Role of impulsivity and reward in the anti-obesity actions of 5-HT2C receptor agonists

2017 ◽  
Vol 31 (11) ◽  
pp. 1403-1418 ◽  
Author(s):  
Guy A Higgins ◽  
Fiona D Zeeb ◽  
Paul J Fletcher
Keyword(s):  
Lifestyle Modification ◽  
Conditioned Reward ◽  
Receptor Agonists ◽  
Subsequent Phase ◽  
Obese Subjects ◽  
Clinically Significant ◽  
Treatment Of Obesity ◽  
Phase Ii And Iii ◽  
Modest Effect

The selective 5-HT2C receptor agonist lorcaserin entered clinical obesity trials with the prevalent view that satiety was a primary mechanism of action. Subsequent Phase II and III trials demonstrated efficacy in terms of weight loss, although the overall effect size (~3% placebo-corrected change) is considered modest. Lorcaserin has been approved by the FDA for the treatment of obesity with lifestyle modification, but since its introduction in 2013 its sales are in decline, probably due to its overall modest effect. However, in some individuals, lorcaserin has a much more clinically significant effect (i.e. >10% placebo-corrected change), although what common features, if any, define these high responders is presently unknown. In the present article we highlight the evidence that alternative mechanisms to satiety may contribute to the anti-obesity effect of lorcaserin, namely effects on constructs of primary and conditioned reward and impulsivity. This may better inform the clinical evaluation of lorcaserin (and any future 5-HT2C receptor agonists) to subgroups of obese subjects characterized by overeating due to maladaptive impulsivity and reward mechanisms. One such population might be individuals diagnosed with binge eating disorder.

Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era

2020 ◽  
Vol 20 ◽  
Author(s):  
Giuseppe Lassandro ◽  
Valentina Palladino ◽  
Giovanni Carlo Del Vecchioa ◽  
Viviana Valeria Palmieri ◽  
Paola Carmela Corallo ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Treatment Options ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor ◽  
Related Quality ◽  
Health Related

Background and Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safety and effective for the treatment of pediatric ITP. The aim of our research is defining the role of thrombopoietin receptor agonists in the management of pediatric ITP. Method: This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in management of the disease. Results: Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Conclusion: Although TPO-RAs long term efficacy and safety still require further investigations, their use is gradually expanding in clinical practice of children with ITP.

Alcohol Use Disorder

2018 ◽  
Author(s):  
Igor Ponomarev
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Critical Discussion ◽  
Epigenetic Mechanisms ◽  
Future Directions ◽  
Clinically Significant ◽  
Early Life Exposures ◽  
The Brain ◽  
Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

Role of Nutrition Counseling and Lifestyle Modification in Managing Prediabetes

2021 ◽  
pp. 037957212110254
Author(s):  
Harleen Kaur ◽  
Neerja Singla ◽  
Rohini Jain
Keyword(s):  
Hemoglobin A1c ◽  
Lifestyle Modification ◽  
Fasting Blood Glucose ◽  
Nutrition Intervention ◽  
Control Group ◽  
Population Prevalence ◽  
Significant Difference ◽  
And Control ◽  
Experimental Group

Objective: India is the second country after China having the highest population prevalence of diabetes. Several research studies investigating diabetes have been done, but not much work has been done on prediabetes. The purpose of this study was to investigate the effect of nutrition and lifestyle modification on prediabetic females. Methods: A total of 120 prediabetic females from Ludhiana city were divided into 2 matched groups: control group (n = 60) and experimental group (n = 60). Impact of nutrition intervention for dietary and lifestyle modification (for 3 months) was assessed on the anthropometric, dietary, biochemical parameters, and diabetes risk score of the experimental group and control group (no intervention). Results: All the selected 120 subjects completed the study (experimental group = 60; control group = 60). There was significant difference in the changes between the 2 groups throughout the study. The fasting blood glucose and glycated hemoglobin A1c levels of the experimental group subjects reduced significantly ( P ≤ .01). However, no change was observed among the control group subjects. The lipid profile of the experimental group showed a significant improvement ( P ≤ .01). Conclusion: Nutrition counselling of the prediabetics regarding dietary and lifestyle modification is recommended so as to improve their metabolic control, thus preventing them from being diabetics.

scholarly journals An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

2021 ◽  
Vol 22 (15) ◽  
pp. 7975
Author(s):  
Saioa Gómez-Zorita ◽  
Iñaki Milton-Laskibar ◽  
Laura García-Arellano ◽  
Marcela González ◽  
María P. Portillo
Keyword(s):  
Adipose Tissue ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Current Evidence ◽  
Disease Outcomes ◽  
Lower Activation ◽  
Two Factors ◽  
Obese Subjects ◽  
Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

scholarly journals Differences in Salivary Proteins as a Function of PROP Taster Status and Gender in Normal Weight and Obese Subjects

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2244
Author(s):  
Melania Melis ◽  
Mariano Mastinu ◽  
Stefano Pintus ◽  
Tiziana Cabras ◽  
Roberto Crnjar ◽  
...  
Keyword(s):  
Food Preferences ◽  
Specific Weight ◽  
Normal Weight ◽  
Nutrition Status ◽  
Salivary Proteins ◽  
Specific Proteins ◽  
Obese Subjects ◽  
And Gender ◽  
Cystatin Sn

Taste plays an important role in processes such as food choices, nutrition status and health. Salivary proteins contribute to taste sensitivity. Taste reduction has been associated with obesity. Gender influences the obesity predisposition and the genetic ability to perceive the bitterness of 6-n-propylthiouracil (PROP), oral marker for food preferences and consumption. We investigated variations in the profile of salivary proteome, analyzed by HPLC-ESI-MS, between sixty-one normal weight subjects (NW) and fifty-seven subjects with obesity (OB), based on gender and PROP sensitivity. Results showed variations of taste-related salivary proteins between NW and OB, which were differently associated with gender and PROP sensitivity. High levels of Ps-1, II-2 and IB-1 proteins belonging to basic proline rich proteins (bPRPs) and PRP-1 protein belonging to acid proline rich proteins (aPRPs) were found in OB males, who showed a lower body mass index (BMI) than OB females. High levels of Ps-1 protein and Cystatin SN (Cyst SN) were found in OB non-tasters, who had lower BMI than OB super-tasters. These new insights on the role of salivary proteins as a factor driving the specific weight gain of OB females and super-tasters, suggest the use of specific proteins as a strategic tool modifying taste responses related to eating behavior.

scholarly journals Genetic Analysis of the Role of Pol II Holoenzyme Components in Repression by the Cyc8-Tup1 Corepressor in Yeast

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1535-1542 ◽  
Author(s):  
Mark Lee ◽  
Sukalyan Chatterjee ◽  
Kevin Struhl
Keyword(s):  
Transcriptional Repression ◽  
Detectable Effect ◽  
Genetic Screens ◽  
Phenotypic Analysis ◽  
Histone Tails ◽  
Pol Ii ◽  
Corepressor Complex ◽  
The Individual ◽  
Modest Effect

Abstract The Cyc8-Tup1 corepressor complex is targeted to promoters by pathway-specific DNA-binding repressors, thereby inhibiting the transcription of specific classes of genes. Genetic screens have identified mutations in a variety of Pol II holoenzyme components (Srb8, Srb9, Srb10, Srb11, Sin4, Rgr1, Rox3, and Hrs1) and in the N-terminal tails of histones H3 and H4 that weaken repression by Cyc8-Tup1. Here, we analyze the effect of individual and multiple mutations in many of these components on transcriptional repression of natural promoters that are regulated by Cyc8-Tup1. In all cases tested, individual mutations have a very modest effect on SUC2 RNA levels and no detectable effect on levels of ANB1, MFA2, and RNR2. Furthermore, multiple mutations within the Srb components, between Srbs and Sin4, and between Srbs and histone tails affect Cyc8-Tup1 repression to the same modest extent as the individual mutations. These results argue that the weak effects of the various mutations on repression by Cyc8-Tup1 are not due to redundancy among components of the Pol II machinery, and they argue against a simple redundancy between the holoenzyme and chromatin pathways. In addition, phenotypic analysis indicates that, although Srbs8–11 are indistinguishable with respect to Cyc8-Tup1 repression, the individual Srbs are functionally distinct in other respects. Genetic interactions among srb mutations imply that a balance between the activities of Srb8 + Srb10 and Srb11 is important for normal cell growth.

scholarly journals Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yawei Wang ◽  
Binlin Tang ◽  
Lei Long ◽  
Peng Luo ◽  
Wei Xiang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxidative Phosphorylation ◽  
Near Infrared ◽  
Mitochondrial Metabolism ◽  
Diet Induced Obesity ◽  
Adipose Tissue Macrophages ◽  
Inflammatory Activation ◽  
Treatment Of Obesity ◽  
Pharmaceutical Agents

AbstractPro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.

scholarly journals The Role of High Triglycerides Level in Predicting Cognitive Impairment: A Review of Current Evidence

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2118
Author(s):  
Alina Mihaela Dimache ◽  
Delia Lidia Șalaru ◽  
Radu Sascău ◽  
Cristian Stătescu
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Lifestyle Modification ◽  
Cognitive Disorders ◽  
Current Evidence ◽  
Barrier Dysfunction ◽  
Serum Triglycerides ◽  
Cerebral Amyloidosis ◽  
The Relationship

The burden of cognitive disorders is huge and still growing, however the etiology and the degree of cognitive impairment vary considerably. Neurodegenerative and vascular mechanisms were most frequently assessed in patients with dementia. Recent studies have shown the possible involvement of triglycerides levels in cognitive function through putative mechanisms such as brain blood barrier dysfunction or amyloid metabolism imbalance, but not all research in the field found this association. Several clinical studies evaluated the relationship between different forms of cognitive decline and levels of serum triglycerides, independent of other cardiovascular risk factors. This review focuses on the role of triglycerides in cognitive decline, cerebral amyloidosis and vascular impairment. Considering that the management of hypertriglyceridemia benefits from lifestyle modification, diet, and specific drug therapy, future studies are requested to appraise the triglycerides–cognitive impairment relationship.

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