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Review
. 2007 Aug;23 Suppl A(Suppl A):23A-27A.
doi: 10.1016/s0828-282x(07)71002-4.

Genetic contributors to obesity

Ruth McPherson  1
Affiliations
Review

Genetic contributors to obesity

Ruth McPherson. Can J Cardiol. 2007 Aug.

Abstract
in English, French

Genetic and environmental factors interact to regulate body weight. Overall, the heritability of obesity is estimated at 40% to 70%. More than 244 genes have been found to strongly affect adiposity when overexpressed or deleted in mice. These genes can be considered in four broad categories: regulation of food intake by molecular signalling in the hypothalamus and hindbrain by signals originating in adipose tissue, gut and other organs; regulation of adipocyte differentiation and fat storage; regulation of spontaneous exercise activity; and effect on basal and postprandial thermogenesis. Rare variants in the coding sequences of major candidate genes account for an obese phenotype in 5% to 10% of individuals.

Les facteurs génétiques et environnementaux interagissent pour réguler le poids corporel. Dans l’ensemble, on estime l’héritabilité de l’obésité à entre 40 % et 70 %. On a découvert que plus de 244 gènes ont un effet important sur l’adiposité lorsqu’ils sont surexprimés et ou supprimés chez les souris. Ces gènes peuvent être divisés entre quatre grandes catégories : la régulation de l’apport alimentaire par la signalisation moléculaire dans l’hypothalamus et le rhombencéphale au moyen de signaux en provenance des tissus adipeux, de l’estomac et d’autres organes, la régulation de la différenciation adipeuse et du stockage de gras, la régulation de l’activité physique spontanée et l’effet de la thermogenèse basale et postprandiale. De rares variantes des séquences de codage des principaux gènes candidats représentent un phénotype d’obésité chez 5 % à 10 % des individus.

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Figures

Figure 1)
Figure 1)
Early insights into the genetic etiology of obesity. Reproduced from reference
Figure 2)
Figure 2)
Regulation of energy balance. Overall, genes that may contribute to obesity susceptibility can be considered in four broad areas. These include genes that regulate food intake, participate in adipogenesis and triglyceride storage, affect spontaneous activity, and influence basal and postprandial energy expenditure via effects on mitochondrial proton leak and adaptive thermogenesis
Figure 3)
Figure 3)
Hypothalamic regulation of food intake. The arcuate nucleus of the hypothalamus comprises two sets of neurons with opposing effects on food intake and energy balance. Activation of the agouti-related peptide (AgRP) and neuropeptide Y (NPY) neurons increases food intake, whereas activation of the proopiomelanocortin (POMC) and cocaine-and amphetamine-related transcript neurons results in the release of alpha-melanocyte-stimulating hormone (αMSH), which binds to the melanocortin-4 receptor (MC4R) in the paraventricular nucleus to both inhibit food intake and increase energy expenditure. Leptin production by fat cells is proportional to fat cell mass. Leptin signals in the arcuate nucleus of the hypothalamus to downregulate (−) the orexigenic NPY and AgRP neurons, and to upregulate (+) the appetite-suppressing POMC neurons
See this image and copyright information in PMC

References

    1. Bodurtha JN, Mosteller M, Hewitt JK, et al. Genetic analysis of anthropometric measures in 11-year-old twins: The Medical College of Virginia Twin Study. Pediatr Res. 1990;28:1–4. - PubMed
    1. MacDonald A, Stunkard A. Body-mass indexes of British separated twins. N Engl J Med. 1990;322:1530. - PubMed
    1. Stunkard AJ, Sorensen TI, Hanis C, et al. An adoption study of human obesity. N Engl J Med. 1986;314:193–8. - PubMed
    1. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins who have been reared apart. N Engl J Med. 1990;322:1483–7. - PubMed
    1. Rankinen T, Zuberi A, Chagnon YC, et al. The human obesity gene map: The 2005 update. Obesity (Silver Spring) 2006;14:529–644. - PubMed