Biallelic and triallelic approaches of 5-HTTLPR polymorphism are associated with food intake and nutritional status in childhood

Miranda, Raquel; Genro, Júlia Pasqualini; Campagnolo, Paula Dal Bó; Mattevi, Vanessa Suñé; Vítolo, Márcia Regina; Almeida, Silvana

doi:10.1016/j.jnutbio.2017.01.015

Cited by 6 publications

(9 citation statements)

References 39 publications

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“… 40 With regards to obesity, SLC6A4 is the most frequently assessed gene within the 5‐HT systems. Several genetic variations mapped to this gene have been examined, which include an insertion/deletion variant within the 5‐HT transporter linked polymorphic region (5‐HTTLPR), 8 , 9 , 11 , 12 , 13 and a 17‐bp variable number of tandem repeats sequence in the second intron (Stin2). 8 , 10 , 13 5‐HTTLPR was assessed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…To date, the most frequently assessed genetic variations within the 5‐HT systems related to obesity are located at the SLC6A4 gene, although findings are not consistent. 8 , 9 , 10 , 11 , 12 , 13 , 14 Variations in SLC6A4 have also been linked with obesogenic eating behaviors, such as appetite, energy intake, disinhibited eating, and emotional eating. 9 , 15 , 16 , 17 In addition to SLC6A4 , several 5‐HT receptor genes and TPHs, including HTR1B , 18 , 19 HTR2A , 20 , 21 , 22 , 23 HTR2B , 24 HTR2C , 11 , 18 , 20 , 25 , 26 , 27 HTR6 , 28 HTR7 , 19 TPH1 , and TPH2 24 , 29 have also been assessed for potential associations with body weight measures and/or eating behaviors.…”

Section: Introductionmentioning

confidence: 99%

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Serotonin system genes contribute to the susceptibility to obesity in Black adolescents

Meng

Groth

Hodgkinson

et al. 2021

Obesity Science & Practice

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Objective The importance of the central and peripheral serotonin systems in regulating energy balance and obesity development has been highlighted in animal models. Yet, the role of both serotonin systems has not been systematically assessed in humans. The purpose of this study was to investigate the association of genes within both serotonin systems with obesity outcomes in black adolescents. Methods African–American adolescents (n = 1052) whose mothers participated the Memphis New Mother's Study were assessed. In total, 110 polymorphisms mapped to 10 serotonin genes were examined for their associations with standardized body mass index (BMI‐z) scores and waist circumferences using generalized estimating equation models. Results Over 39% of adolescents were overweight or had obesity. Three single nucleotide polymorphisms (SNPs) within TPH2, HTR3B, and SLC6A4, were significantly associated with BMI‐z scores (p < 1.7 × 10−3). Two SNPs in TPH2 were nominally associated with waist circumferences. One SNP in HTR2C was associated with BMI‐z scores (p = 0.001) and waist circumferences (p = 0.005) only in girls. Tissue‐specific expression indicates that three identified genes are predominantly expressed in the brain. Conclusion The central serotonin system may play a key role in obesity development in black adolescents. Future studies are warranted to explore additional serotonin system genes and their potential obesogenic mechanisms in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serotonin system genes contribute to the susceptibility to obesity in Black adolescents

Meng

Groth

Hodgkinson

et al. 2021

Obesity Science & Practice

View full text Add to dashboard Cite

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“…Furthermore, Lan et al described an age-dependent modification of 5-HTTLPR association with obesity development; they demonstrated that the SS genotype was associated with BMI and obesity in nonelderly patients with stroke but not in elderly patients [108]. Recently, it was found that Brazilian children with SS homozygotes also had higher anthropometric parameters (BMI Z -score, sum of skinfolds, and WC) and higher food intake at the assessments of the three stages in early childhood [109]. The S allele was also strongly associated with the presence of T2D in Greeks independent of obesity status [110], but no association with T2D and obesity was found in the Pakistani population [111].…”

Section: Main Textmentioning

confidence: 99%

The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications

Say

2017

J Physiol Anthropol

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BackgroundDespite the fact that insertions/deletions (INDELs) are the second most common type of genetic variations and variable number tandem repeats (VNTRs) represent a large portion of the human genome, they have received far less attention than single nucleotide polymorphisms (SNPs) and larger forms of structural variation like copy number variations (CNVs), especially in genome-wide association studies (GWAS) of complex diseases like polygenic obesity. This is exemplified by the vast amount of review papers on the role of SNPs and CNVs in obesity, its related traits (like anthropometric measurements, biochemical variables, and eating behavior), and its related complications (like hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance—collectively known as metabolic syndrome). Hence, this paper reviews the types of INDELs and VNTRs that have been studied for association with obesity and its related traits and complications.Main body of the abstractThese INDELs and VNTRs could be found in the obesity loci or genes from the earliest GWAS and candidate gene association studies, like FTO, genes in the leptin–proopiomelanocortin pathway, and UCP2/3. Given the important role of the brain serotonergic and dopaminergic reward system in obesity susceptibility, the association of INDELs and VNTRs in these neurotransmitters’ metabolism and transport genes with obesity is also reviewed. Next, the role of INS VNTR in obesity and its related traits is questionable, since recent large-scale studies failed to replicate the earlier positive associations. As obesity results in chronic low-grade inflammation of the adipose tissue, the proinflammatory cytokine gene IL1RA and anti-inflammatory cytokine gene IL4 have VNTRs that are implicated in obesity. A systemic proinflammatory state in combination with activation of the renin–angiotensin system and decreased nitric oxide bioavailability as found in obesity leads to endothelial dysfunction. This explains why VNTR and INDEL in eNOS and ACE, respectively, could be predisposing factors of obesity. Finally, two novel genes, DOCK5 and PER3, which are involved in the regulation of the Akt/MAPK pathway and circadian rhythm, respectively, have VNTRs and INDEL that might be associated with obesity.Short conclusionIn conclusion, INDELs and VNTRs could have important functional consequences in the pathophysiology of obesity, and research on them should be continued to facilitate obesity prediction, prevention, and treatment.

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“…A selective serotonin reuptake inhibitor blunts the standard appetite-related responses to highly palatable or aversive tastants ( Mathes et al, 2013 ). Additionally, the 5-HT system has been implicated in emotional eating in humans, polymorphisms within serotonin transporter linked polymorphic region (5-HTTLPR) are associated with stress-induced eating susceptibility ( Chen et al, 2015 ) and obesity in childhood ( Miranda et al, 2017 ), adolescence ( Sookoian et al, 2007 ) and adulthood ( Fuemmeler et al, 2008 ). Together these data demonstrate a relationship between serotonin signalling within the brain, and diet-induced obesity.…”

Section: Introductionmentioning

confidence: 99%

Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice

Beecher

Wang

Jacques

et al. 2021

Front. Mol. Neurosci.

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The overconsumption of sugar-sweetened food and beverages underpins the current rise in obesity rates. Sugar overconsumption induces maladaptive neuroplasticity to decrease dietary control. Although serotonin and glutamate co-localisation has been implicated in reward processing, it is still unknown how chronic sucrose consumption changes this transmission in regions associated with executive control over feeding—such as the prefrontal cortex (PFC) and dentate gyrus (DG) of the hippocampus. To address this, a total of 16 C57Bl6 mice received either 5% w/v sucrose or water as a control for 12 weeks using the Drinking-In-The-Dark paradigm (n = 8 mice per group). We then examined the effects of chronic sucrose consumption on the immunological distribution of serotonin (5-HT), vesicular glutamate transporter 3 (VGLUT3) and 5-HT+/VGLUT3+ co-localised axonal varicosities. Sucrose consumption over 12 weeks decreased the number of 5-HT–/VGLUT3+ and 5-HT+/VGLUT3+ varicosities within the PFC and DG. The number of 5-HT+/VGLUT3– varicosities remained unchanged within the PFC but decreased in the DG following sucrose consumption. Given that serotonin mediates DG neurogenesis through microglial migration, the number of microglia within the DG was also assessed in both experimental groups. Sucrose consumption decreased the number of DG microglia. Although the DG and PFC are associated with executive control over rewarding activities and emotional memory formation, we did not detect a subsequent change in DG neurogenesis or anxiety-like behaviour or depressive-like behaviour. Overall, these findings suggest that the chronic consumption of sugar alters serotonergic neuroplasticity within neural circuits responsible for feeding control. Although these alterations alone were not sufficient to induce changes in neurogenesis or behaviour, it is proposed that the sucrose consumption may predispose individuals to these cognitive deficits which ultimately promote further sugar intake.

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Biallelic and triallelic approaches of 5-HTTLPR polymorphism are associated with food intake and nutritional status in childhood

Cited by 6 publications

References 39 publications

Serotonin system genes contribute to the susceptibility to obesity in Black adolescents

Serotonin system genes contribute to the susceptibility to obesity in Black adolescents

The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications

Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice

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