Genetics of human obesity: lessons from mouse models and candidate genes

Echwald, Søren M.

doi:10.1046/j.1365-2796.1999.00494.x

Cited by 25 publications

(16 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…82 Plasma leptin levels correlate with the degree of insulin resistance 79,80 with one study finding this occurs only in women. 83 In the current study, leptin levels were significantly higher in women compared with men, and for both sexes were positively correlated with both BMI and the well-studied marker of inflammation CRP.…”

Section: Discussionsupporting

confidence: 52%

Risk indicators of metabolic syndrome in young adults: A preliminary investigation on the influence of tobacco smoke exposure and gender

et al. 2006

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 52%

Risk indicators of metabolic syndrome in young adults: A preliminary investigation on the influence of tobacco smoke exposure and gender

et al. 2006

View full text Add to dashboard Cite

“…Phenotypic expressions are much more limited than the links in the chain of regulation, therefore nature selects for different genes with the same phenotypic result. In case of obesity, it is likely that the genetic component may explain a large part of the variability of BMI, and that up to 80% of the tendency to obesity has a genetic basis [83]. Our genome has literally hundreds of markers linked to obesity; the loci have been identified on all (except Y) chromosomes and on almost all of them there is more than one locus.…”

Section: Evolutionary Aspects Of Fat Accumulationmentioning

confidence: 99%

Human obesity: an evolutionary approach to understanding our bulging waistline

Lev-Ran

2001

Diabetes Metabolism Res

130

View full text Add to dashboard Cite

The unique worldwide spread of the human species and the remarkably long post-reproductive survival show that our genome permits excellent adaptation to vastly different environments. Moreover, the main scourges of later age, namely malignant growths and atherosclerosis, appear in humans later than in shorter-living animals. In recent years, excess weight and obesity have become mass phenomena with a pronounced upward trend in all developed countries. However, despite the detrimental effects of being overweight, these populations live longer than ever, which in part may be explained by the availability of better medical treatment. The prevalence and predicted further spread of obesity can be understood in the light of evolution. In all animal species energy metabolism is asymmetric with energy accumulation ('thrifty genotype') being the necessary condition of survival during hard times. For humans, which are no different to other animals in this respect, this genetic programming was necessary for survival because during the course of history, including the recorded history in the more developed Middle East, Europe or China, there was never a long period of uninterrupted food abundance, whereas famines were regular and frequent. Therefore fat accumulation, when food was available, meant survival at times of shortage, while the possible detrimental effects of overindulgence in food and being overweight expressed in unrealistically old age were irrelevant. It is the central, mostly intra-abdominal fat (in both humans and animals) that is more medically important than the subcutaneous truncal fat, and the accumulation of both types of fat is conditioned by high food consumption; therefore it is a historic novelty for human populations. In contrast, lower-body fat in human females is unique in the animal kingdom: it is much less metabolically active, it is of much lower pathologic significance than central fat, and it is programmed to be mobilized mostly during pregnancy and lactation. In view of all this, norms of desired weight should be based on hard mortality and morbidity statistics and not on theoretical, esthetic or fashion considerations. By this criterion, the upper limit of desirable weight is likely to be body mass index (BMI) 27 or 28, but specified for different populations (sex, race, ethnic origin); moreover, with aging, the detrimental effects of obesity diminish and finally disappear. Risks of other pathologies related to obesity (e.g. diabetes, hypertension and coronary disease) are also population-specific. However, total fatness, measured by BMI, is insufficiently sensitive as a risk factor, and fat distribution (upper-body versus low-body type, as reflected by waist circumference and waist:hip ratio) plays at least as prominent a role. Therefore the detailed norms, not yet available, should take into account both general obesity and fat distribution and be specific for different populations. Since long-term weight loss in adults is rarely achievable, public health measures should be aggressively d...

show abstract

“…Four isoforms have been found in humans: a long isoform, and three shorter isoforms generated by alternative splicing from a single gene locus on chromosome 1 p. 7 Mouse studies have shown that a mutation in the LEPR gene of dbadb mice leads to abnormal mRNA splicing, giving abnormal signal transduction, complete leptin resistance and obesity. 8,9 It was therefore postulated that defects in the LEPR gene might contribute to obesity in humans. 1 A common variant in exon 6 of LEPR, which causes an amino acid change, Gln223Arg (located in the extracellular domain), and has been associated with variation in BMI, fat mass and fat-free mass in middle aged Caucasian males.…”

Section: Introductionmentioning

confidence: 99%

Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in UK and South Asian populations

et al. 2001

View full text Add to dashboard Cite

BACKGROUND:Leptin is an adipocyte secreted hormone involved in regulation of body weight and metabolism in man. Placenta leptin levels correlate positively with birth weight. It is therefore possible that variation in the leptin receptor gene (LEPR) may contribute to obesity and in¯uence birth weight. OBJECTIVE: This study investigates the in¯uence of the leptin receptor gene variant Gln223Arg (A?G, 668), on maternal body mass index (BMI), foetal gestational length and birth weight in a cohort of 455 healthy pregnant women of Asian Indian (India, Bangladesh, Pakistan) and UKaIrish origin. RESULTS: Maternal genotype distributions did not differ from those expected under Hardy ± Weinberg equilibrium conditions in either population of origin. Maternal genotype for the Gln223Arg leptin receptor gene polymorphism showed no signi®cant association with foetal birth weight (adjusted for gestational length) or with maternal BMI during ®rst trimester (adjusted for age) in either population group. CONCLUSION: These results suggest that the Gln223Arg variant in the maternal leptin receptor gene does not explain the association between placental leptin levels and birth weight, and is not associated with variation in maternal BMI in early pregnancy in our sample.

show abstract

Genetics of human obesity: lessons from mouse models and candidate genes

Cited by 25 publications

References 109 publications

Risk indicators of metabolic syndrome in young adults: A preliminary investigation on the influence of tobacco smoke exposure and gender

Risk indicators of metabolic syndrome in young adults: A preliminary investigation on the influence of tobacco smoke exposure and gender

Human obesity: an evolutionary approach to understanding our bulging waistline

Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in UK and South Asian populations

Contact Info

Product

Resources

About