scholarly journals Changes of agouti-related protein in hypothalamus, placenta, and serum during pregnancy in the rat

2009 ◽  
Vol 202 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Dawid Szczepankiewicz ◽  
Ewa Pruszynska-Oszmalek ◽  
Przemyslaw Kaczmarek ◽  
Marek Skrzypski ◽  
Karolina Andralojc ◽  
...  
Keyword(s):  
Energy Balance ◽  
Mrna Level ◽  
Late Pregnancy ◽  
Negative Energy ◽  
Related Protein ◽  
Protein Levels ◽  
Agouti Protein ◽  
Its Gene ◽  
Arcuate Nuclei ◽  
Agouti Related Protein

Agouti-related protein (AGRP) is a homolog of the agouti protein and acts as an antagonist of peptides derived from propiomelanocortin through melanocortin receptors. This peptide is produced mainly in the hypothalamus, particularly during negative energy balance and influences increased food intake. In the hypothalamus, this peptide is co-expressed in arcuate nuclei with neuropeptide Y, another important peptide that regulates energy metabolisms. In our study, we analyzed changes in the Agrp mRNA level in the hypothalamus as well as mRNA and protein levels in placenta during different stages of rat pregnancy. We also investigated the AGRP level in the blood serum. In this study, we found the AGRP level in serum increased, while its gene expression in the hypothalamus increased only up to the 13th day of pregnancy, and decreased on the 18th day. This study demonstrates that AGRP is expressed during late pregnancy in placenta. Moreover, we found that AGRP expression is higher on the 18th than on the 13th day of pregnancy. Our results indicate that AGRP may play an important role during pregnancy in the mother's and, possibly, also in the fetus's energy balance.

scholarly journals Role of Agouti-Related Protein-Expressing Neurons in Lactation

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 544-550 ◽  
Author(s):  
Colin T. Phillips ◽  
Richard D. Palmiter
Keyword(s):  
Energy Balance ◽  
Mouse Model ◽  
Neuropeptide Y ◽  
Diphtheria Toxin ◽  
Negative Energy ◽  
Related Protein ◽  
Compensatory Mechanisms ◽  
Hypothalamic Neurons ◽  
Agouti Related Protein

Hypothalamic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY) are thought to be important for regulation of feeding, especially under conditions of negative energy balance. The expression of NPY and AgRP increases during lactation and may promote the hyperphagia that ensues. We explored the role of AgRP neurons in reproduction and lactation, using a mouse model in which AgRP-expressing neurons were selectively ablated by the action of diphtheria toxin. We show that ablation of AgRP neurons in neonatal mice does not interfere with pregnancy, parturition, or lactation, suggesting that early ablation allows compensatory mechanisms to become established. However, ablation of AgRP neurons after lactation commences results in rapid starvation, indicating that both basal feeding and lactation-induced hyperphagia become dependent on AgRP neurons in adulthood. We also show that constitutive inactivation of Npy and Agrp genes does not prevent pregnancy or lactation, nor does it protect lactating dams from diphtheria toxin-induced starvation.

Agouti-related protein in patients with acute and weight-restored anorexia nervosa

2011 ◽  
Vol 41 (10) ◽  
pp. 2183-2192 ◽  
Author(s):  
J. V. Merle ◽  
V. Haas ◽  
R. Burghardt ◽  
N. Döhler ◽  
N. Schneider ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Weight Gain ◽  
Negative Energy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Related Protein ◽  
The Central Nervous System ◽  
Plasma Leptin ◽  
Agouti Related Protein ◽  
Partial Weight

BackgroundAn imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain.MethodPlasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain.ResultsIn weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients.ConclusionsOur results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.

scholarly journals Peripherally administered [Nle4,d-Phe7]-α-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice

2004 ◽  
Vol 33 (3) ◽  
pp. 693-703 ◽  
Author(s):  
N Hoggard ◽  
D V Rayner ◽  
S L Johnston ◽  
J R Speakman
Keyword(s):  
Energy Balance ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Caloric Restriction ◽  
Blood Brain Barrier ◽  
Resting Metabolic Rate ◽  
Melanocortin Receptors ◽  
Related Protein ◽  
Melanocyte Stimulating Hormone ◽  
Agouti Related Protein

The melanocortin system coordinates the maintenance of energy balance via the regulation of both food intake and energy expenditure. Leptin, a key adipogenic hormone involved in the regulation of energy balance is thought to act by stimulating production, in the hypothalamic arcuate nucleus, of α-melanocyte stimulating hormone (αMSH), a potent agonist of MC3/4 melanocortin receptors located in the paraventricular nucleus of the hypothalamus. Additionally leptin inhibits release of agouti-related protein (AgRP), an MC4R antagonist. During periods of caloric restriction, weight loss is not sustained because compensatory mechanisms, such as reduced resting metabolic rate (RMR) are brought into play. Understanding how these compensatory systems operate may provide valuable targets for pharmaceutical therapies to support traditional dieting approaches. As circulating leptin is reduced during caloric restriction, it may mediate some of the observed compensatory responses. In addition to decreases in circulating leptin levels, circulating AgRP is increased during fasting in rodents while αMSH is decreased. As central administration of AgRP depresses metabolism, we hypothesised that the peripheral rise in AgRP might be involved in signalling the depression of RMR during food restriction. We hypothesised that changes in plasma AgRP and αMSH may coordinate the regulation of changes in energy expenditure acting through central MC4 melanocortin receptors via the sympathetic nervous system. We show here that acute peripherally administered AgRP at supra-physiological concentrations in both lean (C57BL/6) and obese leptin-deficient (ob/ob) mice does not depress RMR, possibly because it crosses the blood–brain barrier very slowly compared with other metabolites. However, in vitro AgRP can decrease leptin secretion, by approximately 40%, from adipocytes into culture medium and may via this axis have an effect on energy metabolism during prolonged caloric restriction. In contrast, peripheral [Nle4,d-Phe7]-α MSH produced a large and sustained increase in resting energy expenditure (0.15 ml O2/min; P <0.05) with a similar response in leptin-deficient ob/ob mice (0.27 ml O2/min) indicating that this effect is independent of the status of leptin production in the periphery. In both cases respiratory exchange ratio and the levels of energy expended on spontaneous physical activity were unaffected by the administration of peripheral [Nle4,d-Phe7]-α MSH. In conclusion, αMSH analogues that cross the blood–brain barrier may significantly augment dietary restriction strategies by sustaining elevated RMR.

scholarly journals Plasma Agouti-Related Protein Levels in Acromegaly and Effects of Surgical or Pegvisomant Therapy

2019 ◽  
Vol 104 (11) ◽  
pp. 5453-5461 ◽  
Author(s):  
Pamela U Freda ◽  
Carlos Reyes-Vidal ◽  
Zhezhen Jin ◽  
Mya Pugh ◽  
Sunil K Panigrahi ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Repeated Measure ◽  
Related Protein ◽  
Protein Levels ◽  
Treatment Data ◽  
Gh Receptor Antagonist ◽  
Measure Analysis ◽  
Repeated Measure Analysis ◽  
Active Acromegaly ◽  
Agouti Related Protein

Abstract Context GH activates agouti-related protein (AgRP) neurons, leading to orexigenic responses in mice. The relationship between serum GH and plasma AgRP, which has been shown to reflect hypothalamic AgRP, has not been evaluated in humans. Objective To test the hypothesis that central stimulatory actions of GH on hypothalamic AgRP could be reflected in plasma AgRP in acromegaly. Methods We studied 23 patients with active acromegaly before and for ≤2 years after surgical (n = 13) or GH receptor antagonist therapy with pegvisomant (n = 10), and 100 healthy subjects with morning fasting blood samples for AgRP, leptin, GH, and IGF-1 and anthropometric measurements. Results The plasma AgRP levels were higher in those with active acromegaly than in the matched healthy subjects [median, 100 pg/mL; interquartile range (IQR), 78 to 139 pg/mL vs median, 63 pg/mL; IQR, 58 to 67 pg/mL; P < 0.0001]. Plasma AgRP decreased from before to after surgery (median, 102 pg/mL; IQR, 82 to 124 pg/mL vs median, 63 pg/mL; IQR, 55.6 to 83 pg/mL; P = 0.0024) and from before to during pegvisomant therapy (median, 97 pg/mL; IQR, 77 to 175 pg/mL vs median, 63; IQR, 61 to 109 pg/mL; P = 0.006). The plasma AgRP level correlated with GH (r = 0.319; P = 0.011) and IGF-1 (r = 0.292; P = 0.002). In repeated measure analysis, AgRP was significantly associated with IGF-1. Conclusions Our data have provided evidence of a stimulatory effect of GH on plasma AgRP in humans. The levels were greater in active acromegaly and decreased in parallel with GH and IGF-1 decreases with acromegaly treatment. Data from mice suggest that AgRP may mediate some of the known effects of GH on energy metabolism. This warrants further study in patients with acromegaly and other populations.

scholarly journals Complex Regulation of Mammalian Target of Rapamycin Complex 1 in the Basomedial Hypothalamus by Leptin and Nutritional Status

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4541-4551 ◽  
Author(s):  
Eneida C. Villanueva ◽  
Heike Münzberg ◽  
Daniela Cota ◽  
Rebecca L. Leshan ◽  
Keely Kopp ◽  
...  
Keyword(s):  
Energy Balance ◽  
Neuronal Activity ◽  
Leptin Receptor ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Hypothalamic Nucleus ◽  
Related Protein ◽  
Leptin Deficiency ◽  
Mtorc1 Signaling ◽  
Agouti Related Protein

Abstract The medial basal hypothalamus, including the arcuate nucleus (ARC) and the ventromedial hypothalamic nucleus (VMH), integrates signals of energy status to modulate metabolism and energy balance. Leptin and feeding regulate the mammalian target of rapamycin complex 1 (mTORC1) in the hypothalamus, and hypothalamic mTORC1 contributes to the control of feeding and energy balance. To determine the mechanisms by which leptin modulates mTORC1 in specific hypothalamic neurons, we immunohistochemically assessed the mTORC1-dependent phosphorylation of ribosomal protein S6 (pS6). In addition to confirming the modulation of ARC mTORC1 activity by acute leptin treatment, this analysis revealed the robust activation of mTORC1-dependent ARC pS6 in response to fasting and leptin deficiency in leptin receptor-expressing Agouti-related protein neurons. In contrast, fasting and leptin deficiency suppress VMH mTORC1 signaling. The appropriate regulation of ARC mTORC1 by mutant leptin receptor isoforms correlated with their ability to suppress the activity of Agouti-related protein neurons, suggesting the potential stimulation of mTORC1 by the neuronal activity. Indeed, fasting- and leptin deficiency-induced pS6-immunoreactivity (IR) extensively colocalized with c-Fos-IR in ARC and VMH neurons. Furthermore, ghrelin, which activates orexigenic ARC neurons, increased ARC mTORC1 activity and induced colocalized pS6- and c-Fos-IR. Thus, neuronal activity promotes mTORC1/pS6 in response to signals of energy deficit. In contrast, insulin, which activates mTORC1 via the phosphatidylinositol 3-kinase pathway, increased ARC and VMH pS6-IR in the absence of neuronal activation. The regulation of mTORC1 in the basomedial hypothalamus thus varies by cell and stimulus type, as opposed to responding in a uniform manner to nutritional and hormonal perturbations.

scholarly journals Endogenous Melanocortin Antagonist in Fish: Structure, Brain Mapping, and Regulation by Fasting of the Goldfish Agouti-Related Protein Gene

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4552-4561 ◽  
Author(s):  
José Miguel Cerdá-Reverter ◽  
Richard Ector Peter
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Brain Mapping ◽  
Arcuate Nucleus ◽  
Mrna Levels ◽  
Central Administration ◽  
Related Protein ◽  
Melanocortin Peptides ◽  
Agouti Related Protein ◽  
Tuberal Nucleus

Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin. In mammals, central AGRP expression is restricted to the arcuate nucleus in which it plays a key role in the control of energy balance by antagonizing melanocortin effects at melanocortin 4 receptors. In goldfish, melanocortin 4 receptor is profusely expressed within the main brain areas for the control of energy balance, and central administration of agonist or antagonist analogs inhibits or stimulates food intake, respectively. Here we demonstrate that the goldfish genome has a homologous gene to mammalian AGRP. Detailed brain mapping by in situ hybridization shows that AGRP is exclusively expressed in the ventrobasal hypothalamic lateral tuberal nucleus, the teleostean homolog of the arcuate nucleus. Fasting up-regulates its mRNA levels in the lateral tuberal nucleus. In the periphery, AGRP is expressed in several tissues including ovary, muscle, and ventral skin, suggesting that AGRP might regulate peripheral actions of melanocortin peptides. The results provide the first evidence for an endogenous melanocortin antagonist in nontetrapod species and suggest that hypothalamic overexpression during fasting might regulate the inhibitory effects of melanocortin peptides on food intake in goldfish.

scholarly journals Regulation of adipose tissue leptin secretion by alpha-melanocyte-stimulating hormone and agouti-related protein: further evidence of an interaction between leptin and the melanocortin signalling system

2004 ◽  
Vol 32 (1) ◽  
pp. 145-153 ◽  
Author(s):  
N Hoggard ◽  
L Hunter ◽  
JS Duncan ◽  
DV Rayner
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Receptor Subtype ◽  
Related Protein ◽  
Melanocortin System ◽  
Rat Adipocytes ◽  
Melanocyte Stimulating Hormone ◽  
Agouti Related Protein ◽  
Stimulating Hormone

The central role of the melanocortin system in the regulation of energy balance has been studied in great detail. However, the functions of circulating melanocortins and the roles of their peripheral receptors remain to be elucidated. There is increasing evidence of a peripheral action of melanocortins in the regulation of leptin production by adipocytes. Here we investigate the interaction of alpha-melanocyte stimulating hormone (alpha-MSH) and agouti-related protein (AgRP) in the regulation of leptin secretion from cultured rat adipocytes and examine the changes in circulating alpha-MSH and AgRP in lean and obese rodents after hormonal and energetic challenge. Leptin secretion (measured by ELISA) and gene expression (by real-time quantitative PCR) of differentiated rat adipocytes cultured in vitro were inhibited by the administration of alpha-MSH (EC50=0.24 nM), and this effect was antagonised by antagonists of the melanocortin receptors MC4R and MC3R (AgRP and SHU9119). The presence of MC4R in rat adipocytes (RT-PCR and restriction digest) supports the involvement of this receptor subtype in this interaction. Leptin administered to ob/ob mice in turn increases the release of alpha-MSH into the circulation, suggesting a possible feedback loop between the site of alpha-MSH release and the release of leptin from the adipose tissue. However, the physiological significance of this putative feedback probably depends upon the underlying state of energy balance, since in the fasting state low plasma alpha-MSH is paralleled by low plasma leptin.

scholarly journals Association Between C1q/TNF-Related Protein-1 Levels in Human Plasma and Epicardial Adipose Tissues and Congestive Heart Failure

2017 ◽  
Vol 42 (5) ◽  
pp. 2130-2143 ◽  
Author(s):  
Ying Yang ◽  
Si Liu ◽  
Rong-Yi Zhang ◽  
Hui Luo ◽  
Ling Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Related Protein ◽  
Tissue Samples ◽  
Protein Levels ◽  
Mitogen Activated Protein

Background/Aims: C1q and tumour necrosis factor-related protein 1 (CTRP1) possesses anti-atherogenic and anti-inflammatory effects. This study investigated whether the CTRP1 levels in the plasma and epicardial adipose tissue (EAT) were associated with congestive heart failure (CHF) and to disclose possible molecular mechanisms. Methods: Plasma and tissue samples were obtained from subjects with or without CHF. Plasma levels of CTRP1 were measured by ELISA. The mRNA levels of CTRP1 and inflammatory cytokines were detected by RT-PCR. The protein levels of CTRP1, aldosterone synthase (CYP11B2) and mitogen-activated protein kinase were examined by Western blotting. Results: The levels of CTRP1 in the plasma and EAT were higher in the CHF patients than those in the controls. There were no differences in the CTRP1 levels in cardiomyocytes between the CHF group and the non-CHF group. An exploratory survival analysis showed that higher CTRP1 values at admission were associated with a worse prognosis after discharge. CTRP1 increased the IL-6 mRNA level in H295R cells. CTRP1 recruited ERK1/2 and Jak-2 for aldosterone release by modulating the CYP11B2 protein level, and brain natriuretic peptide repressed the CTRP1-induced aldosterone release through the JAK2-STAT3 signalling pathways. Conclusion: The CTRP1 levels in the plasma and EAT were increased in the CHF patients. CTRP1 is involved in the pathogenesis of CHF by modulating IL-6 levels and aldosterone release.

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