Genetic approaches to understanding human obesity

Ramachandrappa, Shwetha; Farooqi, I. Sadaf

doi:10.1172/jci46044

Cited by 173 publications

(156 citation statements)

References 115 publications

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“…The positive and negative association, respectively, of leptin and adiponectin expression with fat mass is well known [52]. The variations on adipokines expression in mice fed the oilseed-supplemented diets followed this trend.…”

Section: Discussionmentioning

confidence: 64%

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

et al. 2014

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Purpose and background The focus was directed to the study of two of the most lignan-rich food sources: sesame and flaxseeds. Recent epidemiological and experimental evidences suggesting that these foods may improve metabolic functions underlying metabolic syndrome (MetS). Methods To characterize the effect of these oilseeds on metabolic functions, we conducted an experimental study aimed at preventing adiposity and metabolic imbalance in a mouse model of high-fat diet (HFD)-induced MetS. Statistical analysis was performed by two-way analysis of variance test followed by post hoc Bonferroni analysis. Results We studied the effect of the oilseeds sesame and flaxseed on metabolic parameters in mice on a HFD. When the HFD was integrated with 20 % of sesame or flaxseed flours, the mice showed a decrease in body fat, already at day 15, from time 0. The size of the adipocytes was smaller in epididymal fat, liver steatosis was inhibited, and insulin sensitivity was higher in mice on the supplemented diets. The supplemented diets also resulted in a significant increase in the serum levels of the lignan metabolites enterodiol and enterolactone compared with the controls. The expression of genes associated with the inflammatory response, glucose metabolism, adipose metabolism and nuclear receptor were altered by the oilseed-supplemented diets. Some of the most abundant lignans in these oilseeds were studied in 3T3-L1 preadipocyte cells and were effective in inhibiting adipocyte differentiation at the minimal dose of 1 nM. Conclusions The consumption of sesame and flaxseed may be beneficial to decrease metabolic parameters that are generally altered in MetS.

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Section: Discussionmentioning

confidence: 64%

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

et al. 2014

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“…The GWAS proved to be powerful and efficient in the identification of genetic variants associated with complex diseases (Ramachandrappa and Farooqi 2011). Using many common variants, this case-control study approach screened the whole genome at much higher resolution than the approach previously described.…”

Section: Genome-wide Approachmentioning

confidence: 99%

Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective

et al. 2015

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Although the prevalence of obesity is increasing in most countries, partially due to ubiquitous exposure to energy dense foods, not everyone exposed to the current obesogenic environment shows unhealthy weight gain. This suggests that there are marked differences in genetic factors that increase vulnerability for excess weight gain. Indeed, evidence suggests that 40 to 70% of variance in unhealthy weight gain can be attributed to individual genetic variations. Moreover, emerging data imply that genetic vulnerability factors interact with environment risk, which is referred to as an epigenetic process.Whereas most scholars consider obesity to be a disorder that results from the interaction between lifestyle and genetic factors, its origin is complex, poorly understood, and extent treatments are typically ineffective. Like any other aspect of science, our knowledge about the genetic basis of obesity is under constant revision. The current paper provides a review on the origins, mechanisms, evolutionary explanation, prevention and treatment based on genotyping.

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“…After discarding other signals and/or symptoms to which obesity is related as a main part of more complex genetic disease, patients affected with nonsyndromic obesity who display a Mendelian pattern of inheritance, account for approximately 5% of all severe and early-onset obese cases (Bell et al, 2005). This group represents the most extreme obese phenotype, among which individuals carrying mutations in the melanocortin-4 receptor (MC4R) and/or leptin receptor (LEPR) genes become obese at a very young age, remaining severely obese into adulthood (Ramachandrappa & Farooqi, 2011). Most of these mutations result from disruption of the leptin/melanocortin pathway in the central nervous system, which is critical in the regulation of energy balance (Coll et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Most of these mutations result from disruption of the leptin/melanocortin pathway in the central nervous system, which is critical in the regulation of energy balance (Coll et al, 2004). Until now, approximately 20 genes have been implicated in nonsyndromic forms of monogenic obesity (Ramachandrappa & Farooqi, 2011;El-Sayed Moustafa & Froguel, 2013).…”

Section: Introductionmentioning

confidence: 99%

Novel Variants in theMC4RandLEPRGenes among Severely Obese Children from the Iberian Population

Albuquerque

Estévez

Beato-Víbora

et al. 2014

Annals of Human Genetics

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SummaryWe screened for mutations in the MC4R and LEPR genes and investigated the genotype-phenotype correlation in obese individuals belonging to families with evident hereditary patterns of severe and early-onset obesity among the Iberian population.A total of 202 unrelated and severely obese patients since childhood, were enrolled in the study. Bidirectional sequencing of the MC4R gene was carried out in all patients; the LEPR gene was sequenced in 15 individuals based on additional clinical signals. Segregation analysis and/or genotype-phenotype description was performed for subjects with the new mutations and with presumably functional variants.

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Genetic approaches to understanding human obesity

Cited by 173 publications

References 115 publications

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective

Novel Variants in theMC4RandLEPRGenes among Severely Obese Children from the Iberian Population

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