CHAPTER 1: LITERATURE REVIEW
1.2 Efficacy of Exercise as a Strategy to Reduce Body Mass
1.4.3 Changes in Appetite Regulating Hormones in Response to Long Term
Study Selection
The primary outcome of interest in this review was changes in circulating ghrelin and peptide YY levels in response to statistically significant body composition changes. Inclusion criteria for studies (summarised in table 1.20) were:
• Published between 1985 and 2011.
• Written in the English language.
• Adults over 16 years old, classed as overweight and obese (>BMI 25 kg/m2).
• Interventions including an exercise/physical activity element designed to induce negative energy balance and significant body fat reduction (studies including a dietary and other interventions were included providing all groups were subject to the same intervention allowing exercise induced effects to be elucidated).
• Must include body mass and/or body fat measurements.
• Interventions >3 weeks in duration.
• Body mass and/or fat mass changes as a primary outcome of interest.
1.4.3.1 Changes in Ghrelin and Body Mass in Response to Chronic Exercise Participation in Overweight and Obese Individuals
There is convincing, consistent evidence that ghrelin is significantly up-regulated in response to exercise-induced body mass changes in lean and obese individuals.
Few studies observe the effects of exercise exclusively, most include some form of dietary intervention. As a result studies with dietary intervention were also included and eight relevant studies were identified, seven of which observed a
significant chronic up-regulation of ghrelin in response to a significant body mass reduction.
Significant reductions in body mass induce counterproductive changes in ghrelin levels in overweight women. Long term studies have consistently shown that ghrelin levels increase as an apparent defensive reaction to the depletion of body fat stores, and not due to the effects of exercise participation per se.
Significant, progressive increases in circulating ghrelin levels have been observed in overweight and obese women reducing body mass by ≥3kg, achieved through a combination of exercise and EI restriction in interventions (Foster-Schubert et al, 2005; Ata et al, 2010; Martins et al, 2010a). Such changes in acylated ghrelin levels, accompanied by an increase in fasting hunger and greater post-prandial suppression of hunger, have also been observed in women achieving this
magnitude of exercise-induced body mass reduction in body mass over twelve weeks (Martins et al, 2010a). This was the only study identified which measured both acylated and total ghrelin levels. Unlike a one year exercise only
intervention with a much greater sample size (Foster-Schubert et al, 2005), no change in total ghrelin was observed in this study; it is possible that this study lacked statistical power which many have prevented detection of changes in total ghrelin. However, results of all these interventions indicate that even a non-clinically significant body mass reduction (<5% change) may result in increased sensitivity of appetite regulation in these women.
The increase in ghrelin levels resulting from body mass reduction may also be threshold dependent. The mean body mass reductions in a large sample of
overweight women participating in a one year exercise intervention were modest (-1.4kg), but still sufficient to induce a progressive increase in total ghrelin levels which reached significance after twelve months. Although mean values indicated an increase in ghrelin occurred in the whole group, further analysis revealed that a significant 18% increase in ghrelin was observed only in those who reduced body mass by at least 3kg (Foster-Schubert et al, 2005). The authors attempted to prevent dietary changes but commented that the
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relatively modest changes in body mass were most probably indicative that these attempts failed, and compensatory changes in EI probably occurred. Since this increase in ghrelin levels is most likely a mechanism to preserve body fat stores in the face of depletion, it is perhaps not surprising that this mechanism is threshold dependent. Further evidence has reported that ghrelin levels normalise after stabilisation of body mass. An 8.5% reduction in body mass, induced by a six month diet and exercise intervention, was associated with an increase in ghrelin levels which returned top baseline values after participants maintained their stable, lower body mass for a further six months after the intervention concluded (Garcia et al, 2006). This provides further evidence that these observed increases in circulating ghrelin operate to increase EI and defend body fat stores, since they also diminish once body mass equilibrium is achieved once more.
This defensive up-regulation of ghrelin levels may not occur in more severely obese individuals, and hence may be dependent on initial adiposity. Such individuals have very disturbed ghrelin regulation, characterised by abnormally low ghrelin concentrations and an absence of normal meal-related fluctuations.
A three week intervention combining exercise, EI restriction, and counselling which resulted in a clinically significant 5% body mass reduction in a small sample of morbidly obese men and women (Management of Obesity, Scottish Intercollegiate Guidelines Network, 2010) induced no changes in total ghrelin levels after (Morpurgo et al, 2003). Additionally, normal ghrelin responses to meal ingestion were not restored either. This may indicate that the severely obese may find it easier, initially, to achieve a significant body mass reduction, since ghrelin does not respond in a counter-regulatory fashion, or could be indicative of a lack of statistical power due to the small sample size. The lack of response may also be a symptom of highly disturbed ghrelin regulation, or an indication that physiological mechanisms do not respond to changes in adiposity when obesity is severe. However it is not clear if ghrelin levels would
up-regulate after a certain degree of body mass reduction in these individuals, as has been observed in less obese individuals; larger interventions are required to clarify this issue.
139 Table 1.20 Evidence regarding the chronic effects of exercise on ghrelin concentrations in lean and overweight/obese men and women.
Authors No. of
length Type of intervention
Mean composed of 40%
carbohydrate, 30% protein and 30% fat. EI of diet was
varied depending on individual energy needs.
Participants were asked to progressively increase the number of steps taken per
day by 1500 until a maximum of 4500 more
steps per day than baseline levels was
reached.
Ghrelin levels increased by 17% following the intervention (p<0.01).
Ghrelin concentrations:
Baseline: 2.9 ± 1.7 ng ml-1 Post-intervention: 3.5 ± 1.7 ng ml-1
(mean ± SD) (n=87) or control stretchers group
Exercise intervention: 45 mins moderate intensity
aerobic exercise – 5 days/week for 12 months.
Control intervention: one 45 min stretching session once per week for 12
Ghrelin concentrations progressively increased over the course of the exercise
intervention (p<0.05). concentrations after 12 months exercising (p<0.001 compared with baseline; p<0.01
compared with body mass loss <3kg).
Changes in ghrelin concentrations:
Baseline ∆12 months
<0.5kg loss: 616 ± 63 3 ± 23 0.5-3kg loss: 589 ± 56 41 ± 31
>3kg loss: 560 ± 72 99 ± 30 (mean ± SEM, pg ml-1) No significant change in ghrelin in
stretchers (p>0.05).
Garcia et 48 Obese n=48 WL: Not WL: 12 months WL: Lifestyle intervention WL: Not Mean fasting ghrelin concentrations
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length Type of intervention
Mean al (2006)
Mexican-American women randomised to 2
groups:
program consisting of administering 120mg Orlistat 3 times a day,
classes with dietician aimed at reducing EI by 2092 kJ/day, and classes
with fitness instructor aimed at increasing
physical activity to 150mins/week, mainly
walking.
CON: received multivitamin tablets every
day, received no instruction.
33.9 ± 1.4 CON:
36.1 ± 1.2 (mean ± SD)
reported significantly increased after 6 months in WL group only (p<0.05), but concentrations had returned to baseline levels after 12 months (p<0.01 compared
with 6 month values).
There were no changes in ghrelin concentrations in CON group (p>0.05).
Fasting ghrelin concentrations:
Baseline 6 months 12 months WL: 589 ± 52 704 ± 64 541 ± 45 CON: 595 ± 48 580 ± 27 472 ± 42
(mean ± SD, pg ml-1) Baseline ghrelin concentrations were significantly correlated to BMI changes at
12 months in the WL group (r=0.33;
p=0.04) consisting of 5 sessions/week of treadmill
walking or running at 75%
maximal heart rate, in order to expend 2092 kJ
per session.
No effect of exercise*time on acylated ghrelin.
Fasting acylated ghrelin concentrations were significantly increased post-intervention (p<0.05), and a there was a significant 127% increase in the extent of post-prandial suppression of acylated ghrelin levels post-intervention (p=0.009).
Fasting acylated ghrelin concentrations:
Pre-intervention: 37.2 ± 18.2 Post-intervention: 51.7 ± 26.0
(mean ± SD, pmol L-1) Post-prandial ∆ acylated ghrelin
concentrations:
Pre-intervention: 12.4 ± 11.1 Post-intervention: 28.1 ± 21.4
(mean ± SD, pmol L-1) There were no changes in total ghrelin
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length Type of intervention
Mean
Fasting hunger sensations were increased after the intervention (p<0.01).
Morpurgo et al (2003)
10 severely obese participants (3 male, 7 female)
and 5 healthy, lean controls who
did not take part of energy-restricted diet (1200-7531 kJ/day; 21%
protein, 53%
carbohydrates, 26% lipids), exercise training (30 mins
cycle exercise 5 days/week, 50-70mins
leisure walking 2 days/week and 30 mins
indoor activity 5 days/week), psychological counselling and nutritional
education
At baseline, obese had significantly lower ghrelin levels, and fasting ghrelin levels
were not modified by meal ingestion compared to controls (p<0.05).
5% body mass reduction did not significantly affect ghrelin concentrations
in obese (p>0.05).
Baseline ghrelin concentrations:
Pre-prandial Post-prandial Lean 352.4 ± 176.7 199.0 ± 105.2 Obese 110.8 ± 69.7 91.8 ± 70.2 Basal ghrelin concentrations: in obese:
Pre-intervention: 110.8 ± 69.7 Post-intervention: 126.4 ± 108.6
(mean ± SD, pmol L-1)
Intervention aimed at decreasing EI by 20% and
increasing EE by 10%.
Participants received dietary advice and instruction from a personal
trainer, and had access to gym to complete exercise
or could exercise independently.
26.9 ± 2.9 (mean ± SD)
-11.7 ± 2.5 (mean ± SD)
Compared to baseline, ghrelin levels rose significantly by 21.2 ± 26.7%
post-intervention (p<0.001).
Ghrelin concentrations:
Pre-intervention: 1102.0 ± 464.8 Post-intervention: 1307.0 ± 562.5
(mean ± SD, pg ml-1)
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1.4.3.2 Changes in Peptide YY and Body Mass in Response to Chronic Exercise Participation in Overweight and Obese
Individuals
Studies observing peptide YY in response to long term exercise are very limited in number. Only three relevant studies could be identified, summarised in table 1.21, and results of these studies are not in full agreement. A significant
reduction in body fat in overweight adolescents, induced by eight months exercise participation, resulted in a 23% increase in peptide YY levels (Jones et al, 2009). These results have not been echoed in overweight adults; despite statistically significant reductions in body mass induced over three to six months exercise participation (mean losses -3.1 kg and -1.8kg), no change in peptide YY levels has been witnessed in small samples of overweight men and women (Martins et al, 2010a; Turner et al, 2010). From the limited evidence that exists no real conclusions can be drawn, but it seems peptide YY levels may be altered by modest body composition changes only in younger individuals. However, a clinically significant body mass reduction induced by a clinical intervention has been shown to result in a decrease in peptide YY levels in obese adults (Pfluger et al, 2007), therefore it may be that body mass changes in the exercise studies were not large enough to induce changes in peptide YY. Further investigation is needed to elucidate the effects of exercise and body mass reduction on peptide YY levels on overweight and obese, as current evidence indicates a possible effect, but is too limited to be conclusive.
143 Table 1.21 Evidence table regarding the chronic effects of exercise on peptide YY concentrations in adults.
Authors No. of
adolescents n=12
15.3 ± 0.5
Post-intervention, peptide YY levels had significantly
↑ by 23% (p=0.05).
Peptide YY concentrations:
Pre-intervention: 171.2 ± 63.2 Post-intervention: 209.8 ± 78.9
(mean ± SD, pg ml-1) consisting of 5 sessions/week to expend 2092
kJ per session
30.1 ± 2.3
No significant effect on peptide YY concentrations (p>0.05).
Peptide YY concentrations:
Pre-intervention: 10.6 ± 5.5 Post-intervention: 10.3 ± 4.8
(mean ± SD, pmol L-1)
There was no change in recorded EI (p>0.05).
EI:
Pre-intervention: 9.41 ± 2.38 Post-intervention: 9.31 ± 2.79
(mean ± SD, MJ) sessions at 50%
VɺO2max and working up to
four 60 mins sessions at 70%
VɺO2max per
There were no significant differences in peptide YY concentrations between groups at baseline, post-intervention, or after 2 weeks of detraining (p>0.05).
There was no significant effect of the exercise intervention of peptide YY concentrations (p>0.05).
Peptide YY concentrations:
Exercise Control Baseline: 189 ± 51 192 ± 93 Week 24: 171 ± 38 199 ± 72 Week 26: 168 ± 72 187 ± 67
(mean ± SD, pg m-l-1)