Cofactors As Metabolic Sensors Driving Cell Adaptation in Physiology and Disease

Abstract

Chromatin architectures and epigenetic fingerprint regulation are fundamental for genetically determined biological processes. Chemical modifications of the chromatin template sensitize the genome to intracellular metabolism changes to set up diverse functional adaptive states. Accumulated evidence suggests that the action of epigenetic modifiers is sensitive to changes in dietary components and cellular metabolism intermediates, linking nutrition and energy metabolism to gene expression plasticity. Histone posttranslational modifications create a code that acts as a metabolic sensor, translating changes in metabolism into stable gene expression patterns. These observations support the notion that epigenetic reprograming-linked energy input is connected to the etiology of metabolic diseases and cancer. In the present review, we introduce the role of epigenetic cofactors and their relation with nutrient intake and we question the links between epigenetic regulation and the development of metabolic diseases.

Emerging concepts on the role of epigenetics in the relationships between nutrition and health

“…Human genetic variation amongst individuals can influence the epigenetic architecture and its responsiveness to changes in nutrient exposures and metabolic activity . Methylation is amongst the best characterized epigenetic marks with respect to its effect on genome function as well as its relationship to nutrition and other environmental exposures . Both histone tails and cytosine bases within DNA are subject to modification by methylation, and both are tightly linked and interact through the structure of the chromatin .…”

Effect of supplementing chromium histidinate and picolinate complexes along with biotin on insulin sensitivity and related metabolic indices in rats fed a high‐fat diet

“…Nutrition plays a crucial role in the development of cancer, cardiovascular diseases, and diabetes (Rabhi, Hannou, Froguel, & Annicotte, ). Feeding a high‐fat diet (HFD) to experimental animals exerts a number of adverse metabolic alterations including hypertriglyceridemia, hyperinsulinemia, and glucose intolerance (Buchanan, Youn, Campese, & Sipos, ; Nascimento et al., ).…”

Metabolism and Epigenetic Interplay in Cancer: Regulation and Putative Therapeutic Targets

“…Moreover, amino acid transporters overexpression by cancer cells may directly increase methionine uptake ( Fuchs and Bode, 2005 ; Haase et al, 2007 ). Likewise, serine is also in high demand by cancer cells, contributing to increased ATP availability in cancers cells and provision of SAM, which is synthesized from methionine ( Rabhi et al, 2017 ). Interestingly, increased methylthioadenosine (MTA) concentration in cancer cells harbouring 5-methylthioadenosine phosphorylase (MTAP) deletions results in decreased H4R3me2 mark and, consequently, arginine methyltransferase 5 (PRMT5) inhibition ( Kryukov et al, 2016 ).…”

“…Both JMJDs and TETs are dioxygenases dependent of α-ketoglutarate (α-KG) as co-factor (Figure 4 ), being inhibited by TCA cycle intermediates succinate and fumarate ( Xiao et al, 2012 ): α-KG is produced from isocitrate by mitochondrial enzymes isocitrate dehydrogenase 2 (IDH2) and 3 (IDH3) as an intermediary of TCA cycle. In addition to isocitrate, α-KG is also synthetized from amino acids such as arginine, glutamine, histidine and proline (Figure 4 ) ( Etchegaray and Mostoslavsky, 2016 ; Rabhi et al, 2017 ; Kim and Yeom, 2018 ). The α-KG/succinate ratio regulates chromatin status in embryonic stem cells (ESCs) through JMJD3 and Tet1/Tet2 demethylation of H3K9me3, H3K27me3 and H4K20me ( Carey et al, 2015 ).…”

“…After glucose, glutamine is the main acetyl-CoA source in tumour cells. In glucose deprivation, glutamine is used as substrate and acetyl-CoA production in TCA cycle favours histone acetylation, stimulating tumour cell proliferation and growth ( Le et al, 2012 ; Lu and Thompson, 2012 ; McDonnell et al, 2016 ; Rabhi et al, 2017 ).…”