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Recent developments on the role of epigenetics in obesity and metabolic disease.

van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL - Clin Epigenetics (2015)

Bottom Line: More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations.In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time.While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease.

View Article: PubMed Central - PubMed

Affiliation: CSIRO Food and Nutrition Flagship, PO Box 52, North Ryde, NSW 1670 Australia.

ABSTRACT
The increased prevalence of obesity and related comorbidities is a major public health problem. While genetic factors undoubtedly play a role in determining individual susceptibility to weight gain and obesity, the identified genetic variants only explain part of the variation. This has led to growing interest in understanding the potential role of epigenetics as a mediator of gene-environment interactions underlying the development of obesity and its associated comorbidities. Initial evidence in support of a role of epigenetics in obesity and type 2 diabetes mellitus (T2DM) was mainly provided by animal studies, which reported epigenetic changes in key metabolically important tissues following high-fat feeding and epigenetic differences between lean and obese animals and by human studies which showed epigenetic changes in obesity and T2DM candidate genes in obese/diabetic individuals. More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations. These studies have also reported epigenetic differences between obese/T2DM adults and healthy controls and epigenetic changes in association with nutritional, weight loss, and exercise interventions. There is also increasing evidence from both human and animal studies that the relationship between perinatal nutritional exposures and later risk of obesity and T2DM may be mediated by epigenetic changes in the offspring. The aim of this review is to summarize the most recent developments in this rapidly moving field, with a particular focus on human EWAS and studies investigating the impact of nutritional and lifestyle factors (both pre- and postnatal) on the epigenome and their relationship to metabolic health outcomes. The difficulties in distinguishing consequence from causality in these studies and the critical role of animal models for testing causal relationships and providing insight into underlying mechanisms are also addressed. In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time. While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease.

No MeSH data available.


Related in: MedlinePlus

Overview of human tissues used for studies into the role of epigenetics in obesity. For each tissue, studies are grouped by study type; epigenome-wide association studies (EWAS) and pre- and postnatal interventions. Numbers represent the reference number
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Fig2: Overview of human tissues used for studies into the role of epigenetics in obesity. For each tissue, studies are grouped by study type; epigenome-wide association studies (EWAS) and pre- and postnatal interventions. Numbers represent the reference number

Mentions: A major limitation in many human studies is that epigenetic marks are often assessed in peripheral blood, rather than in metabolically relevant tissues (Fig. 2). The heterogeneity of blood is an issue, since different cell populations have distinct epigenetic signatures, but algorithms have been developed to estimate the cellular composition to overcome this problem [86]. Perhaps more importantly, epigenetic marks in blood cells may not necessarily report the status of the tissues of primary interest. Despite this, recent studies have provided clear evidence of a relationship between epigenetic marks in blood cells and BMI. In the case of HIF3A for which the level of methylation (beta-value) in the study population ranged from 0.14–0.52, a 10 % increase in methylation was associated with a BMI increase of 7.8 % [52]. Likewise, a 10 % difference in PGC1A methylation may predict up to 12 % difference in fat mass [54].Fig. 2


Recent developments on the role of epigenetics in obesity and metabolic disease.

van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL - Clin Epigenetics (2015)

Overview of human tissues used for studies into the role of epigenetics in obesity. For each tissue, studies are grouped by study type; epigenome-wide association studies (EWAS) and pre- and postnatal interventions. Numbers represent the reference number
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940755&req=5

Fig2: Overview of human tissues used for studies into the role of epigenetics in obesity. For each tissue, studies are grouped by study type; epigenome-wide association studies (EWAS) and pre- and postnatal interventions. Numbers represent the reference number
Mentions: A major limitation in many human studies is that epigenetic marks are often assessed in peripheral blood, rather than in metabolically relevant tissues (Fig. 2). The heterogeneity of blood is an issue, since different cell populations have distinct epigenetic signatures, but algorithms have been developed to estimate the cellular composition to overcome this problem [86]. Perhaps more importantly, epigenetic marks in blood cells may not necessarily report the status of the tissues of primary interest. Despite this, recent studies have provided clear evidence of a relationship between epigenetic marks in blood cells and BMI. In the case of HIF3A for which the level of methylation (beta-value) in the study population ranged from 0.14–0.52, a 10 % increase in methylation was associated with a BMI increase of 7.8 % [52]. Likewise, a 10 % difference in PGC1A methylation may predict up to 12 % difference in fat mass [54].Fig. 2

Bottom Line: More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations.In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time.While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease.

View Article: PubMed Central - PubMed

Affiliation: CSIRO Food and Nutrition Flagship, PO Box 52, North Ryde, NSW 1670 Australia.

ABSTRACT
The increased prevalence of obesity and related comorbidities is a major public health problem. While genetic factors undoubtedly play a role in determining individual susceptibility to weight gain and obesity, the identified genetic variants only explain part of the variation. This has led to growing interest in understanding the potential role of epigenetics as a mediator of gene-environment interactions underlying the development of obesity and its associated comorbidities. Initial evidence in support of a role of epigenetics in obesity and type 2 diabetes mellitus (T2DM) was mainly provided by animal studies, which reported epigenetic changes in key metabolically important tissues following high-fat feeding and epigenetic differences between lean and obese animals and by human studies which showed epigenetic changes in obesity and T2DM candidate genes in obese/diabetic individuals. More recently, advances in epigenetic methodologies and the reduced cost of epigenome-wide association studies (EWAS) have led to a rapid expansion of studies in human populations. These studies have also reported epigenetic differences between obese/T2DM adults and healthy controls and epigenetic changes in association with nutritional, weight loss, and exercise interventions. There is also increasing evidence from both human and animal studies that the relationship between perinatal nutritional exposures and later risk of obesity and T2DM may be mediated by epigenetic changes in the offspring. The aim of this review is to summarize the most recent developments in this rapidly moving field, with a particular focus on human EWAS and studies investigating the impact of nutritional and lifestyle factors (both pre- and postnatal) on the epigenome and their relationship to metabolic health outcomes. The difficulties in distinguishing consequence from causality in these studies and the critical role of animal models for testing causal relationships and providing insight into underlying mechanisms are also addressed. In summary, the area of epigenetics and metabolic health has seen rapid developments in a short space of time. While the outcomes to date are promising, studies are ongoing, and the next decade promises to be a time of productive research into the complex interactions between the genome, epigenome, and environment as they relate to metabolic disease.

No MeSH data available.


Related in: MedlinePlus