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Early Life Nutrition, Epigenetics, and Later Cardiometabolic Health
Published in Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss, Nutrition and Cardiometabolic Health, 2017
Mark H. Vickers, Clare M. Reynolds, Clint Gray, Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss
While the evidence for the role of epigenetic processes in developmentally programmed metabolic inflammatory disease is limited, there are several studies that implicate poor maternal nutrition in the development of chronic low-grade inflammation and subsequent metabolic disease. Reynolds et al. demonstrated that moderate maternal global undernutrition resulted in increased adipose tissue inflammation, which is linked to insulin resistance in Sprague-Dawley rats (Reynolds et al. 2013a). This study was followed up with evidence that bone marrow macrophages from undernourished offspring have an increased inflammatory profile upon immune stimulation and demonstrate signs of polarization from the anti-inflammatory M2 phenotype to the pro-inflammatory M1 phenotype (Reynolds et al. 2013b). Interestingly, macrophage polarization is a process that is heavily governed by epigenetics, whereby demethylases act on histones that bind to the promoters of genes that characterize the M2 phenotype. Therefore, it is plausible that the effects observed in offspring from undernourished mothers may, in part, be mediated by epigenetic alterations (Satoh et al. 2010). Indeed, inflammatory changes are also observed in relation to maternal obesity. Li et al. demonstrate that maternal obesogenic diets (rich in sugars and fat) program hepatic inflammation in rat neonates, prior to the onset on overt metabolic disease (Li et al. 2013). However, whether these effects are due to direct exposure in utero or via epigenetic changes remains to be examined. A recent study examining transgenerational HFD-induced programming observed progressive increases in infiltrating macrophages across generations accompanied by increased gene expression of critical innate immune mediators such as NLRP4 and TLR2/4 in adipose tissue. These findings were associated with the hypomethylation of inflammatory gene promoter regions, thus demonstrating evidence of transgenerational epigenetic transmission of meta-inflammation (Ding et al. 2014).
TLRs/NLRs: Shaping the landscape of host immunity
Published in International Reviews of Immunology, 2018
Komal Dolasia, Manoj K Bisht, Gourango Pradhan, Atul Udgata, Sangita Mukhopadhyay
The NLR proteins are intracellular cytoplasmic sensors conserved throughout the plant and animal kingdoms. Although they are primarily expressed in macrophages and other antigen presenting cells, they are also expressed in lymphocytes and non-immune cells. This family has 23 members with similar tripartite structure consisting of a C-terminal leucine-rich repeat (LRR) domain that bind ligands, a central nucleotide-binding domain (NACHT domain) which is critical for self-oligomerization, and a variable N-terminal domain.8 NLRs are subdivided on the basis of amino-terminal domain,9 such as (i) NLRA, A for acidic transactivating domain which includes CIITA, (ii) NLRB, B for BIRs (baculovirus inhibitor repeat motif), the only member of this family is NAIP, (iii) NLRC, where C stands for CARD (caspase recruitment domain) which includes NOD1, NOD2, NLRC3 (NLR family CARD domain-containing protein 3), NLRC4 (Ipaf), NLRC5 and iv) NLRP, where P stands for a pyrin (PYD). This group contains NLRP1 (NLR Family Pyrin Domain Containing 1), NLRP2, NLRP3, NLRP4, NLRP5, NLRP6, NLRP7, NLRP8, NLRP9 and NLRP10.10,11