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Molecular Biology of Human Obesity: Nonepigenetics in Comparison with Epigenetic Processes

  • David AlbuquerqueEmail author
  • Licínio Manco
  • Clévio Nóbrega
Reference work entry

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.

Keywords

Obesity Genetic of obesity Mutations Genome-wide association study (GWAS) Energy homeostasis Leptin/melanocortin pathway Single-nucleotide polymorphism (SNP) Heritability Copy number variation (CNV) DNA methylation Histone modification MicroRNA Fetal programming 

List of 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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • David Albuquerque
    • 1
    Email author
  • Licínio Manco
    • 1
  • Clévio Nóbrega
    • 2
    • 3
  1. 1.Department of Life Sciences, Research Centre for Anthropology and Health (CIAS)University of CoimbraCoimbraPortugal
  2. 2.Department of Biomedical Sciences and Medicine, Center for Biomedical Research (CBMR)University of AlgarveFaroPortugal
  3. 3.Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal

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