Acylated Ghrelin Response to Acute Exercise in Obesity
Condition: Obesity
MeSH terms: Obesity
Study type: Observational

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.
    

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.
    

Observational model: Case-Control
Time perspective: Other
Keywords: Obesity; Ghrelin; Non-esterified fatty acids; Growth hormone; Insulin; Cycloergometer exercise