ArticleClinical nutrition (Edinburgh, Scotland)2016
Beneficial effects of β-sitosterol on type 1 cholecystokinin receptor dysfunction induced by elevated membrane cholesterol.
Article in Clinical nutrition (Edinburgh, Scotland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Cholesterol-dependent dynamic changes in the conformation of the type 1 cholecystokinin receptor affect ligand binding and G protein coupling.PLoS biology · 2024Article
- Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases.Natural products and bioprospecting · 2024Review
- Mechanism of Yixishu lotion in the treatment of vaginitis based on network pharmacology combined with experimental validation: an experimental research study.Annals of medicine and surgery (2012) · 2023Article
- Gender differences in the relationships between dietary phytosterols intake and prevalence of obesity in Chinese population.Food science & nutrition · 2023Article
- β-sitosterol inhibits trimethylamine production by regulating the gut microbiota and attenuates atherosclerosis in ApoEFrontiers in cardiovascular medicine · 2022Article
- Bioactive components, pharmacological effects, and drug development of traditional herbal medicineFrontiers in nutrition · 2022Review
- Structural and functional analysis of tomato sterol C22 desaturase.BMC plant biology · 2021Article
- Roles of Cholecystokinin in the Nutritional Continuum. Physiology and Potential Therapeutics.Frontiers in endocrinology · 2021Review
- Functional marriage in plasma membrane: Critical cholesterol level-optimal protein activity.British journal of pharmacology · 2020Review
- Changes in the plasma membrane in metabolic disease: impact of the membrane environment on G protein-coupled receptor structure and function.British journal of pharmacology · 2018Review
- Mechanisms of signalling and biased agonism in G protein-coupled receptors.Nature reviews. Molecular cell biology · 2018Review
- Cholecystokinin responsiveness varies across the population dependent on metabolic phenotype.The American journal of clinical nutrition · 2017Article
- Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target.Trends in endocrinology and metabolism: TEM · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe type 1 cholecystokinin receptor (CCK1R) mediates the actions of CCK to support nutritional homeostasis, including post-cibal satiety. However, elevated levels of membrane cholesterol, such as have been observed in metabolic syndrome, interfere with CCK stimulus-activity coupling at the CCK1R, thereby disrupting this important servomechanism. We hypothesize that reversal of the negative impact of cholesterol on this receptor could be useful in the management of obesity.
methodsWe have studied the effects of β-sitosterol, a phytosterol structurally related to cholesterol, on CCK receptor function. This included CCK binding and biological activity at wild type CCK1R and CCK2R, as well as at CCK1R in a high cholesterol environment, and at a CCK1R mutant, Y140A, which mimics the behavior of wild type receptor in high cholesterol.
resultsβ-sitosterol (100 μM and 10 μM) significantly improved the defective signaling of the CCK1R present in high cholesterol (p < 0.05), without affecting CCK binding affinity. This effect was absent at the CCK1R present in a normal cholesterol environment, as well as at the structurally-related CCK2R. Furthermore, the cholesterol-insensitive Y140A mutant of CCK1R was resistant to the effects of β-sitosterol.
conclusionThese data suggest that β-sitosterol affects CCK1R function in high cholesterol by competing with cholesterol at a receptor cholesterol-binding site and may shift its conformation toward normal. This phytosterol extends our understanding of the structure-activity relationships for developing a drug that can target the external surface of CCK1R. Since the concentrations of β-sitosterol shown to be effective in this study are similar to serum levels of this compound achievable during oral administration, it may be worthwhile to study possible beneficial effects of β-sitosterol in metabolic syndrome.
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