Role of ADHD symptoms as a contributing factor to obesity in patients with MC4R mutations

Porfirio, Maria Cristina; Giovinazzo, Silvia; Cortese, Samuele; Giana, G.; Lo-Castro, Adriana; Mouren, Marie Christine; Curatolo, Paolo; Purper-Ouakil, Diane

doi:10.1016/j.mehy.2014.11.004

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…In addition to early-onset obesity, a higher prevalence of ADHD has been reported in MC4R mutation carriers [42]. It has been hypothesized that such co-occurrence may be, in part, underpinned by reward processing deficits [43], and animal studies provide further support regarding the involvement of MC4R signaling and dopaminergic-dependent reward processing [41].…”

Section: Discussionmentioning

confidence: 99%

Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

Mota

Poelmans

Klein

et al. 2020

Neuropsychopharmacol.

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Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD-BMI overlapping genes with brain volumes (primary GWAS data N = 10,720-10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10 −3) and BMI (P = 1.63 × 10 −5); the circadian rhythm was associated with BMI (P = 1.28 × 10 −3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD-BMI and ADHD-obesity results. The ADHD-BMI overlapping genes were associated with putamen volume (P = 7.7 × 10 −3 ; replication data P = 3.9 × 10 −2)-a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.

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Section: Discussionmentioning

confidence: 99%

Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

Mota

Poelmans

Klein

et al. 2020

Neuropsychopharmacol.

View full text Add to dashboard Cite

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“…ADHD-like symptoms observed in ~80% of homozygous carriers of MC4R mutations, resulting in severe obesity, suggests the possibility of reverse causality or shared pathways 25 . An informative approach to exploring the causal relationship between risk-taking and BMI is Mendelian randomisation (MR) using genetic variants associated with risk-taking as instrumental variables.…”

Section: Introductionmentioning

confidence: 99%

Genome–wide association study for risk taking propensity indicates shared pathways with body mass index

et al. 2018

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Risk-taking propensity is a trait of significant public health relevance but few specific genetic factors are known. Here we perform a genome-wide association study of self-reported risk-taking propensity among 436,236 white European UK Biobank study participants. We identify genome-wide associations at 26 loci (P < 5 × 10−8), 24 of which are novel, implicating genes enriched in the GABA and GABA receptor pathways. Modelling the relationship between risk-taking propensity and body mass index (BMI) using Mendelian randomisation shows a positive association (0.25 approximate SDs of BMI (SE: 0.06); P = 6.7 × 10−5). The impact of individual SNPs is heterogeneous, indicating a complex relationship arising from multiple shared pathways. We identify positive genetic correlations between risk-taking and waist-hip ratio, childhood obesity, ever smoking, attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia, alongside a negative correlation with women’s age at first birth. These findings highlight that behavioural pathways involved in risk-taking propensity may play a role in obesity, smoking and psychiatric disorders.

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“…USC can be expanded to generate more than a million donor specific cells by two consecutive subcultures after their in-vitro isolation. The second type, so called “renal epithelial cells” or “renal cells” are considered less potent than USC in terms of gene expression and in-vitro expandability [ 4 ]. Compared with the renal cells, USC can generate more donor-specific multipotent cells by cell culture.…”

Section: Isolation Of Urine-derived Cellsmentioning

confidence: 99%

“…Urine cells can be isolated using a relatively simple method and be expanded easily. In addition, the possibility of generating cells from urine samples makes the human urine-derived cells an attractive alternative choice for cell therapy [ 3 , 4 ]. However, few manuscripts have been published thus far to describe the use of these cells in cell therapy.…”

Section: Introductionmentioning

confidence: 99%

Urine-derived cells for human cell therapy

et al. 2018

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Desirable cells for human cell therapy would be ones that can be generated by simple isolation and culture techniques using a donor sample obtained by non-invasive methods. To date, the different donor-specific cells that can be isolated from blood, skin, and hair require invasive methods for sample isolation and incorporate complex and costly reagents to culture. These cells also take considerable time for their in-vitro isolation and expansion. Previous studies suggest that donor-derived cells, namely urine stem cells and renal cells, may be isolated from human urine samples using a cost-effective and simple method of isolation, incorporating not such complex reagents. Moreover, the isolated cells, particularly urine stem cells, are superior to conventional stem cell sources in terms of favourable gene profile and inherent multipotent potential. Transdifferentiation or differentiation of human urine-derived cells can generate desirable cells for regenerative therapy. In this review, we intended to discuss the characteristics and therapeutic applications of urine-derived cells for human cell therapy. Conclusively, with detailed study and optimisation, urine-derived cells have a prospective future to generate functional lineage-specific cells for patients from a clinical translation point of view.

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Role of ADHD symptoms as a contributing factor to obesity in patients with MC4R mutations

Cited by 11 publications

References 27 publications

Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

Genome–wide association study for risk taking propensity indicates shared pathways with body mass index

Urine-derived cells for human cell therapy

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