biostudies-literatureUnknown9(12)Hauck AKOxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obAntioxidants (Basel, Switzerland)E1210https://www.ebi.ac.uk/biostudies/studies/S-EPMC7761391biostudies-literatureHistone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging.PMC7761391Bernlohr DAZhou THauck AKChen YUpadhyay ASun YO'Connor MBfalseHistone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging.Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from ob2020-01-01T00:00:00Z2020 Dec2025-04-18T17:42:51.903Z2021-02-20T16:41:22ZS-EPMC77613913327180610.3390/antiox9121210