Publications by authors named "S L Deschaine"
BACKGROUNDStudies have demonstrated the role of ghrelin in alcohol-related behaviors and consumption. Blockade of the growth hormone secretagogue receptor (GHSR), which is the ghrelin receptor, has been shown to decrease alcohol drinking and reward-related behaviors across several animal models. We previously conducted a human study testing a GHSR inverse agonist/competitive antagonist, PF-5190457, in individuals who are heavy drinkers and showed its safety when coadministered with alcohol.
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- The study examines the role of the ghrelin receptor (GHSR) in feeding behaviors and diet-induced obesity (DIO) by comparing global GHSR-KO and wild-type (WT) rats on high-fat and regular diets over 12 months.
- Findings reveal that GHSR gene deletion protects male rats from DIO, decreases their food intake on high-fat diets, and enhances thermogenesis and brain glucose uptake, while these effects were not observed in female rats.
- The use of a GHSR inverse agonist reduced food intake induced by ghrelin in males and lower binge-eating in both sexes, indicating GHSR as a potential target for obesity treatments.
Article Synopsis
- - The study explores how the ghrelin receptor (GHSR) influences feeding behaviors and diet-induced obesity (DIO) through research on gene deletion in male and female rats over a year on a high-fat diet (HFD).
- - Findings indicate that deleting the GHSR gene protects male rats from DIO and decreases their food intake, while having different effects for females.
- - The research also reveals that GHSR deletion enhances energy burning and alters brain glucose metabolism in males, suggesting GHSR could be a key target for obesity treatments.
Preclinical and clinical studies have identified the ghrelin receptor [growth hormone secretagogue receptor (GHSR)1a] as a potential target for treating alcohol use disorder. A recent phase 1a clinical trial of a GHSR1a antagonist/inverse agonist, PF-5190457, in individuals with heavy alcohol drinking identified a previously undetected major hydroxy metabolite of PF-5190457, namely PF-6870961. Here, we further characterized PF-6870961 by screening for off-target interactions in a high-throughput screen and determined its in vitro pharmacodynamic profile at GHSR1a through binding and concentration-response assays.
View Article and Find Full Text PDFUnhealthy alcohol consumption is a global health problem. Adverse individual, public health, and socioeconomic consequences are attributable to harmful alcohol use. Epidemiological studies have shown that alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) are the top two pathologies among alcohol-related diseases.
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