Dr Naomi Brooks & Dr Stuart Galloway
Health & Exercise Sciences Research Group, University of Stirling, UK

https://doi.org/10.36866/pn.97.21

The rapid and continuing rise in obesity throughout both the developed and developing world is a current critical world health issue. Increased levels of obesity are a major challenge to public health with obesity contributing to increased cases of type 2 diabetes, cardiovascular disease, stroke, cancer and loss of quality of life. Metabolic syndrome and type 2 diabetes are also key factors influencing cardiovascular disease risk. Further, location of adipose tissue – i.e. abdominal adipose and intra-abdominal (visceral) adipose tissue – is associated with increases in the risk of cardiometabolic disease. Morbidity and mortality from cardiometabolic disease put a great burden on individuals, families and communities and put an increased financial burden on health care systems.

At its most simple, obesity is considered to be caused by increased energy intake without concomitant energy usage. However, it is not that simple. Environmental and behavioural factors including increased calorie consumption and food intake (foods high in sugar and fat) can influence the energy imbalance. Decreases in physical activity also contribute, some would argue more so, to the obesity crisis. Physical inactivity and sedentary lifestyle are independent risk factors for metabolic disorders. Adequate physical activity is required for metabolic health and acts to reduce risk factors associated with atherosclerosis and metabolic disorders, particularly rectifying high blood pressure, insulin resistance, glucose intolerance, low HDL-cholesterol, high LDL-cholesterol, and high triglycerides. Physical activity in addition to reduced sedentary time (sitting less) is therefore recommended in both prevention and treatment of these metabolic disorders.

An increased body mass, measured by body mass index (BMI: mass (kg)/height (m)2), has been consistently reported to be linked to increased mortality and morbidity throughout the lifespan. The recommended BMI for a healthy individual is 18.5–24.9 kg/m2; overweight is defined as BMI of 25–29.9 kg/m2 and obese is defined as ≥30 kg/m2. However, BMI does not take into consideration body composition or location of fat mass.

Obese individuals develop health complications due to an increasing number and size of adipocytes (increasing fat mass). The increased size and number of adipocytes leads to dysfunction and cellular stress which contributes to insulin resistance, increased inflammation and increases in circulating lipids (for detailed review see Capurso & Capurso, 2012). Obese individuals develop resistance to the cellular effects of insulin, which displays as an impaired ability of insulin to stimulate glucose uptake from plasma into fat and muscle cells. It is thought that increased fatty acids (FAs) combined with lipid metabolites/signalling molecules interfere with the insulin-signalling pathway and can impair the actions of insulin and contribute to insulin resistance (Fig. 1). The resistance to the action of insulin results in elevated plasma glucose concentration (see Table 1 for normal values). The pancreas continues to secrete insulin in an attempt to reduce blood glucose concentration and eventually the beta-cells fail, and individuals with type 2 diabetes then require insulin therapy.

The adipocytes themselves are not inactive cells but are extremely important in human metabolism. Adipocytes secrete metabolically active proteins (adipokines) such as leptin, adiponectin and resistin, which contribute to healthy metabolism and are altered with obesity. Alterations of adipokine secretion lead to pathological consequences such as insulin resistance and increases in plasma lipid concentration. Adipocytes also contribute to the increased systemic inflammation noted with obesity, including increases in tumor necrosis factor-α, interleukin-6 and C-reactive protein, which are associated with insulin resistance and CVD. In addition, the increase in circulating FAs and other lipids leads to increased storage of fat in other tissues such as triglycerides in skeletal muscle and liver. While an increase in fat storage in muscle provides an important fuel source for some (i.e. athletes), in others such as non-active obese individuals, this has been further linked to insulin resistance (Fig. 1). Indeed, the capacity to oxidise FA seems an important determinant of the impact of caloric excess and obesity on insulin resistance. It is now well recognised that increasing the capacity of skeletal muscle to oxidise lipids, through exercise induced increases in mitochondrial volume, can effectively restore insulin sensitivity. This effect would likely be larger if both caloric restriction and exercise were adopted.

Skeletal muscle is an extremely important metabolic tissue and uses glucose and fat as well as amino acids for energy production. Glucose is a key fuel utilised in skeletal muscle during exercise and this uptake and usage is independent of insulin action. Thus, individuals who are insulin resistant, such as those with type 2 diabetes, can reduce blood glucose by increased use of their skeletal muscle mass. Physical activity, particularly in the fasted state, can also reduce the pathological complications of metabolic dysfunction in obesity by increasing oxidation of blood borne and intramuscular FAs, reducing the impact of these FAs on insulin resistance. Chronic bouts of contraction of skeletal muscle (e.g. exercise training) lead to production of myokines and anti-inflammatory responses, which reduce reactive oxygen species, mitochondrial dysfunction and ER stress, all of which contribute to reducing metabolic dysfunction. Interestingly, there appears to be a relationship between intensity and volume of physical activity and the cardiovascular/metabolic health outcomes. Research from competitive athletes suggests that their physical activity volume is conducted predominantly at low intensity (~75–80%) and with very little at moderate exercise (~5–10%) and a larger amount at vigorous intensity (~15–20%). Adopting these activity durations/distributions can produce greater cardiovascular and metabolic adaptations (Neal et al. 2013) in well-trained recreational athletes, which suggests that targeting physical activity intensity at the light and vigorous intensity ends of the spectrum could be more beneficial for health. Vigorous activity produces health improvements such as reducing adiposity and risk markers of cardiovascular and metabolic diseases (e.g. increases aerobic capacity and reduces fat mass). Thus, there are strong associations between aerobic fitness, amount of vigorous activity, and adiposity that are important in reducing cardiovascular and metabolic disease risk markers.

Physical activity and exercise have consistently been shown to improve health outcomes in individual and group exercise programmes, albeit with varying degrees of individual responsiveness. While there is consistent evidence that BMI is a predictor of all-cause mortality, and therefore reducing BMI is of benefit health-wise, there are a number of paradoxes to this thinking. Of particular interest is the FIT FAT phenomenon recently reviewed by McAuley & Blair (2011), which suggests obesity is not a risk factor for mortality in fit individuals. The FIT FAT phenomenon is based on evidence that obese individuals who are fit are at no greater risk for mortality than normal weight fit individuals. However, the likelihood of being fit is also related to BMI, with higher numbers of normal weight individuals being considered to have higher fitness levels compared to overweight individuals (i.e. NHANES, Duncan et al. 2010). These observations further highlight the importance of exercise and particularly moderate to vigorous exercise in maintaining health, regardless of body mass or BMI. While weight loss is important to obese and overweight individuals, increasing physical activity and exercise to improve fitness is of importance to healthy outcomes regardless of weight loss. This is a key aspect often missed when interpreting results of exercise programmes and when planning interventions for improvements in health.

An excellent recent example of a successful public health intervention involving a research programme of lifestyle intervention has been running for the last 4 years in Scotland. The Football Fans in Training (FFIT) is a 12-week, gender-sensitised weight management and physical activity programme delivered to groups of men at Scottish Premier League clubs. The programme has been led by the University of Glasgow and was developed to use scientific approaches to weight loss, physical activity and diet, which are delivered to participants at their football clubs. The aim of the intervention was to encourage individuals to make lifestyle changes to reduce their risk of ill health by losing weight, becoming more physically active and consuming a healthier diet. Individuals were recruited from football clubs throughout Scotland. After a successful pilot study (Gray et al. 2013) showed that the 12-week intervention was feasible and can have a positive effect on lifestyle choices, reduced obesity and increased physical activity, the project was expanded to include football clubs throughout Scotland.

The recent report on this study published in The Lancet (Hunt et al. 2014) details a follow-up of the 747 individuals who took part in the 12-week FFIT programme. Each week participants had one 90-minute session, which included combined advice on healthy diet with physical activity. After 12 weeks, average mass loss was 5.8 kg, waist circumference reduced by 6.7 cm, BMI by 1.9 kg/m2, body fat percentage by 3%, systolic BP by 8 mmHg and diastolic BP by 4 mmHg (all statistically significant). Improvements were reported in dietary intake with reduced fatty food intake, sugary food score, and alcohol consumption, and increased fruit and vegetable score (all significantly different from baseline). The 12 month follow-up reported waist circumference reduced from baseline by 7.3cm, BMI reduced by 1.8 kg/m2, body fat percentage by 2%, systolic BP by 8 mmHg and diastolic BP by 5 mmHg (all statistically significant). The alterations reported in diet were maintained at 12 months. Significant increases in self-esteem, mental and physical health, and quality of life were all noted after 12 weeks and remained higher than baseline at 12 months. The FFIT programme has been hugely successful at encouraging lifestyle changes and increases in physical activity for overweight and obese men. Furthermore, the study targeted a population who are generally reluctant to join exercise programmes, and there was a 90% retention of individuals in the programme – a key point in its ongoing success.

Another older success story of the positive effects of exercise and lifestyle changes on metabolic health is reported with the Diabetes Prevention Program, a large randomised clinical trial involving individuals who were at risk for developing type 2 diabetes in the USA (Knowler et al. 2002). The aim of the study was to investigate whether lifestyle intervention or treatment with metformin (a popular drug to treat diabetes) could prevent or delay the onset of diabetes. Participants in the study were at risk for type 2 diabetes, with BMI of ≥24 kg/m2 and fasting plasma glucose of 5.3 – 6.9 mmol/L. Individuals in the study were randomly assigned to one of three interventions: standard lifestyle recommendations with metformin (initially 850 mg once/day and increased to 850 mg twice/day after 1 month); standard lifestyle recommendations with placebo; or an intensive programme of lifestyle modifications. The intensive programme of lifestyle modifications involved a 16-lesson curriculum containing diet, exercise and behaviour modifications. The goal was to achieve and maintain a 7% weight reduction through low-calorie, low-fat diet and engage in physical activity of moderate intensity for at least 150 minutes/week. The study included 3234 individuals (average age 50.6 ±10.7 years) and the average follow-up was 2.8 years. At follow-up, the placebo group had incidence of diabetes with 11.0 cases/100 person years. The group given metformin had a reduced incidence of diabetes (7.8 cases/100 person years; 31% lower). However, the lifestyle intervention group had a significantly lower incidence of diabetes than both the placebo and the metformin group (4.8 cases/100 person years; 58% lower). The results show that individuals in the lifestyle group decreased energy intake by ~450 kcal/day and increased physical activity to the greatest degree. Thus, lifestyle interventions can be more effective than current prescription drugs for treating and preventing diabetes.

Finally, there has been a lot of recent attention on short-term high-intensity interval training (HIIT) and the benefits to metabolic health. Skeletal muscle is highly adaptable to exercise and short-duration high-intensity exercise bouts can significantly improve skeletal muscle metabolism. It appears that the disturbance in homeostasis at exercise onset, i.e. the beginning of a HIIT session, or the high rate of utilisation of glucose/glycogen is fundamental for upregulation of key regulators in skeletal muscle fat and carbohydrate metabolism. Thus, repeated rest-to-exercise transitions, which occur over a short period, appear to be a beneficial way to increase whole body fat metabolism. Adopting this approach in seven high intensity interval training sessions over 2 weeks led to an increase in whole body fat oxidation during exercise by 36%, and increased skeletal muscle capacity to oxidise FAs in women (Talanian et al. 2007). This type of exercise intervention has been reported to have great promise for individuals with impaired metabolic responses and has been shown to increase fat metabolism and reduce body fat stores in obese individuals. Alternatively, sprint interval training has also been shown to have similar effects on skeletal muscle metabolic adaptation in a time efficient manner (reviewed in Gibala et al. 2012). Furthermore, Gibala et al. (2012) discuss in detail how HIIT training has been used effectively to improve cardiorespiratory fitness in individuals at risk for CVD and metabolic disease.

In addition to the positive influences of exercise, dietary restriction and associated mass loss remain influential in the pursuit for health and reduction in obesity and consequential effects. A promising recent study reports evidence that the beta-cell dysfunction and insulin resistance characterised in type 2 diabetes can be reversed (Lim et al. 2011). The project undertaken at Newcastle University investigated the effects of a very low energy intake (600 kcal/day) on type 2 diabetes. Participants had type 2 diabetes (age 49.5 ± 2.5 years) and BMI of 33.6 ± 1.2 kg/m2. After 1 week of energy restriction, fasting plasma glucose concentration normalised to 5.9 mmol/L and remained stable throughout the 8-week study. Beta-cell function and hepatic insulin sensitivity were both restored to healthy function within the 8-week study timeframe. Average mass loss was 15 kg. These data clearly demonstrate the power of short-term reductions in energy intake alone, but exercise in combination with diet restriction would ensure healthy body composition changes to help retain lean mass while losing fat mass.

In summary, increasing physical activity and exercise, even in individuals who are obese, can have beneficial effects on reducing risk of mortality, increasing/maintaining muscle mass and improving metabolism in the face of mass loss, as well as overall health and wellbeing. The present article provides a very brief overview of a number of studies highlighting that provision of community based exercise programmes and appropriate lifestyle interventions are feasible and can be extremely beneficial for health outcomes in obese individuals. We have recently presented similar findings of a community-based exercise intervention in women from previously disadvantaged backgrounds in South African townships, demonstrating improvements in metabolic health are also observed in these individuals. Our data also demonstrate that community-based exercise programmes are feasible and effective in the South African township setting (Brooks et al. 2014).

It is clear from the details presented that there are a variety of ways to improve metabolic health including volume and intensity of exercise as well as dietary modification. While it is widely acknowledged that exercise is beneficial, we do not yet understand the optimal approach to exercise interventions. Perhaps the bigger question is how to maintain people in exercise programmes, which tend to have a large dropout rate. The Scottish FFIT programme provides evidence that retention and longer term behavioural changes are certainly possible in hard to reach groups when the correct approach is taken. It is clear that physical activity and exercise are beneficial for obese individuals with or without associated weight loss. As such, it is fundamental to incorporate a variety of exercise programmes and use the expertise of health scientists, exercise physiologists, behavioural change experts and nutritionists/dieticians when designing and implementing an exercise programme or physical activity intervention.

References

Brooks NE, Bowes J, Gava L, January N, Esterhuizen A & Myburgh KH (2014). Twelve weeks of community exercise improves health parameters in women living in a semi-rural township in South Africa. FASEB J 28:884.25.

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Duncan GE (2010). The ‘fit but fat’ concept revisited: population-based estimates using NHANES. Int J Behav Nutr Phys Act 24:7:47.

Gibala MJ, Little JP, MacDonald MJ & Hawley JA (2012). Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol 590.5, 1077–1084.

Gray CM, Hunt K, Mutrie N, Anderson AS, Treweek S & Wyke S (2013). Weight management for overweight and obese men delivered through professional football clubs: a pilot randomized trial. Int J Behav Nutr Phys Act 10.

Hunt K, Wyke S, Gray CM, Anderson AS, Brady A, Bunn C, Donnan PT, Fenwick E, Grieve E, Leishman J, Miller E, Mutrie N, Rauchhaus P, White A & Treweek S (2014). A gender-sensitised weight loss and healthy living programme for overweight and obese men delivered by Scottish Premier League football clubs (FFIT): a pragmatic randomised controlled trial. Lancet 383, 1211–1221.

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA & Nathan DM (2002). Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346, 393–403.

Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC & Taylor R (2011). Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54, 2506–2514.

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Talanian JL, Galloway SD, Heigenhauser GJ, Bonen A, Spriet LL (2007). Two weeks of high-intensity aerobic interval training increases the capacity for fat oxidation during exercise in women. J Appl Physiol 102, 1439–1447.

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