**5. Conclusions**

obese individuals. Although no significant difference between groups were observed, daily steps increased, and time of TV viewing, dietary intake, body fat percentage, waist and hip circumference significantly decreased after both interventions. Only stepping during watching TV could be a feasible approach for improving obesity. In the modern world, walking in a break during work is effective for weight loss. Levine and Miller [42] investigated whether the change of work environment affect individuals' energy expenditure at workplace. The vertical workstation that allows obese workers to use a personal computer while walking on a treadmill was established. The mean energy expenditure while walking at workplace was 191 kcal per hour, which was significantly higher than energy expenditure while seated at work (72 kcal per hour). This amount of energy expenditure could be equal to a weight loss of 20–30 kg per year. Furthermore, they assessed the effect of using an office-place stepping device housed under a desk on workers' energy expenditure [43]. The mean increase of energy expenditure in obese office workers was 335 kcal per hour, which could be equal to a weight loss of 20 kg per year. Changing living environments to change sedentary behavior will increase NEAT and decrease body weight. Each NEAT is small; however, "Many a little makes a mickle." To increase NEAT should be effective for improving obesity (**Figure 1**). NEAT is intricately regulated by endocrine, genetic, and sociological factors [39]. Sarcolipin [44] and ventromedial hypothalamic melanocortin receptor [45] have been of current interest as new mediators of NEAT. Sarcolipin, which consists of 31 amino acids and is highly expressed in skeletal muscle, plays a role in energy expenditure. Sopariwala et al. [44] showed that sarcolipin overexpression mice are more resistant to fatigue and more physically active compared with wild type. This newly identified regulator may increase non-shivering thermogenesis in humans [45] and could be effective to increase energy expenditure and control weight gain in obese individuals [46]. The ventromedial hypothalamus also has an important role in regulating energy balance, and the brain melanocortin system not only decreases appetite but increases physical activity [45, 47]. Gavini et al. [48] showed that intra-ventromedial hypothalamus melanocortin receptor activation increased physical activity and induced the elevation of mRNA expression of mediators of energy expenditure such as uncoupling proteins, peroxisome proliferator-activated receptors, peroxisome proliferatoractivated receptor gamma coactivator 1-α, and AMP-activated protein kinase. Modulating melanocortin receptors in the ventromedial hypothalamus may contribute to increase of NEAT. Identifying such novel mechanisms to increase energy expenditure is expected to be applied in the treatment of obesity. Moreover, the significant associations of NEAT with metabolic diseases such as type 2 diabetes, hypertension, and dyslipidemia have been identified [49–53]. NEAT intervention in addition to structured exercise prescription certainly improves obesity and metabolic diseases. To elucidate the effectiveness of NEAT for metabolic diseases, and further CVD, as well as obesity, well-designed longitudinal studies in humans are warranted. On the other hand, how to measure NEAT accurately under freeliving (accelerometry, doubly labeled water method, or a completely new method?) and how to intervene NEAT (recommendation or supervised program?) are still unknown. The development of measurement and intervention method of NEAT will be needed to conduct

140 Adiposity - Epidemiology and Treatment Modalities

such clinical studies.

Exercise interventions are essential for the management of obesity. However, exercise alone is not sufficient for long-term weight loss and improving CVD risk factors. Diet seems to be more effective for treating obesity than exercise. On the other hand, exercise improves cardiorespiratory fitness and skeletal muscle fitness, which leads to prevent sarcopenic obesity in the elderly. Exercise therapy should be performed in conjunction with diet therapy to improve obesity. Although a number of systematic reviews have been conducted to assess the effectiveness of exercise for obesity, small number of subjects, short duration, and the heterogeneity of exercise modes between clinical studies makes it difficult to conclude. The optimal intensity, frequency, and duration of exercise to improve obesity and its comorbidities are not fully elucidated. In addition, NEAT is the main determinant of variability in daily energy expenditure, which considerably contributes to weight change in humans. The current evidence regarding NEAT is limited, but NEAT plays an important role for treating obesity. To my knowledge, there are no clinical studies which include "NEAT only" interventions besides volitional physical activity to investigate the effects of NEAT on obesity and metabolic diseases. This is a challenge for the future.
