Acylated Ghrelin Response to Acute Exercise in Obesity (aeroghre)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00486161
Recruitment Status : Completed
First Posted : June 13, 2007
Last Update Posted : June 13, 2007
Information provided by:
Istituto Auxologico Italiano

Brief Summary:

Ghrelin is a GH-secretagogue gastrointestinal hormone that regulates feeding behavior by interacting directly with hypothalamic centers in concert with other negative and permissive neuromodulators. Ghrelin is involved in controlling energy balance in the short-term and long-term, and its levels are inversely related to the degree of obesity, insulin-resistance and energy accumulation. Consequently, obesity bears decreased ghrelin levels which increase upon weight loss, energy depletion and long-term exercise programs. Nevertheless, the role of acute exercise on the secretion of the bioactive component of ghrelin is yet unknown in conditions of normal and excessive body weight.

Our study examines acylated and total ghrelin secretion following a cycloergometric exercise test in obese and age- and sex-matched lean subjects to document if ghrelin components change as a function of fat accumulation, insulin homeostasis, growth hormone secretion, non-esterified fatty acid availability and exercise performance. Our study aims at testing the hypothesis that ghrelin components may be regulated by acute exercise, with concentrations at the exercise peak being related to acute metabolic homeostasis. Targetting this purpose may help to clarify ghrelin involvement in acute conditions unrelated to gastrointestinal activities.

Condition or disease

Detailed Description:
  1. Ghrelin is the natural ligand of the hypothalamic GH-secretagogue receptor (GHS-R)-1a (1). Over the time, it has been documented that ghrelin predominantly functions as a central modulator of energy homeostasis via NP-Y and AgRP-containing neurons located in the arcuate nucleus of the hypothalamus (2). It thus promotes the drive to eat and governs long-term energy accumulation; clearly, circulating ghrelin concentrations are related to energy balance based on the following evidences (3):

    • ghrelin levels are acutely modulated by food intake and glucose administration
    • long-term ghrelin homeostasis reflects adiposity, insulin resistance and chronic exercise
    • in fasting and postabsorptive conditions, a negative correlation exists between ghrelin and resting energy expenditure independent of variations in insulin levels, energy intake, body composition or body weight.

    In summary, circulating ghrelin levels are approximately 30% lower than normal; are inversely related to increasing body fat, leptin and insulin levels; and are far less responsive to post-meal inhibition than in controls (3).

  2. In the circulation, ghrelin is found as acylated and desacylated peptide. Ser(3)-octanoylation is a prerequisite for ghrelin biological activity (3). Des-octanoyl ghrelin variants have been additionally identified (4,5) and found to exert novel antiapoptotic effects in primary adult and cultured rat cardiomyocytes (6). Using specific immunoassays recognizing active (N-terminus) and total (N- plus C-terminus) ghrelin levels, assessment of circulating ghrelin concentrations helped to further discriminate specific functions of each at the hypothalamic level (7), on insulin sensitivity (8) or after bariatric surgery (9). Also, an association has been documented between obesity and total and acylated ghrelin concentrations, being respectively 30% and 56% lower than normal (10). Our laboratory showed previously that stratification of obese patients by the ratio of measured/predicted resting energy expenditure, allowed to detect a positive relationship between acylated ghrelin levels and the efficiency of energy expenditure (10). Speculatively, this could be interpreted as an obesity-related compensatory mechanism acting to contain the orexigenic signals afferent to the brain.
  3. Studies on ghrelin responsiveness to cycloergometer exercise, treadmill exercise or long-distance marathons, originally showed no variation of ghrelin secretion (11-13). More recently, significant decrements of ghrelin levels following acute exercise bouts has been observed in elite athletes and their healthy controls, as well as in lean individuals (14, 15). While these findings suggested a link of ghrelin suppression with GH rise on one side and appetite regulation upon exercise on the other, little is known on the metabolic mechanisms regulating ghrelin response to acute exercise in the lean and obese state.

Based on these observations, our comparative study aims at exploring the response of ghrelin components to a standardized maximal exercise test in the lean and obese state, to identify the neuroendocrine and metabolic predictors of ghrelin response in these groups and document if ghrelin components change as a function of fat accumulation, insulin homeostasis, growth hormone secretion, non-esterified fatty acid availability and exercise performance.

Study Type : Observational
Actual Enrollment : 16 participants
Observational Model: Case Control
Observational Model: Natural History
Time Perspective: Cross-Sectional
Time Perspective: Prospective
Official Title: Evaluation of Acylated Ghrelin Response Following Acute Exercise in Relation to Adiposity, Metabolic Homeostasis and Growth Hormone Secretion
Study Start Date : March 2004
Actual Study Completion Date : December 2006

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Ages Eligible for Study:   20 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • healthy status
  • lean (BMI < 25 kg/m2) and obese subjects (BMI>30 kg/m2)

Exclusion Criteria:

  • cardiovascular disease
  • gastrointestinal disease
  • diabetes mellitus
  • alcohol consumption (wine or equivalents) > 125 ml Day
  • physical inability

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00486161

IRCCS Istituto Auxologico Italiano, Ospedale San Giuseppe
Piancavallo di Oggebbio, Verbania, Italy, 28921
Sponsors and Collaborators
Istituto Auxologico Italiano
Principal Investigator: Paolo Marzullo, MD, PhD Division of General Medicine

Additional Information:

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00486161     History of Changes
Other Study ID Numbers: 18C403
First Posted: June 13, 2007    Key Record Dates
Last Update Posted: June 13, 2007
Last Verified: June 2007

Keywords provided by Istituto Auxologico Italiano:
Non-esterified fatty acids
Growth hormone
Cycloergometer exercise

Additional relevant MeSH terms:
Nutrition Disorders
Body Weight
Signs and Symptoms