Search results for "melanocortin"

The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

2019

International audience; Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-l…

2018

OBJECTIVE The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. METHODS We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from …

Human POMC processing in vitro and in vivo revealed by quantitative peptidomics

2018

ABSTRACTHuman obesity can result from the aberrant production or processing of proopiomelanocortin (POMC) in hypothalamic neurons, but it is unclear which human POMC-derived peptides are most relevant to body weight regulation. To address this question, we analysed both hypothalamic neurons derived from human pluripotent stem cells (hPSCs) and primary human hypothalamic tissue using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS). In both in vitro- and in vivo-derived samples, we found that POMC was processed into β-melanocyte stimulating hormone (β-MSH), whose existence in the human brain has been controversial. β-MSH and desacetyl α-MSH (d-α-MSH) were produced at ro…

A melanocortin 1 receptor (MC1R) gene polymorphism is useful for authentication of Massese sheep dairy products

2011

Massese is an Italian sheep breed, with black or grey coat colour, mainly reared in the Tuscany and Emilia Romagna regions. Recently, the emerging interests in this breed have resulted in the production of Pecorino cheese obtained with only Massese milk. In order to be profitable, this marketing link between Massese breed and its products should be defended against fraudsters who could include milk of other sheep breeds or cow milk in Massese labelled productions. To identify the genetic factors affecting coat colour in sheep, we have recently analysed the melanocortin 1 receptor (MC1R) gene and identified several single nucleotide polymorphisms (SNPs). In this work, as a first step to set …

Genetic screening for MC4R gene identifies three novel mutations associated with severe familiar obesity in a cohort of Spanish individuals

2019

Abstract MC4R gene is a hypothalamic satiety control mediator in which mutations cause a monogenic form of obesity. The aim of this study was to perform a genetic screening to identify variations in the entire region of MC4R gene. A total of 236 unrelated and severely obese patients (BMI ≥ 40 kg/m2) with Spanish ancestry and severe overweight familiar history have been enrolled into the study. Seven MC4R gene variants were identified in the heterozygous state in 21 patients. Coding variants p.Thr101Ile and p.Ala259Asp are new and variants p.Ser30Phe, p.Val103Ile and p.Ile251Leu were previously described. Two variants have been also observed in the promoter region of the MC4R gene; the c.-24…

Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice

2021

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight …

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to th…

2012

Background: Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Methods: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes c…

The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model

2006

Melanocortins possess strong anti-inflammatory effects acting in the central nervous system via inhibition of the production of nitric oxide (NO) during brain inflammation. To shed more light into the role of melanocortin (MC) receptor subtypes involved we synthesized and evaluated some novel peptides, modified in the melanocyte-stimulating hormone (MSH) core structure, natural MCs and known MC receptor selective peptides - MS05, MS06. Since the study included both selective, high affinity binders and the novel peptides, it was possible to do the correlation analysis of binding activities and the NO induction-related anti-inflammatory effect of the peptides. beta-MSH, gamma1-MSH, gamma2-MSH…

Single administration of tripeptide α-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain inj…

2013

Following traumatic brain injury (TBI) neuroinflammatory processes promote neuronal cell loss. Alpha-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with immunomodulatory properties, which may offer neuroprotection. Due to short half-life and pigmentary side-effects of α-MSH, the C-terminal tripeptide α-MSH(11-13) may be an anti-inflammatory alternative. The present study investigated the mRNA concentrations of the precursor hormone proopiomelanocortin (POMC) and of melanocortin receptors 1 and 4 (MC1R/MC4R) in naive mice and 15 min, 6, 12, 24, and 48 h after controlled cortical impact (CCI). Regulation of POMC and MC4R expression did not change after trauma, while MC1R levels incr…

Betulin binds to melanocortin receptors and antagonizes alpha-melanocyte stimulating hormone induced cAMP generation in mouse melanoma cells.

2007

Betulin is a principal component of birch bark and is known to possess a broad range of biological activities, including antiinflammatory, antiviral and anticancer actions. The present study was carried out in vitro to clarify the influence of betulin on melanocortin (MC) receptor-ergic signalling by using COS-7 cells transfected with corresponding human MC receptor DNA. The results showed that betulin binds to the human melanocortin MC1, three to five receptors with selectivity to the MC1 subtype (K(i) value 1.022 +/- 0.115 microM). Betulin binds to the MC receptors with the following potency order-MC > MC3 > MC5 > MC4. Betulin itself does not stimulate cAMP generation, however, it slightl…