Ghrelin and appetite control in humans—Potential application in the treatment of obesity

Previous studies have shown that mint scents reduce chocolate craving. However, two questions remain: whether the effect is an artifact of demand characteristics in which participants were aware that the study aimed to examine the effect of mint scent, and whether mint scent reduces appetite for foods generally other than chocolate. The present study took advantage of the fact that wearing face masks in public is becoming a standard norm because of the COVID-19 pandemic, to manipulate scent presentation to participants. We investigated the potential application of mint-scented masks for appetite control. Participants who were deceived that wearing masks were for consumer testing to eliminate demand characteristics rated their perceived wanting to eat for a variety of food images that had been preliminarily rated for perceived wanting while wearing a mint-scented mask (or an unscented control mask). The results showed that wearing a mint-scented compared to an unscented mask reduced perceived wanting for foods regardless of base wanting. The results demonstrate a novel potential application of mint-scented masks, namely appetite control, and replicates and extends the generalizability of past findings by excluding artifacts of demand characteristics.

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High Constitutive Signaling of the Ghrelin Receptor—Identification of a Potent Inverse Agonist

Molecular Endocrinology ◽

10.1210/me.2003-0069 ◽

2003 ◽

Vol 17 (11) ◽

pp. 2201-2210 ◽

Cited By ~ 329

Author(s):

Birgitte Holst ◽

Adam Cygankiewicz ◽

Tine Halkjær Jensen ◽

Michael Ankersen ◽

Thue W. Schwartz

Keyword(s):

Inositol Phosphate ◽

Inverse Agonist ◽

Negative Control ◽

Appetite Control ◽

Ghrelin Receptor ◽

Physiological Importance ◽

Gh Secretion ◽

293 Cells ◽

Treatment Of Obesity ◽

Motilin Receptor

Abstract Ghrelin is a GH-releasing peptide that also has an important role as an orexigenic hormone-stimulating food intake. By measuring inositol phosphate turnover or by using a reporter assay for transcriptional activity controlled by cAMP-responsive elements, the ghrelin receptor showed strong, ligand-independent signaling in transfected COS-7 or human embryonic kidney 293 cells. Ghrelin and a number of the known nonpeptide GH secretagogues acted as agonists stimulating inositol phosphate turnover further. In contrast, the low potency ghrelin antagonist, [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-substance P was surprisingly found to be a high potency (EC50 = 5.2 nm) full inverse agonist as it decreased the constitutive signaling of the ghrelin receptor down to that observed in untransfected cells. The homologous motilin receptor functioned as a negative control as it did not display any sign of constitutive activity; however, upon agonist stimulation the motilin receptor signaled as strongly as the unstimulated ghrelin receptor. It is concluded that the ghrelin receptor is highly constitutively active and that this activity could be of physiological importance in its role as a regulator of both GH secretion and appetite control. It is suggested that inverse agonists for the ghrelin receptor could be particularly interesting for the treatment of obesity.

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Appetite control

Journal of Endocrinology ◽

10.1677/joe.1.05866 ◽

2005 ◽

Vol 184 (2) ◽

pp. 291-318 ◽

Cited By ~ 333

Author(s):

Katie Wynne ◽

Sarah Stanley ◽

Barbara McGowan ◽

Steve Bloom

Keyword(s):

Energy Homeostasis ◽

Gut Hormones ◽

The Body ◽

Appetite Control ◽

Homeostatic Process ◽

The Past ◽

Regulate Food Intake ◽

Treatment Of Obesity ◽

Physiological Systems

Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits. Circulating gut hormones modulate these pathways acutely and result in appetite stimulation or satiety effects. This review discusses central neuronal networks and peripheral signals which contribute energy homeostasis, and how a loss of the homeostatic process may result in obesity. It also considers future therapeutic targets for the treatment of obesity.

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Roles of Cholecystokinin in the Nutritional Continuum. Physiology and Potential Therapeutics

Frontiers in Endocrinology ◽

10.3389/fendo.2021.684656 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laurence J. Miller ◽

Kaleeckal G. Harikumar ◽

Denise Wootten ◽

Patrick M. Sexton

Keyword(s):

Peptide Hormone ◽

Allosteric Modulators ◽

Clinical Failure ◽

Appetite Control ◽

Positive Allosteric Modulator ◽

Cholecystokinin Receptor ◽

Metabolic Physiology ◽

Treatment Of Obesity ◽

Potential Therapeutics

Cholecystokinin is a gastrointestinal peptide hormone with important roles in metabolic physiology and the maintenance of normal nutritional status, as well as potential roles in the prevention and management of obesity, currently one of the dominant causes of direct or indirect morbidity and mortality. In this review, we discuss the roles of this hormone and its receptors in maintaining nutritional homeostasis, with a particular focus on appetite control. Targeting this action led to the development of full agonists of the type 1 cholecystokinin receptor that have so far failed in clinical trials for obesity. The possible reasons for clinical failure are discussed, along with alternative pharmacologic strategies to target this receptor for prevention and management of obesity, including development of biased agonists and allosteric modulators. Cellular cholesterol is a natural modulator of the type 1 cholecystokinin receptor, with elevated levels disrupting normal stimulus-activity coupling. The molecular basis for this is discussed, along with strategies to overcome this challenge with a corrective positive allosteric modulator. There remains substantial scope for development of drugs to target the type 1 cholecystokinin receptor with these new pharmacologic strategies and such drugs may provide new approaches for treatment of obesity.

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The Potential Application of Melanotropin Ligands for the Treatment of Obesity and Related Disorders: Potential and Problems

Frontiers in Medicinal Chemistry ◽

10.2174/9781681082493116090007 ◽

2016 ◽

pp. 161-181

Author(s):

Victor J. Hruby ◽

Minying Cai

Keyword(s):

Potential Application ◽

Treatment Of Obesity

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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