scholarly journals The regulation of phoenixin: A fascinating multidimensional peptide

2021 ◽  
Author(s):  
Emma K McIlwraith ◽  
Ningtong Zhang ◽  
Denise D Belsham
Keyword(s):  
Food Intake ◽  
Transcriptional Control ◽  
Therapeutic Potential ◽  
Physiological Role ◽  
Reproductive Hormones ◽  
Main Function ◽  
Negative Results ◽  
Gene And Protein Expression ◽  
Its Gene ◽  
Range Of Functions

Abstract The phoenixin (PNX) peptide is linked to the control of reproduction, food intake, stress and inflammation. However, little is known about what regulates its gene and protein expression, information that is critical to understand the physiological role of PNX. In this review, we summarize what is known about the transcriptional control of Pnx and its receptor Gpr173. A main function of PNX is as a positive regulator of the hypothalamic-pituitary-gonadal axis, but there is a lack of research on its control by reproductive hormones and peptides. PNX is also associated with food intake and its expression is linked to feeding status, fatty acids, and glucose. It is influenced by environmental and hormonal-induced stress. The regulation of Pnx in most contexts remains an enigma, in part due to conflicting and negative results. An extensive analysis of the response of the Pnx gene to factors related to reproduction, metabolism, stress and inflammation is required. Analysis of the Pnx promoter and epigenetic regulation must be considered to understand how this level of control contributes to its pleiotropic effects. PNX is now linked to a broad range of functions, but more research on its gene regulation is required to understand its place in overall physiology and therapeutic potential.

scholarly journals Chromatin-Directed Proteomics Identifies ZNF84 as a p53-Independent Regulator of p21 in Genotoxic Stress Response

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2115
Author(s):  
Anna Strzeszewska-Potyrała ◽  
Karolina Staniak ◽  
Joanna Czarnecka-Herok ◽  
Mahmoud-Reza Rafiee ◽  
Marcin Herok ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Genotoxic Stress ◽  
Vital Role ◽  
Dna Double Strand Breaks ◽  
Independent Manner ◽  
Strand Breaks ◽  
Knock Down ◽  
Proteomic Approach ◽  
Gene And Protein Expression ◽  
Transcriptomic Changes

The p21WAF1/Cip1 protein, encoded by CDKN1A, plays a vital role in senescence, and its transcriptional control by the tumour suppressor p53 is well-established. However, p21 can also be regulated in a p53-independent manner, by mechanisms that still remain less understood. We aimed to expand the knowledge about p53-independent senescence by looking for novel players involved in CDKN1A regulation. We used a chromatin-directed proteomic approach and identified ZNF84 as a novel regulator of p21 in various p53-deficient cell lines treated with cytostatic dose of doxorubicin. Knock-down of ZNF84, an as-yet un-characterized protein, inhibited p21 gene and protein expression in response to doxorubicin, it attenuated senescence and was associated with enhanced proliferation, indicating that ZNF84-deficiency can favor senescence bypass. ZNF84 deficiency was also associated with transcriptomic changes in genes governing various cancer-relevant processes e.g., mitosis. In cells with ZNF84 knock-down we discovered significantly lower level of H2AX Ser139 phosphorylation (γH2AX), which is triggered by DNA double strand breaks. Intriguingly, we observed a reverse correlation between the level of ZNF84 expression and survival rate of colon cancer patients. In conclusion, ZNF84, whose function was previously not recognized, was identified here as a critical p53-independent regulator of senescence, opening possibilities for its targeting in novel therapies of p53-null cancers.

Ghrelin Regulates Insulin Release and Glycemia: Physiological Role and Therapeutic Potential

2008 ◽  
Vol 4 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Toshihiko Yada ◽  
Katsuya Dezaki ◽  
Hideyuki Sone ◽  
Masaru Koizumi ◽  
Boldbaatar Damdindorj ◽  
...  
Keyword(s):  
Insulin Release ◽  
Therapeutic Potential ◽  
Physiological Role

scholarly journals GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility

2012 ◽  
Vol 303 (7) ◽  
pp. E853-E864 ◽  
Author(s):  
Xinfu Guan ◽  
Xuemei Shi ◽  
Xiaojie Li ◽  
Benny Chang ◽  
Yi Wang ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Feeding Behavior ◽  
Gastric Motility ◽  
Late Onset ◽  
Physiological Role ◽  
Immune Defense ◽  
Melanocortin Receptor ◽  
Melanocortin System ◽  
Dorsomedial Nucleus

Glucagon-like peptides (GLP-1/2) are cosecreted from endocrine L cells in the gut and preproglucagonergic neurons in the brain. Peripheral GLP-2 action is essential for maintaining intestinal homeostasis, improving absorption efficiency and blood flow, promoting immune defense, and producing efficacy in treatment of gastrointestinal diseases. However, it is unknown if CNS GLP-2 plays a physiological role in the control of energy homeostasis. Since GLP-1/2 are cotranslated from preproglucagongene and coproduced by prohormone convertase-1, it is challenging to knockout GLP-2 only. Instead, our laboratory has generated a Glp2r-floxed mouse line to dissect cell-specific GLP-2 receptor GLP-2R) action in the regulation of energy balance. Our objective was to determine if GLP-2R in the hypothalamus modulates feeding behavior and gastric emptying. We show that Glp2r mRNA and protein are highly expressed in the arcuate nucleus and dorsomedial nucleus of the mouse hypothalamus. Using the Cre-LoxP system, we generated mice that lack Glp2r expression in POMC neurons (KO; mainly in the hypothalamus). The KO mice showed hyperphagic behavior (such as increases in food intake and meal frequency), accelerated gastric emptying (assessed by [13C]octanoic acid breath test), and late-onset obesity, yet there was no decrease in basal metabolic rate. Infusion of GLP-2 (2.5 nmol into the 4th ventricle) suppressed food intake and gastric emptying, while GLP-2-mediated effects were abolished in the melanocortin receptor-4 (MC4R) KO mice. We conclude that Glp2r deletion in POMC neurons enhances feeding behavior and gastric motility, whereas icv GLP-2R activation suppresses food intake and gastric emptying through the MC4R signaling pathway. This study indicates that CNS GLP-2R plays a physiological role in the control of feeding behavior and gastric emptying and that this is mediated probably through the melanocortin system.

Secretin as a satiation whisperer with the potential to turn into an obesity-curbing knight

Endocrinology ◽  
2021 ◽  
Author(s):  
Katharina Schnabl ◽  
Yongguo Li ◽  
Mueez U-Din ◽  
Martin Klingenspor
Keyword(s):  
Bariatric Surgery ◽  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Weight Control ◽  
Therapeutic Potential ◽  
Physiological Mechanism ◽  
Gut Hormones ◽  
Metabolic Effects ◽  
Beneficial Effects

Abstract The obesity pandemic requires effective preventative and therapeutic intervention strategies. Successful and sustained obesity treatment is currently limited to bariatric surgery. Modulating the release of gut hormones is considered promising to mimic bariatric surgery with its beneficial effects on food intake, body weight and blood glucose levels. The gut peptide secretin was the first molecule to be termed a hormone; nevertheless, it only recently has been established as a legitimate anorexigenic peptide. In contrast to gut hormones that crosstalk with the brain either directly or by afferent neuronal projections, secretin mediates meal-associated brown fat thermogenesis to induce meal termination, thereby qualifying this physiological mechanism as an attractive, peripheral target for the treatment of obesity. In this perspective, it is of pivotal interest to deepen our yet superficial knowledge on the physiological roles of secretin as well as meal-associated thermogenesis in energy balance and body weight regulation. Of note, the emerging differences between meal-associated thermogenesis and cold-induced thermogenesis must be taken into account. In fact, there is no correlation between these two entities. In addition, the investigation of potential effects of secretin in hedonic-driven food intake, bariatric surgery as well as chronic treatment using suitable application strategies to overcome pharmacokinetic limitations will provide further insight into its potential to influence energy balance. The aim of this article is to review the facts on secretin’s metabolic effects, address prevailing gaps in our knowledge, and provide an overview on the opportunities and challenges of the therapeutic potential of secretin in body weight control.

TRPV4: physiological role and therapeutic potential in respiratory diseases

2014 ◽  
Vol 388 (4) ◽  
pp. 421-436 ◽  
Author(s):  
Neil M. Goldenberg ◽  
Krishnan Ravindran ◽  
Wolfgang M. Kuebler
Keyword(s):  
Respiratory Diseases ◽  
Therapeutic Potential ◽  
Physiological Role

scholarly journals The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication

2018 ◽  
Vol 107 (1) ◽  
pp. 91-104 ◽  
Author(s):  
Yuko Maejima ◽  
Shoko Yokota ◽  
Katsuhiko Nishimori ◽  
Kenju Shimomura
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Fat Mass ◽  
Physiological Role ◽  
Leptin Resistance ◽  
Neural Pathways ◽  
Feeding Regulation ◽  
Food Intake Regulation ◽  
Intake Regulation ◽  
The Brain

Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxytocin neurons in the paraventricular nucleus (PVN) receive neural projections from the arcuate nucleus (ARC), which is an important center for feeding regulation. On the other hand, these neurons in the PVN and supraoptic nucleus project to the ARC. PVN oxytocin neurons also project to the brain stem and the reward-related limbic system. In addition to this, oxytocin induces lipolysis and decreases fat mass. However, these effects in feeding and adipose tissue are known to be dependent on body weight (BW). Oxytocin treatment is more effective in food intake regulation and fat mass decline for individuals with leptin resistance and higher BW, but is known to be less effective in individuals with normal BW. In this review, we present in detail the recent findings on the physiological role of oxytocin in feeding regulation and the anorexigenic neural pathway of oxytocin neurons, as well as the advantage of oxytocin usage for anti-obesity treatment.

Food intake regulation in late pregnancy and early lactation

1999 ◽  
Vol 24 ◽  
pp. 37-54 ◽  
Author(s):  
K. L. Ingvartsen ◽  
N. C. Friggens ◽  
P. Faverdin
Keyword(s):  
Food Intake ◽  
Late Pregnancy ◽  
Reproductive Hormones ◽  
Early Lactation ◽  
Physical Constraints ◽  
Body Reserves ◽  
Food Intake Regulation ◽  
Periparturient Cows ◽  
Intake Regulation

AbstractThe dip in food intake, which starts in late pregnancy and continues into early lactation, has traditionally been interpreted as a depression in intake due to physical constraints. However, the rôle of physical constraints on intake has been overemphasized, particularly in early lactation. There is mounting evidence that the presence and mobilization of body reserves in early lactation play an important rôle in regulating intake at this time.Conceptually, the dip in intake in early lactation observed when cows have access to non-limiting foods can be accounted for by assuming that the cow has a desired level of body reserves. When the cow is not compromised, the changes with time in body reserves and the dip in intake represent the normal case and provide the basis against which to assess true depressions in intake which may occur when the cow is compromised by limiting nutrition or environment.The regulation of body reserves and intake in the periparturient cow is orchestrated through nervous and hormonal signals. Likely factors that are involved in intake regulation are reproductive hormones, neuropeptides, adrenergic signals, insulin and insulin resistance and leptin. Furthermore, oxidation of NEFA in the liver may result in feedback signals that reduce intake. The relative importance of these is discussed. A better understanding of the physiological signals involved in intake regulation and their interrelations with body weight regulation may provide important indicators of the degree of compromise that periparturient cows may experience.

scholarly journals Ribosomal stress-surveillance: three pathways is a magic number

2020 ◽  
Vol 48 (19) ◽  
pp. 10648-10661 ◽  
Author(s):  
Anna Constance Vind ◽  
Aitana Victoria Genzor ◽  
Simon Bekker-Jensen
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Map Kinases ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Magic Number ◽  
Physiological Role ◽  
Negative Effects ◽  
Mitogen Activated Protein ◽  
Activation Mechanisms

Abstract Cells rely on stress response pathways to uphold cellular homeostasis and limit the negative effects of harmful environmental stimuli. The stress- and mitogen-activated protein (MAP) kinases, p38 and JNK, are at the nexus of numerous stress responses, among these the ribotoxic stress response (RSR). Ribosomal impairment is detrimental to cell function as it disrupts protein synthesis, increase inflammatory signaling and, if unresolved, lead to cell death. In this review, we offer a general overview of the three main translation surveillance pathways; the RSR, Ribosome-associated Quality Control (RQC) and the Integrated Stress Response (ISR). We highlight recent advances made in defining activation mechanisms for these pathways and discuss their commonalities and differences. Finally, we reflect on the physiological role of the RSR and consider the therapeutic potential of targeting the sensing kinase ZAKα for treatment of ribotoxin exposure.

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