Non‐alcoholic fatty liver disease: the role of nuclear receptors and circadian rhythmicity

Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Oben, Jude A.; Tarquini, Roberto; Cosmo, Salvatore De

doi:10.1111/liv.12534

Cited by 60 publications

(51 citation statements)

References 248 publications

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“…In addition, in CD and UC patients we found down-regulation of PCK1, encoding soluble phosphoenolpyruvate carboxykinase 1, PCK2, encoding mithocondrial phosphoenolpyruvate carboxykinase 2, HMGCR, encoding 3-hydroxy-3methylglutaryl-CoA reductase, and up-regulation of PKM2, encoding muscle pyruvate kinase. The altered expression of genes encoding enzymes involved in glucose, lipid, and mitochondrial oxidative metabolism suggests derangement of metabolic pathways in the diseased intestinal mucosa of IBD that could play a key role in the pathogenetic mechanisms (Mazzoccoli et al, 2012b(Mazzoccoli et al, , 2014aVinciguerra et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome

Palmieri¹,

Mazzoccoli

Bossa³

et al. 2015

Chronobiology International

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Simultaneous analysis of the transcripts of thousands of genes by cDNA microarrays allows the identification of genetic regulatory mechanisms involved in disease pathophysiology. The circadian clock circuitry controls essential cell processes and the functioning of organ systems, which are characterized by rhythmic variations with 24-hour periodicity. The derangement of these processes is involved in the basic mechanisms of inflammatory, metabolic, degenerative and neoplastic diseases. We evaluated by genome-wide cDNA microarray analysis the transcriptome of endoscopic mucosal biopsies of patients with inflammatory bowel diseases (IBD) focusing on the expression of circadian genes in Crohn's disease (CD) and ulcerative colitis (UC). Twenty-nine IBD patients (15 with CD and 14 with UC) were enrolled and mucosal biopsies were sampled at either inflamed or adjacent non-inflamed areas of the colon. A total of 150 circadian genes involved in pathways controlling crucial cell processes and tissue functions were investigated. In CD specimens 50 genes were differentially expressed, and 21 genes resulted up-regulated when compared to healthy colonic mucosa. In UC specimens 50 genes were differentially expressed, and 27 genes resulted up-regulated when compared to healthy colonic mucosa. Among the core clock genes ARNTL2 and RORA were up-regulated, while CSNK2B, NPAS2, PER1 and PER3 were down-regulated in CD specimens. Conversely, ARNTL2, CRY1, CSNK1E, RORA and TIPIN were up-regulated, while NR1D2 and PER3 were down-regulated in UC. In conclusion, in CD and UC patients there are differences in the expression of circadian genes between normal and diseased intestinal mucosa. The deregulated genes evidenced by transcriptome analysis in the major IBDs may play a crucial role in the pathophysiological mechanisms and may suggest novel therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome

Palmieri¹,

Mazzoccoli

Bossa³

et al. 2015

Chronobiology International

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“…These clocks drive the temporal variations of expression of genes encoding proteins involved in lipid and glucose metabolism (biosynthesis, transport, binding and lysis). 44,45 The expression of a huge number of these genes is influenced by the presence of macroH2A1 variants 17,20 and shows an evident circadian rhythmicity of variation, with the exception of Apoa1, which is characterized by ultradian rhythmicity (period o20 h) (Supplementary Table S1). Despite the gross analysis of energy expenditure did not indicate major alterations in macroH2A1 KO mice, the assessment of gene expression in BAT revealed coordinated induction of marker genes of enhanced mitochondrial thermogenesis and glucose consumption, consistently with enhanced BAT-mediated energy expenditure in these mice.…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet

et al. 2014

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“…65 Liver metabolic pathways are regulated by circadian biological clocks, and hepatic health is maintained by proper timing of circadian patterns of metabolic gene expression, with the alternation of anabolic processes corresponding to the feeding/active state during wakefulness, and catabolic processes characterizing the fasting/resting state during sleep. 66 …”

Section: Dysregulated Circadian Metabolism In Nafldmentioning

confidence: 99%

Interaction between stress responses and circadian metabolism in metabolic disease

et al. 2017

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Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Dysregulated circadian rhythms are closely associated with various human metabolic diseases, including type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease. Modern lifestyles are frequently associated with an irregular circadian rhythm, which poses a significant risk to public health. While the central clock has a set periodicity, circadian oscillators in peripheral organs, particularly in the liver, can be entrained by metabolic alterations or stress cues. At the molecular level, the signal transduction pathways that mediate stress responses interact with, and are often integrated with, the key determinants of circadian oscillation, to maintain metabolic homeostasis under physiological or pathological conditions. In the liver, a number of nuclear receptors or transcriptional regulators, which are regulated by metabolites, hormones, the circadian clock, or environmental stressors, serve as direct links between stress responses and circadian metabolism. In this review, we summarize recent advances in the understanding of the interactions between stress responses (the endoplasmic reticulum (ER) stress response, the oxidative stress response, and the inflammatory response) and circadian metabolism, and the role of these interactions in the development of metabolic diseases.

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Non‐alcoholic fatty liver disease: the role of nuclear receptors and circadian rhythmicity

Cited by 60 publications

References 248 publications

Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome

Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome

Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet

Interaction between stress responses and circadian metabolism in metabolic disease

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