Obese status is associated with accelerated DNA methylation change in peripheral blood of senior dogs

Yamazaki, Jumpei; Meagawa, Shinji; Jelı́nek, Jaroslav; Yokoyama, Shoko; Nagata, Noriyuki; Yuki, Masashi; Takiguchi, Mitsuyoshi

doi:10.1016/j.rvsc.2021.07.024

Cited by 7 publications

(16 citation statements)

References 39 publications

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“…We selected target genomic locations adjacent to 12 genes, namelyGSE1 , VGF , SLC12A5 , SCGN , KCNK12 ,OTUD7A , BCL6B , POU4F2 , ELOVL2 , RALYL ,KISS1R , and CAPS2 (Table 1). The methylation levels of CpG sites adjacent to these genes change with age in humans (Day et al 2013;Florath et al 2014;Bekaert et al 2015;Lowe et al 2018), dogs (Ito et al 2017;Yamazaki et al 2021), and cats (Qi et al 2021). We identified homologous sequences in the genomic regions of brown bears containing the target CpG sites using the Basic Local Alignment Search Tool (BLAST) provided by the National Center for Biotechnology Information.…”

Section: Selection Of Target Genomic Locationsmentioning

confidence: 99%

“…Polymerase chain reaction (PCR) and subsequent pyrosequencing were conducted following previously reported methods (Yamazaki et al 2021). PCR was performed using the TaKaRa EpiTaq HS (for bisulfitetreated DNA) (Takara Bio Inc., Shiga, Japan).…”

Section: Polymerase Chain Reaction and Pyrosequencingmentioning

confidence: 99%

“…In early epigenetic research efforts for age estimation, the focus was on forensic research in humans using various biological samples, including blood, muscle, saliva, buccal swabs, and semen (Horvath 2013;Lee et al 2015;Bekaert et al 2015). Subsequently, similar techniques have been established for laboratory animals such as mice (Wang et al, 2017;Petkovich et al, 2017;Stubbs et al, 2017) and naked mole rats (Heterocephalus glaber ; Lowe et al 2020), companion animals such as dogs and cats (Thompson et al 2017;Qi et al 2021;Raj et al 2021) (Biggar & Storey 2014;Alvarado et al 2015;Yamazaki et al 2021).…”

Section: Introductionmentioning

confidence: 99%

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Age estimation based on blood DNA methylation levels in brown bears

Nakamura

Yamazaki

Matsumoto³

et al. 2023

Preprint

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Age is an essential trait for understanding the ecology and management of wildlife. A conventional method of estimating age in wild animals is counting annuli formed in the cementum of teeth. This method has been used in bears despite some disadvantages, such as high invasiveness and the requirement for experienced observers. In this study, we established a novel age estimation method based on DNA methylation levels using blood collected from 49 brown bears of known ages living in both captivity and the wild. We performed bisulfite pyrosequencing and obtained methylation levels at 39 cytosine-phosphate-guanine (CpG) sites adjacent to 12 genes. The methylation levels of CpGs adjacent to four genes showed a significant correlation with age. The best model was based on DNA methylation levels at just four CpG sites adjacent to a single gene, SLC12A5, and it had high accuracy with a mean absolute error of 1.3 years and median absolute error of 1.0 year after leave-one-out cross-validation. This model represents the first epigenetic method of age estimation in brown bears, which provides benefits over tooth-based methods, including high accuracy, less invasiveness, and a simple procedure. Our model has the potential for application to other bear species, which will greatly improve ecological research, conservation, and management.

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Section: Selection Of Target Genomic Locationsmentioning

confidence: 99%

Section: Polymerase Chain Reaction and Pyrosequencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age estimation based on blood DNA methylation levels in brown bears

Nakamura

Yamazaki

Matsumoto³

et al. 2023

Preprint

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“…In the present study, we found hypermethylation of Kiss1r promoter in the liver of DM2 female rats ( Figure 3b ), which corresponded with lower Kiss1r expression at the protein level ( Figure 3d ). Similarly, hypermethylation of Kiss1r has been reported in peripheral blood DNA of obese dogs [ 19 ]. In the study on dogs, there was a trend towards more profound hypermethylation in male vs. female dogs, whereas we detected altered Kiss1r expression at mRNA and protein level in the liver of females, but not male rats.…”

Section: Discussionmentioning

confidence: 81%

“…Moreover, studies in the last decade suggest that DNA methylation in the regulatory regions of Kiss1 and Kiss1r regulates the expression of these genes both in the context of cancer [ 16 ] and during puberty [ 17 , 18 ]. Recent reports imply a similar epigenetic regulation in diabetes as well [ 19 , 20 ]. For these reasons, we have investigated the DNA methylation status of Kiss1 and Kiss1r promoters in DM2 female rats.…”

Section: Introductionmentioning

confidence: 90%

DNA hypermethylation of Kiss1r promoter and reduction of hepatic Kiss1r in female rats with type 2 diabetes

et al. 2022

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Kisspeptin, produced from the brain and peripheral tissues, may constitute an important link in metabolic regulation in response to external cues, such as diet. The kisspeptin system is well described in the brain. However, its function and regulation in the peripheral tissues, especially in relation to metabolic disease and sex differences, remain to be elucidated. As Kiss1 and Kiss1r , encoding for kisspeptin and kisspeptin receptors, respectively, are altered by overnutrition/fasting and regulated by DNA methylation during puberty and cancer, epigenetic mechanisms in metabolic disorders are highly probable. In the present study, we experimentally induced type 2 diabetes mellitus (DM2) in female Wistar rats using high-fat diet/streptozocin. We analysed expression and DNA methylation of Kiss1 and Kiss1r in the peripheral tissues, using quantitative-reverse-transcription PCR (qRT-PCR) and pyrosequencing. We discovered differential expression of Kiss1 and Kiss1r in peripheral organs in DM2 females, as compared with healthy controls, and the profile differed from patterns reported earlier in males. DM2 in females was linked to the increased Kiss1 mRNA in the liver and increased Kiss1r mRNA in the liver and adipose tissue. However, Kiss1r promoter was hypermethylated in the liver, suggesting gene silencing. Indeed, the increase in DNA methylation of Kiss1r promoter was accompanied by a reduction in Kiss1r protein, implying epigenetic or translational gene repression. Our results deliver novel evidence for tissue-specific differences in Kiss1 and Kiss1r expression in peripheral organs in DM2 females and suggest DNA methylation as a player in regulation of the hepatic kisspeptin system in DM2.

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Fetal origins of obesity: a novel pathway of regulating appetite neurons in the hypothalamus of growth-restricted rat offspring

Han

Song

Shan

et al. 2023

Arch Gynecol Obstet

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Purpose Fetal growth restriction causes a series of sequelae, some of which, such as hyperphagia, reduced satiety and postnatal obesity, are believed to be associated with embryonic hypothalamic neurons impairment. The mechanisms underlying the linkage of fetal brain injuries to break the energy homeostasis have not been elucidated completely. Here, we aim to investigate the effect of intrauterine energy restriction on remodeling appetite neurons in the hypothalamus of fetal and postnatal infant rats. Methods Low-protein (8%) diet combined with 75% energy restriction was used to establish an animal model. Rats offspring brain tissues, harvested from embryo day 18 and postnatal infant day 1, were sampled for dependent regulator analyses and master neuron assessment. Results Growth-restricted rats showed the increased expression of Bsx and NPY in the hypothalamus as well as remodeling hypothalamic neurons differentiation compared to controls. Intriguingly, in cells cultured in vitro test, we found that activated effects of Bsx and NPY could be exacerbated by DNMT1 inhibitor. Conclusions In embryonic and early postnatal stage of FGR rats, we detected high concentrations of orexigenic neurons in the hypothalamus. DNMT1 activity is correlated with early embryonic neurogenesis by mediating the expression of Bsx and NPY. It may be one of the reasons for the abnormal development of the appetite regulation pathway and higher susceptibility to obesity in FGR offspring.

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Obese status is associated with accelerated DNA methylation change in peripheral blood of senior dogs

Cited by 7 publications

References 39 publications

Age estimation based on blood DNA methylation levels in brown bears

Age estimation based on blood DNA methylation levels in brown bears

DNA hypermethylation of Kiss1r promoter and reduction of hepatic Kiss1r in female rats with type 2 diabetes

Fetal origins of obesity: a novel pathway of regulating appetite neurons in the hypothalamus of growth-restricted rat offspring

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