. Student’s t test was performed to determine statistical significance. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (H) Flowchart showing dysregulation of metabolic and stress pathways upon PA-supplementation resulting in MAFLD progression. acc, acetyl-CoA carboxylase; fasn, fatty acid synthase; hmgcs1, 3-hydroxy-3-methylglutaryl-CoA synthase 1; hmgcra, 3-hydroxy-3-methylglutaryl-CoA reductase; scd, stearoyl- CoA desaturase; atf6, activating transcription factor 6; xbp1, X-box binding protein 1; gadd45a, growth arrest and DNA-damage-inducible gene 45 alpha; ddit3, DNA damage-inducible transcript 3; il1β, interleukin-1β; hspd1, heat shock 60 protein 1; hspa9, heat shock protein 9; clpp, caseinolytic mitochondrial matrix peptidase proteolytic subunit; lonp1, lon peptidase 1; uqcrc2, cytochrome b-c1 complex subunit 2, mitochondrial; cox4i1, cytochrome c oxidase subunit 4 isoform 1, mitochondrial, atp5f1b; ATP synthase subunit beta, mitochondrial, sdha; succinate dehydrogenase, cpt1a; carnitine palmitoyl transferase 1, acadm; medium-chain specific acyl-CoA dehydrogenase, mitochondrial, pparg; peroxisome proliferator-activated receptor gamma, pparab; peroxisome proliferator-activated receptor alpha b, il8; interleukin 8, tgfβ; transforming growth β, gpx1a; glutathione peroxidase 1a.
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