Single-nucleotide polymorphisms and DNA methylation markers associated with central obesity and regulation of body weight

Goñi, Leticia; Milagro, Fermı́n I.; Cuervo, Marta; Martínéz, J. Alfredo

doi:10.1111/nure.12143

Cited by 33 publications

(16 citation statements)

References 168 publications

(239 reference statements)

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“…The latter is regulated at several levels, allowing transcriptional plasticity. For instance, epigenetic marks such as DNA methylation are intensely investigated for their causal and associative role in the determination of body mass index (BMI) [2–4]. A recently emerged alternative mechanism of transcriptional plasticity is the replacement of canonical histones, around which DNA is wrapped (H2A, H2B, H3 and H4), with the incorporation of histone variants, mostly of histones H2A or H3 [5–7].…”

Section: Introductionmentioning

confidence: 99%

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Pazienza

Panebianco

Rappa

et al. 2016

Epigenetics & Chromatin

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BackgroundObesity has tremendous impact on the health systems. Its epigenetic bases are unclear. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, regulating cell plasticity and proliferation, during pluripotency and tumorigenesis. Their role in adipose tissue plasticity is unknown.ResultsHere, we show evidence that macroH2A1.1 protein levels in the visceral adipose tissue of obese humans positively correlate with BMI, while macroH2A1.2 is nearly absent. We thus introduced a constitutive GFP-tagged transgene for macroH2A1.2 in mice, and we characterized their metabolic health upon being fed a standard chow diet or a high fat diet. Despite unchanged food intake, these mice exhibit lower adipose mass and improved glucose metabolism both under a chow and an obesogenic diet. In the latter regimen, transgenic mice display smaller pancreatic islets and significantly less inflammation. MacroH2A1.2 overexpression in the mouse adipose tissue induced dramatic changes in the transcript levels of key adipogenic genes; genomic analyses comparing pre-adipocytes to mature adipocytes uncovered only minor changes in macroH2A1.2 genomic distribution upon adipogenic differentiation and suggested differential cooperation with transcription factors. MacroH2A1.2 overexpression markedly inhibited adipogenesis, while overexpression of macroH2A1.1 had opposite effects.ConclusionsMacroH2A1.2 is an unprecedented chromatin component powerfully promoting metabolic health by modulating anti-adipogenic transcriptional networks in the differentiating adipose tissue. Strategies aiming at enhancing macroH2A1.2 expression might counteract excessive adiposity in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-016-0098-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Pazienza

Panebianco

Rappa

et al. 2016

Epigenetics & Chromatin

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“…However, individual responses to body weight loss interventions vary widely and several studies have aimed to identify psychological, behavioral and personal predictors of this variability [4,5,6]. In this context, genetic factors have been described to be associated with adiposity and body weight control, since there are diverse genes involved in the regulation of energy expenditure, appetite, thermogenesis, adipogenesis, insulin resistance and lipid metabolism [7,8,9]. …”

Section: Introductionmentioning

confidence: 99%

Gene-Gene Interplay and Gene-Diet Interactions Involving the <b><i>MTNR1B </i></b>rs10830963 Variant with Body Weight Loss

et al. 2014

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Background/Aims: Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions. Methods: 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System. Results: After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant. Conclusions: Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake.

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“…The relationship between DNA methylation and weight loss, excess body weight, or adiposity outcomes has been studied. Given the development of new sequencing and omics technologies, significantly more knowledge on epigenomics of obesity and body fat distribution will emerge in the near future (49).…”

Section: Long-term Implicationsmentioning

confidence: 99%

Obesity: epigenetic aspects

Kaushik

Anderson

2016

Biomolecular Concepts

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Epigenetics, defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence has been shown to play an important role in the etiopathogenesis of obesity. Obesity is associated with extensive gene expression changes in tissues throughout the body. Epigenetics is emerging as perhaps the most important mechanism through which the lifestyle-choices we make can directly influence the genome. Considerable epidemiological, experimental and clinical data have been amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. In addition to the ‘maternal’ interactions, there has been increasing interest in the epigenetic mechanisms through which ‘paternal’ influences on offspring development can be achieved. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations through the transgenerational inheritance of epigenetic traits. Overall, significant progress has been made in the field of epigenetics and obesity and the first potential epigenetic markers for obesity that could be detected at birth have been identified. Fortunately, epigenetic phenomena are dynamic and rather quickly reversible with intensive lifestyle changes. This is a very promising and sustainable resolution to the obesity pandemic.

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Single-nucleotide polymorphisms and DNA methylation markers associated with central obesity and regulation of body weight

Cited by 33 publications

References 168 publications

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Gene-Gene Interplay and Gene-Diet Interactions Involving the <b><i>MTNR1B </i></b>rs10830963 Variant with Body Weight Loss

Obesity: epigenetic aspects

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