Cocaine- and amphetamine-regulated transcript (CART): A multifaceted neuropeptide

Ahmadian-Moghadam, Hamid; Sadat‐Shirazi, Mitra‐Sadat; Zarrindast, Mohammad‐Reza

doi:10.1016/j.peptides.2018.10.008

Cited by 48 publications

(34 citation statements)

References 262 publications

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“…So, nutrigenetics and nutrigenomics studies can provide an understanding of the intra and inter population phenotypic differences in the effect of obesity on metabolic risk factors [7]. Over the past decades, genome-wide association studies (GWAS) have identified the cocaine-and amphetamine-regulated transcript prepropeptide gene encoding cocaine-and amphetamine-regulated transcript (CART) protein as a neurotransmitter and hormone [8][9][10], located in the arcuate nucleus of the hypothalamus [11] and implicated in several physiological processes such as neurological disease, anxiety, stress, addiction, depression, endocrine function, specially feeding behavior, weight management and energy homeostasis [10][11][12]. CART prepropeptide gene located in chromosome 5q13-14 in coexistence of proopiomelanocortin (POMC) neurons [12], contains one exon and two introns [11] and produces short peptide fragments [10,13] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals

2020

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Background: Epidemiologic studies show that cocaine-and amphetamine-regulated transcript prepropeptide (CARTPT) gene polymorphism modifies diet-obesity relationships. However, the interaction between CARTPT gene polymorphism and diet quality indices have not been investigated yet. The current study was aimed to evaluate the interaction between major dietary indices including Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI)-2015 and CARTPT gene rs2239670 variants among apparently healthy obese Iranians. Methods:This cross-sectional study was carried out by employing 288 apparently healthy obese adults aged 20-50 years with a BMI of 30-40 kg/m 2 . Diet quality was evaluated by Diet Quality Index-International (DQI-I) and Healthy Eating Index-2015 (HEI-2015) using a 132-items semi-quantitative validated food frequency questionnaire. The CARTPT gene rs2239670 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Blood concentrations of glycemic markers, lipid profile, α-melanocyte stimulating hormone (MSH) and agouti-related peptide (AgRP) were also measured. ANCOVA multivariate interaction model was used to analyze gene-diet interactions.Results: The significant interactions were identified between CARTPT gene polymorphism and HEI, affecting BMR (P Interaction = 0.003), serum glucose (P Interaction = 0.009) and high density lipoprotein cholesterol HDL concentrations (P Interaction = 0.03) after adjusting for the effects of sex and age. Also we found gene-diet interaction between CARTPT genotypes and DQI-I in terms of fat mass (FM; P Interaction = 0.02), waist circumference (WC; P Interaction < 0.001), body mass index (BMI; P Interaction < 0.001), basal metabolic rate (BMR, P Interaction < 0.001), serum fasting glucose (P Interaction < 0.01) and AgRP (P Interaction = 0.05) in individuals even after adjusting for potential confounders. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article' Conclusion: Current study showed the effects of interaction between CARTPT genotype with adherence to HEI and DQI-I scores on obesity-related anthropometric and metabolic risk-factors.

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Section: Introductionmentioning

confidence: 99%

Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals

2020

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“…In light of the neurochemical heterogeneity of this region, with several populations characterized by their expression of CART, neuropeptide Y and other peptidergic markers (Campbell et al, 2017), TH-negative/RXFP3-positive neurons in the ARC may constitute one or more of these other populations. ARC CART neurons express leptin receptors (Kristensen et al, 1998), and trigger anorexigenic pathways and reduced food consumption (Ahmadian-Moghadam et al, 2018). It is therefore possible that RXFP3 may be expressed by ARC CART neurons, and that RXFP3-mediated inhibition of these neurons may contribute to the orexigenic actions of RXFP3.…”

Section: Discussionmentioning

confidence: 99%

Differential Level of RXFP3 Expression in Dopaminergic Neurons Within the Arcuate Nucleus, Dorsomedial Hypothalamus and Ventral Tegmental Area of RXFP3-Cre/tdTomato Mice

et al. 2021

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RXFP3 (relaxin-family peptide 3 receptor) is the cognate G-protein-coupled receptor for the neuropeptide, relaxin-3. RXFP3 is expressed widely throughout the brain, including the hypothalamus, where it has been shown to modulate feeding behavior and neuroendocrine activity in rodents. In order to better characterize its potential mechanisms of action, this study determined whether RXFP3 is expressed by dopaminergic neurons within the arcuate nucleus (ARC) and dorsomedial hypothalamus (DMH), in addition to the ventral tegmental area (VTA). Neurons that express RXFP3 were visualized in coronal brain sections from RXFP3-Cre/tdTomato mice, which express the tdTomato fluorophore within RXFP3-positive cells, and dopaminergic neurons in these areas were visualized by simultaneous immunohistochemical detection of tyrosine hydroxylase-immunoreactivity (TH-IR). Approximately 20% of ARC neurons containing TH-IR coexpressed tdTomato fluorescence, suggesting that RXFP3 can influence the dopamine pathway from the ARC to the pituitary gland that controls prolactin release. The ability of prolactin to reduce leptin sensitivity and increase food consumption therefore represents a potential mechanism by which RXFP3 activation influences feeding. A similar proportion of DMH neurons containing TH-IR expressed RXFP3-related tdTomato fluorescence, consistent with a possible RXFP3-mediated regulation of stress and neuroendocrine circuits. In contrast, RXFP3 was barely detected within the VTA. TdTomato signal was absent from the ARC and DMH in sections from Rosa26-tdTomato mice, suggesting that the cells identified in RXFP3-Cre/tdTomato mice expressed authentic RXFP3-related tdTomato fluorescence. Together, these findings identify potential hypothalamic mechanisms through which RXFP3 influences neuroendocrine control of metabolism, and further highlight the therapeutic potential of targeting RXFP3 in feeding-related disorders.

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“…However, genetic variation in the CART locus may effect on the expression of the CART peptide, which is related to hypothalamic anorectic and orexigenic neuropeptides [37]. Totally, it seems that CART peptides have an anorexigenic effect, although the mechanism of this function is not completely known [38].…”

Section: Discussionmentioning

confidence: 99%

The interaction between dietary Non-Enzymatic Antioxidant Capacity (NEAC) and variant of Cocaine and Amphetamine-Regulated Transcript Prepropeptide (CARTPT) 5q13-14 - rs2239670 locus on hypothalamic-pituitary axis hormones and metabolic risk factors in obese individuals

Khodarahmi

Farhangi

Niknam

2020

Preprint

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BackgroundEpidemiological studies have illustrated that polymorphisms of Cocaine and Amphetamine-Regulated Transcript Prepropeptide gene (CARTPT) may affect obesity outcomes. However, no study has investigated the CARTPT gene-diet interactions in term of antioxidant potential of diet. This study aimed to evaluate the interactions between CARTPT gene and dietary non-enzymatic antioxidant capacity on hypothalamic- pituitary axis hormones and cardio-metabolic risk factors. Method and MaterialIn the present cross-sectional study, 288 apparently healthy obese adults aged 20–50 years with a body mass index (BMI) of 30–40 kg/m2 completed the study. Dietary assessment was performed by food frequency questionnaire (FFQ) and antioxidant capacity of diet was estimated by calculating the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total radical trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC). The CARTPT rs2239670 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique.ResultsThere was a significant interaction between CARTPT rs2239670 and dietary ORAC on BMI (Pinteraction = 0.048) and fat mass percent (FM%) (Pinteraction = 0.008); in A allele carriers, higher adherence to the dietary ORAC was related to lower level of BMI and FM%. As well as, the significant interactions were observed between FRAP index and rs2239670 in relation to HOMA (P interaction = 0.049) and QUICKI (P interaction = 0.048). Moreover, there were significant interactions of rs2239670 with TRAP (Pinteraction = 0.029) and TEAC (Pinteraction = 0.034) on the serum glucose level; individuals with AG genotype were more respondent to higher intake of TRAP.ConclusionThe present study indicated the interactions between CARTPT genotypes and dietary NEAC on obesity and its-related metabolic parameters. Further studies are warranted to confirm our findings.

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Cocaine- and amphetamine-regulated transcript (CART): A multifaceted neuropeptide

Cited by 48 publications

References 262 publications

Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals

Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals

Differential Level of RXFP3 Expression in Dopaminergic Neurons Within the Arcuate Nucleus, Dorsomedial Hypothalamus and Ventral Tegmental Area of RXFP3-Cre/tdTomato Mice

The interaction between dietary Non-Enzymatic Antioxidant Capacity (NEAC) and variant of Cocaine and Amphetamine-Regulated Transcript Prepropeptide (CARTPT) 5q13-14 - rs2239670 locus on hypothalamic-pituitary axis hormones and metabolic risk factors in obese individuals

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