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Molecular Biology of Human Obesity: Non-epigenetics in Comparison with Epigenetic Processes

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Handbook of Nutrition, Diet, and Epigenetics

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Abstract

The rapid increase in the prevalence of obesity worldwide is undoubtedly linked to a “social globalization”; however, a genetic component also accounts for individual differences in the predisposition to weight gain. The contribution of candidate gene studies identified several mutations related to obesity in the leptin/melanocortin pathway , which is involved in the regulation of food intake and energy expenditure. Other studies including genome-wide association study (GWAS) found genetic variants across the genome associated with the susceptibility risk to develop obesity. However, until now, all these genetic variations explain only a small fraction of the estimated heritability of obesity. Furthermore, our genome is not likely to change profoundly through mutations in few generations as to explain the rapid increase in the prevalence of obesity. More recently, epigenetic regulation of gene expression emerged as a potential factor that might explain differences in obesity risk. Several genes have been found whose expression is controlled by epigenetic factors. Diet and nutrition appear to be the most important factors influencing epigenetic mechanisms leading to an obese phenotype. Effectively, our diet suffered drastic changes in the last decades with the incorporation of new nutrients and bioactive molecules. Several studies performed both in humans and animal models found differences at different epigenetic mechanisms between obese and non-obese individuals. However, our knowledge on which and how nutrients affect epigenetic mechanisms remains limited. Currently, it is thought that the obesity condition might be a consequence of an interplay between genetic, epigenetic, and lifestyle factors. In the near future, studies based on alterations on gene expression due to environmental signals will help to draw a more complete picture of the obesity etiology.

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Abbreviations

α-MSH:

Alpha-melanocyte-stimulating hormone

AHRR:

Aryl-hydrocarbon receptor repressor

Avy :

Yellow agouti allele

BDNF:

Brain-derived neurotrophic factor

BMI:

Body mass index

cAMP:

Cyclic adenosine monophosphate

CH3 :

Methyl group

CNS:

Central nervous system

CNVs:

Copy number variations

CpG:

5′—C—phosphate—G—3′

DNA:

Deoxyribonucleic acid

Dnmt:

DNA methyltransferases

DOHaD:

Developmental origins of health and disease

GWAS:

Genome-wide association study

HIF3A:

Hypoxia-inducible factor 3 alpha subunit

LEP:

Leptin

LEPR:

Leptin receptor

MC4R:

Melanocortin 4 receptor

NNMT:

Nicotinamide N-methyltransferase

NPY:

Neuropeptide Y

NTRK2:

Neurotrophic receptor tyrosine kinase 2

PCSK1:

Proprotein convertase subtilisin/kexin type 1

POMC:

Pro-opiomelanocortin

PWS:

Prader-Willi syndrome

RNA:

Ribonucleic acid

SIM1:

Single-minded homolog 1

TrkB:

Tropomyosin receptor kinase B

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Authors and Affiliations

  1. Department of Life Sciences, Research Centre for Anthropology and Health (CIAS), University of Coimbra, Calçada Martim de Freitas (edifício de São Bento), 3000-456, Coimbra, Portugal

    David Albuquerque & Licínio Manco

  2. Department of Biomedical Sciences and Medicine, Center for Biomedical Research (CBMR), University of Algarve, 8005-139, Faro, Portugal

    Clévio Nóbrega

  3. Center for Neuroscience and Cell Biology, University of Coimbra, 3000-504, Coimbra, Portugal

    Clévio Nóbrega

Authors
  1. David Albuquerque
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  2. Licínio Manco
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  3. Clévio Nóbrega
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Correspondence to David Albuquerque .

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Editors and Affiliations

  1. c/o Editorial Board 978-0-387-78665 , Heidelberg, Baden-Württemberg, Germany

    Vinood Patel

  2. Kings College , London, United Kingdom

    Victor Preedy

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Albuquerque, D., Manco, L., Nóbrega, C. (2017). Molecular Biology of Human Obesity: Non-epigenetics in Comparison with Epigenetic Processes. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-31143-2_7-1

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  • DOI: https://doi.org/10.1007/978-3-319-31143-2_7-1

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