scholarly journals Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications

2010 ◽  
Vol 208 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Vijay K. Yadav ◽  
Franck Oury ◽  
Kenji F. Tanaka ◽  
Tiffany Thomas ◽  
Ying Wang ◽  
...  
Keyword(s):  
Food Intake ◽  
Gene Deletion ◽  
Selective Inhibition ◽  
Specific Gene ◽  
Serotonin Synthesis ◽  
Viable Option ◽  
Therapeutic Implications ◽  
Temporal Specificity ◽  
Specific Antagonist ◽  
Arcuate Nuclei

Recent evidence indicates that leptin regulates appetite and energy expenditure, at least in part by inhibiting serotonin synthesis and release from brainstem neurons. To demonstrate that this pathway works postnatally, we used a conditional, brainstem-specific mouse CreERT2 driver to show that leptin signals in brainstem neurons after birth to decrease appetite by inhibiting serotonin synthesis. Cell-specific gene deletion experiments and intracerebroventricular leptin infusions reveal that serotonin signals in arcuate nuclei of the hypothalamus through the Htr1a receptor to favor food intake and that this serotonin function requires the expression of Creb, which regulates the expression of several genes affecting appetite. Accordingly, a specific antagonist of the Htr1a receptor decreases food intake in leptin-deficient but not in Htr1a−/− mice. Collectively, these results establish that leptin inhibition of serotonin is necessary to inhibit appetite postnatally and provide a proof of principle that selective inhibition of this pathway may be a viable option to treat appetite disorders.

Dietary intake of tryptophan tied emotion-related impulsivity in humans

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Florian Javelle ◽  
Descartes Li ◽  
Philipp Zimmer ◽  
Sheri L. Johnson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Food Intake ◽  
Essential Amino Acid ◽  
Food Habits ◽  
Psychological Disorder ◽  
Serotonin Synthesis ◽  
Amino Acid Tryptophan ◽  
Pass Through ◽  
Three Factor

Abstract. Emotion-related impulsivity, defined as the tendency to say or do things that one later regret during periods of heightened emotion, has been tied to a broad range of psychopathologies. Previous work has suggested that emotion-related impulsivity is tied to an impaired function of the serotonergic system. Central serotonin synthesis relies on the intake of the essential amino acid, tryptophan and its ability to pass through the blood brain barrier. Objective: The aim of this study was to determine the association between emotion-related impulsivity and tryptophan intake. Methods: Undergraduate participants (N = 25, 16 women, 9 men) completed a self-rated measure of impulsivity (Three Factor Impulsivity Index, TFI) and daily logs of their food intake and exercise. These data were coded using the software NutriNote to evaluate intakes of tryptophan, large neutral amino acids, vitamins B6/B12, and exercise. Results: Correlational analyses indicated that higher tryptophan intake was associated with significantly lower scores on two out of three subscales of the TFI, Pervasive Influence of Feelings scores r =  –.502, p < . 010, and (lack-of) Follow-Through scores, r =  –.407, p < . 050. Conclusion: Findings provide further evidence that emotion-related impulsivity is correlated to serotonergic indices, even when considering only food habits. It also suggests the need for more research on whether tryptophan supplements might be beneficial for impulsive persons suffering from a psychological disorder.

scholarly journals Gastric Sensory and Motor Functions and Energy Intake in Health and Obesity—Therapeutic Implications

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1158
Author(s):  
Lizeth Cifuentes ◽  
Michael Camilleri ◽  
Andres Acosta
Keyword(s):  
Energy Consumption ◽  
Gastric Emptying ◽  
Food Intake ◽  
Gastric Volume ◽  
Obesity Management ◽  
Bariatric Endoscopy ◽  
Motor Functions ◽  
Therapeutic Implications ◽  
Intestinal Functions

Sensory and motor functions of the stomach, including gastric emptying and accommodation, have significant effects on energy consumption and appetite. Obesity is characterized by energy imbalance; altered gastric functions, such as rapid gastric emptying and large fasting gastric volume in obesity, may result in increased food intake prior to reaching usual fullness and increased appetite. Thus, many different interventions for obesity, including different diets, anti-obesity medications, bariatric endoscopy, and surgery, alter gastric functions and gastrointestinal motility. In this review, we focus on the role of the gastric and intestinal functions in food intake, pathophysiology of obesity, and obesity management.

von Willebrand Factor and Venous Thromboembolism: Pathogenic Link and Therapeutic Implications

2017 ◽  
Vol 44 (03) ◽  
pp. 249-260 ◽  
Author(s):  
Paolo Calabrò ◽  
Felice Gragnano ◽  
Enrica Golia ◽  
Erik Grove
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Von Willebrand Factor ◽  
Gene Mutations ◽  
Selective Inhibition ◽  
Therapeutic Implications ◽  
Vein Thrombosis ◽  
A Disintegrin And Metalloproteinase ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractVenous thromboembolism (VTE) is a frequent cause of disability and mortality worldwide. Von Willebrand factor (VWF) is a major determinant of hemostasis and clot formation, in both arteries and veins. Although VWF is mainly known for its role in arterial thrombosis, several studies suggest a pathogenic role for VWF and its regulator ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in venous thrombosis. Nongenetic and genetic factors, including gene mutations and polymorphisms, aging, hormone status, ABO blood groups, and systemic inflammation, have been involved in the modulation of both VTE predisposition and plasma levels of VWF. In several clinical settings, including inflammatory disease and cancer, VWF and ADAMTS-13 are currently investigated as possible determinants of vein thrombosis. These data indicate VWF as a potential therapeutic target in the management of VTE. Several studies report unselective antagonism of VWF for drugs used in daily clinical practice, including heparin and statins. Selective inhibition of VWF pathway has recently been tested in animal models of arterial and venous thrombosis as a novel therapeutic strategy to prevent platelet aggregation and thrombosis, promote vein lumen recanalization, and improve vein valve competency with excellent safety profile. In this review, we summarize the role of VWF in VTE, focusing on clinical and potential therapeutic implications.

scholarly journals A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9

2015 ◽  
Vol 113 (2) ◽  
pp. 338-343 ◽  
Author(s):  
Kelli J. Carroll ◽  
Catherine A. Makarewich ◽  
John McAnally ◽  
Douglas M. Anderson ◽  
Lorena Zentilin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Gene Deletion ◽  
Disease Modeling ◽  
Embryonic Lethality ◽  
Null Alleles ◽  
Specific Gene ◽  
Specific Expression ◽  
Guide Rna ◽  
Cardiac Gene ◽  
Genomic Editing

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)9 genomic editing has revolutionized the generation of mutant animals by simplifying the creation of null alleles in virtually any organism. However, most current approaches with this method require zygote injection, making it difficult to assess the adult, tissue-specific functions of genes that are widely expressed or which cause embryonic lethality when mutated. Here, we describe the generation of cardiac-specific Cas9 transgenic mice, which express high levels of Cas9 in the heart, but display no overt defects. In proof-of-concept experiments, we used Adeno-Associated Virus 9 (AAV9) to deliver single-guide RNA (sgRNA) that targets the Myh6 locus exclusively in cardiomyocytes. Intraperitoneal injection of postnatal cardiac-Cas9 transgenic mice with AAV9 encoding sgRNA against Myh6 resulted in robust editing of the Myh6 locus. These mice displayed severe cardiomyopathy and loss of cardiac function, with elevation of several markers of heart failure, confirming the effectiveness of this method of adult cardiac gene deletion. Mice with cardiac-specific expression of Cas9 provide a tool that will allow rapid and accurate deletion of genes following a single injection of AAV9-sgRNAs, thereby circumventing embryonic lethality. This method will be useful for disease modeling and provides a means of rapidly editing genes of interest in the heart.

scholarly journals Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Kohei Ueda ◽  
Mitsuhiro Nishimoto ◽  
Daigoro Hirohama ◽  
Nobuhiro Ayuzawa ◽  
Wakako Kawarazaki ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Gene Deletion ◽  
Specific Gene

Nociceptor-specific gene deletion using heterozygous NaV1.8-Cre recombinase mice

Pain ◽  
2005 ◽  
Vol 113 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Caroline L. Stirling ◽  
Greta Forlani ◽  
Mark D. Baker ◽  
John N. Wood ◽  
Elizabeth A. Matthews ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Cre Recombinase ◽  
Specific Gene

scholarly journals Positive regulation of MarR-type regulator slnO and improving salinomycin production of Streptomyces albus by multiple transcriptional regulations

2022 ◽  
Author(s):  
Hongrui Zhang ◽  
Weiwei Chen ◽  
Xinyi Wang ◽  
Yongquan Li ◽  
Zhenhong Zhu
Keyword(s):  
Gene Deletion ◽  
High Yield ◽  
Specific Gene ◽  
Wild Type ◽  
Yield Strain ◽  
Positive Regulation ◽  
Over Expression ◽  
Streptomyces Albus ◽  
Regulation Strategies ◽  
Expression Strain

The purpose of this study is to explore the function of MarR-family regulator slnO. In addition, the high-yield strain of salinomycin was constructed by using combined regulation strategies. Firstly the slnO gene over-expression strain (GO) was constructed in Streptomyces albus. Compared to wild type (WT) strain，salinomycin production in GO strain was increased about 28%. Electrophoretic mobility gel shift assays (EMSAs) confirmed that SlnO protein can bind specifically to the intergenic region of slnN-slnO, slnQ-slnA1 and slnF-slnT. qRT-PCR experiments also showed that slnA1, slnF, and slnT1 were significantly up-regulated, while the expression level of the slnN gene was down-regulated in GO strain. Secondly, slnN gene deletion strain (slnNDM) was used as the starting strain, and the pathway specific gene slnR in salinomycin gene cluster was over expressed in slnNDM. The new strain was named ZJUS01. The yield of salinomycin in ZJUS01 strain was 25% and 56% higher than that in slnNDM strain and WT strain. Above results indicate that the slnO gene has a positive regulation effect on the biosynthesis of salinomycin. Meanwhile, the yield of salinomycin could be greatly increased by manipulating multiple transcriptional regulations.

scholarly journals Gfi1-Cre knock-in mouse line: A tool for inner ear hair cell-specific gene deletion

genesis ◽  
2010 ◽  
Vol 48 (6) ◽  
pp. 400-406 ◽  
Author(s):  
Hua Yang ◽  
Jean Gan ◽  
Xiaoling Xie ◽  
Min Deng ◽  
Liang Feng ◽  
...  
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Gene Deletion ◽  
Specific Gene ◽  
Mouse Line
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