Obesity is a global pandemic and its prevalence among children and adolescents has also increased worldwide, becoming a serious public health problem . In China, nearly 215 million people are overweight or obese, and 12% of these are children (< 17-years-old), as estimated by the 2002 China National Nutrition and Health Survey . Obesity in childhood has been associated with an increased risk of diabetes, hypertension, cardiovascular disease and various cancers in adulthood [3, 4]. Therefore, preventing and treating obesity in children and adolescents is crucial.
The causes of childhood obesity are complex and multifaceted involving genetic factors, environmental, and behavioral factors. The current worldwide epidemic of obesity is believed to be attributable to the modern living environment which promotes a sedentary lifestyle and excessive consumption of calorie-dense food. Accordingly, a lifestyle modification including a healthy diet and increased physical activity has been recommended as the cornerstone of prevention and treatment of obesity. Physical activity increases energy expenditure and, in combination with a healthy diet, is effective in inducing weight loss. However, the reduced weight achieved through weight loss programs is hard to maintain over the longterm. The failure to achieve longterm weight loss is believed to be caused by compensatory changes in appetite and energy expenditure elicited by exercise and dieting. Currently, a complete understanding of the relationship between exercise, appetite regulation, and weight management is lacking.
Recent research has revealed that appetite-regulating hormones might play an important role in moderating the interrelationship between exercise and dieting, appetite, and weight regain. Among various potential appetite-regulating hormones, the gastrointestinal hormones, ghrelin, peptide YY (PYY), cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) are well studied. Ghrelin is the only hormone that has been shown to be orexigenic, while PYY, CCK, and GLP-1 are satiety regulatory hormones [5, 6]. These hormones are episodic hormonal signals occurring in unison with episodes of eating. They signal satiation and satiety either via the vagus nerve (which connects the gut to the brain) or via blood perfusing the hypothalamus.
It is accepted that in response to weight loss, counter-regulatory adaptations develop in the appetite regulatory system, including the gastrointestinal hormones, defending impositions that promote a negative energy balance. Different weight loss intervention approaches are likely to cause different counter-regulatory adaptations in terms of the content and the magnitude of the response. There is some evidence suggesting that diet-induced weight loss is associated with a compensatory increase in total ghrelin (GT) plasma levels and a blunted postprandial release of PYY and GLP-1 [7, 8]. Exercise-induced weight loss may increase the drive to eat, as shown by increased levels of acylated ghrelin (AG) and subjective feelings of hunger in fasting, but it may also improve satiety as evidenced by an increase in the late postprandial release of GLP-1 after exercise training .
Few studies have investigated the combined effect of exercise and dieting on appetite in children and adolescents. Based on the limited data, it appears that ghrelin levels increase after a weight reduction program, with no change in PYY levels [10–13]. Similarly, we have observed an increase in ghrelin concentrations after weight loss in adolescents who participated in an exercise and diet intervention for four weeks in a summer camp program in a previous study (unpublished data).
Recently, the effect of high altitude on appetite regulation has attracted researchers’ interest. It is a widely observed phenomenon that a high altitude can induce loss of appetite [14–16]. In many studies, loss of appetite and the resulting decrease in energy intake have been attributed to acute mountain sickness (AMS), symptoms of which include headache and anorexia. However, loss of appetite cannot merely be a by-product of AMS because anorexia and weight loss still persist when symptoms of AMS have subsided . Furthermore, studies conducted in normobaric hypoxia chambers, where other environmental stressors associated with high altitude are eliminated (extreme cold and physical exertion), have demonstrated that hypoxia per se can cause reduced appetite and energy intake, and loss of body weight . It has been suggested that the effect of hypoxia on appetite is mediated by the changes in gastrointestinal hormones [19–22].
It is perceivable that to promote success in longterm weight loss, hypoxia can be implemented in a traditional diet and exercise weight loss program, because the negative effect of hypoxia on appetite might be able to balance the positive effect of diet and exercise. Exercise and hypoxia have been used in combination in sports to induce maximal increase in aerobic endurance in athletes, but have rarely been used in weight loss, especially in children and adolescents. We have run several sessions of weight loss summer camps designed for obese adolescents in Shanghai, China. The effect of exercise and hypoxia on weight loss has been explored in our preliminary studies and interesting results have been generated [23, 24]. As such, we are now designing a randomly controlled trial to systematically investigate the longterm weight loss effect of exercise with hypoxia in obese adolescents and determine the mediating effect of the gastrointestinal hormones. We hypothesize that: 1) exercise and hypoxia will have an additive effect on weight loss via increasing energy expenditure and suppressing appetite; 2) hypoxia use will lead to less rebound of weight loss after intervention due to its potential negating effects on compensatory changes in appetite elicited by exercise and diet in a traditional weight loss program; and 3) changes in gastrointestinal hormones (including ghrelin, PYY, CCK, and GLP-1), as well as in cytokine interleukin (IL)-6, will be associated with changes in body weight after the intervention and during follow-up.
The aims of this randomized controlled trial (RCT) are to evaluate the effectiveness of intermittent hypoxia and exercise, in combination with a balanced diet, on inducing short- and longterm fat loss in Chinese children and adolescents, and to determine the molecular mechanisms behind the benefits of hypoxia in enhancing weight loss.