Search

Your search keyword '"Kevin Holsapple"' showing total 2 results
Start Over Author "Kevin Holsapple" Journal plos one
2 results on '"Kevin Holsapple"'

1. Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight.

Author

Carrie McMahon, James L Trevaskis, Christoph Carter, Kevin Holsapple, Kirsten White, Moupali Das, Sean Collins, Hal Martin, and Leigh Ann Burns-Naas

Subjects
Medicine, Science
Abstract

An increasing prevalence of overweight and obesity in people living with HIV has been associated with initiation of antiretroviral therapy with integrase strand transfer inhibitors (INSTIs). An off-target inhibition of the endogenous ligand binding to the human melanocortin 4 receptor (MC4R) has been suggested as a potential mechanism for clinical body weight gain following initiation of dolutegravir, an INSTI. In this study, we interrogated several INSTIs for their capacity for antagonism or agonism of MC4R in an in vitro cell-based assays including at concentrations far exceeding plasma concentrations reached at the recommended dosages. Our results indicate that while INSTIs do exhibit the capacity to antagonize MC4R, this occurs at concentrations well above predicted clinical exposure and is thus an implausible explanation for INSTI-associated weight gain.

Published
2020
Full Text
View/download PDF

2. Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight

Author

Kevin Holsapple, Moupali Das, Sean E Collins, Carrie McMahon, James L. Trevaskis, Leigh Ann Burns-Naas, Kirsten White, Hal Martin, and Christoph C Carter

Subjects
0301 basic medicine, RNA viruses, Physiology, HIV Infections, Pharmacology, Overweight, Weight Gain, Pathology and Laboratory Medicine, chemistry.chemical_compound, Binding Analysis, 0302 clinical medicine, Mathematical and Statistical Techniques, Immunodeficiency Viruses, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Receptor, Multidisciplinary, biology, Vaccination and Immunization, Integrase, Curve Fitting, Melanocortin 4 receptor, Physiological Parameters, Medical Microbiology, Viral Pathogens, Dolutegravir, Viruses, Medicine, Receptor, Melanocortin, Type 4, medicine.symptom, Melanocortin, Pathogens, Cell Binding Assay, Research Article, Science, 030106 microbiology, Immunology, Antiretroviral Therapy, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Antiviral Therapy, Retroviruses, medicine, Humans, HIV Integrase Inhibitors, Obesity, Microbial Pathogens, Chemical Characterization, business.industry, Body Weight, Lentivirus, Organisms, Biology and Life Sciences, HIV, medicine.disease, chemistry, biology.protein, Preventive Medicine, business, Weight gain, Mathematical Functions
Abstract

An increasing prevalence of overweight and obesity in people living with HIV has been associated with initiation of antiretroviral therapy with integrase strand transfer inhibitors (INSTIs). An off-target inhibition of the endogenous ligand binding to the human melanocortin 4 receptor (MC4R) has been suggested as a potential mechanism for clinical body weight gain following initiation of dolutegravir, an INSTI. In this study, we interrogated several INSTIs for their capacity for antagonism or agonism of MC4R in an in vitro cell-based assays including at concentrations far exceeding plasma concentrations reached at the recommended dosages. Our results indicate that while INSTIs do exhibit the capacity to antagonize MC4R, this occurs at concentrations well above predicted clinical exposure and is thus an implausible explanation for INSTI-associated weight gain.

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results