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Acylated Ghrelin Response to Acute Exercise in Obesity (aeroghre)

This study has been completed.
Sponsor:
Information provided by:
Istituto Auxologico Italiano
ClinicalTrials.gov Identifier:
NCT00486161
First received: June 11, 2007
Last updated: June 12, 2007
Last verified: June 2007
  Purpose

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
Obesity

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Evaluation of Acylated Ghrelin Response Following Acute Exercise in Relation to Adiposity, Metabolic Homeostasis and Growth Hormone Secretion

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Further study details as provided by Istituto Auxologico Italiano:

Enrollment: 16
Study Start Date: March 2004
Study Completion Date: December 2006
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.

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00486161

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

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00486161     History of Changes
Other Study ID Numbers: 18C403
Study First Received: June 11, 2007
Last Updated: June 12, 2007
Health Authority: Italy: Ministry of Health

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

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

ClinicalTrials.gov processed this record on November 25, 2014