Energy cost of physical activity in patients with anorexia nervosa

To assess the amount of energy cost for a standardized physical activity, activity‐induced thermogenesis (AIT) was measured in eight hyperactive and eight sedentary patients with anorexia nervosa as well as in 14 sport students and 14 sedentary controls. Resting metabolic rate (RMR) and AIT were measured by indirect calorimetry. RMR was measured after an overnight fast and began 20 min after the placement of the hood and lasted for 20 min. For the next 10 min subjects had to ride a recumbent bicycle ergometer (25 W) and AIT was measured. Absolute RMR in both anorectic groups was significantly lower than in both normal weight groups, but after adjusting for lean body mass (LBM) RMR did not differ among the groups. Absolute AIT was significantly lower in hyperactive anorectic patients and in sport students compared to the controls. After adjusting for LBM AIT was still significantly lower in the hyperactive anorectic group and in the group of sport students compared to the control group. These results indicate that despite severe underweight and biological changes in muscles anorectic patients still have an energy sparing metabolism during moderate physical activity. Copyright © 2000 John Wiley & Sons, Ltd and Eating Disorders Association.     

Peroxisome proliferator-activated receptor δ (PPARδ), a novel target site for drug discovery in metabolic syndrome

The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)α and γ agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARδ functions is lagging behind because specific PPARδ agonists have not been developed. The appearance of new PPARδ agonists is brightening the prospects for elucidating the physiological role of PPARδ. PPARδ is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARδ agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARδ agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARδ may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARδ agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARδ itself and its agonists in the future.     

Reciprocal Compensation to Changes in Dietary Intake and Energy Expenditure within the Concept of Energy Balance

An imbalance between energy intake and energy expenditure is the primary etiology for excess weight gain. Increased energy expenditure via exercise and energy restriction via diet are commonly used approaches to induce weight loss. Such behavioral interventions, however, have generally resulted in a smaller than expected weight loss, which in part has been attributed to compensatory adaptations in other components contributing to energy balance. Current research points to a loose coupling between energy intake and energy expenditure on a daily basis, and evidence for long-term adaptations has been inconsistent. The lack of conclusive evidence on compensatory adaptations in response to alterations in energy balance can be attributed to differences in intervention type and study population. Physical activity (PA) levels may be reduced in response to aerobic exercise but not in response to resistance exercise. Furthermore, athletic and lean adults have been shown to increase their energy intake in response to exercise, whereas no such response was observed in obese adults. There is also evidence that caloric restriction is associated with a decline in PA. Generally, humans seem to be better equipped to defend against weight loss than avoid weight gain, but results also show a large individual variability. Therefore, individual differences rather than group means should be explored to identify specific characteristics of “compensators” and “noncompensators.” This review emphasizes the need for more research with simultaneous measurements of all major components contributing to energy balance to enhance the understanding of the regulation of energy balance, which is crucial to address the current obesity epidemic.     

Uncoupling of sarcoplasmic reticulum Ca²⁺-ATPase by N-arachidonoyl dopamine. Members of the endocannabinoid family as thermogenic drugs

BACKGROUND AND PURPOSE

The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) plays a role in thermogenesis. The exogenous compound capsaicin increased SERCA-mediated ATP hydrolysis not coupled to Ca²⁺ transport. Here, we have sought to identify endogenous compounds that may function as SERCA uncoupling agents.

EXPERIMENTAL APPROACH

Using isolated SR vesicles from rabbits, we have screened for endogenous compounds that uncouple SERCA. We have also studied their ability to deplete cytoplasmic ATP from human skeletal muscle cells in culture.

KEY RESULTS

Studies on SR vesicles showed that the endogenous lipid metabolite N-arachidonoyl dopamine (NADA) was a potent stimulator of SERCA uncoupling. NADA stabilized an E₁-like pump conformation that had a lower dephosphorylation rate, low affinity for Ca²⁺ at the luminal sites and a specific proteinase K cleavage pattern involving protection of the C-terminal p83C fragment from further cleavage. Moreover, we found a significantly decreased cytoplasmic ATP levels following treatment of skeletal muscle cells with 100 nM NADA. This effect was dependent on the presence of glucose and abolished by pretreatment with the specific SERCA inhibitor thapsigargin, regardless of the presence of glucose.

CONCLUSIONS AND IMPLICATIONS

NADA is an endogenous molecule that may function as SERCA uncoupling agent in vivo. Members of the endocannabinoid family exert concerted actions on several Ca²⁺-handling proteins. Uncoupling of SERCA by exogenous compounds could be a novel post-mitochondrial strategy for reduction of cellular ATP levels. In addition, signalling networks leading to SERCA uncoupling can be explored to study the importance of this ion pump in pathophysiological conditions related to metabolism.     

Daily physical activity and type 2 diabetes: A review

Physical activity improves glycemic control and reduces the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes (T2D). Moderate to vigorous physical activity is recommended to manage T2D; however, patients with T2D can be physically weak, making it difficult to engage in the recommended levels of physical activity. Daily physical activity includes various activities performed during both occupational and leisure time such as walking, gardening, and housework that type 2 diabetic patients should be able to perform without considerable physical burden. This review focuses on the association between daily physical activity and T2D. Walking was the most common form of daily physical activity, with numerous studies demonstrating its beneficial effects on reducing the risk of T2D, CVD, and mortality. Walking for at least 30 min per day was shown to reduce the risk of T2D by approximately 50%. Additionally, walking was associated with a reduction in mortality. In contrast, evidence was extremely limited regarding other daily physical activities such as gardening and housework in patients with T2D. Recent studies have suggested daily physical activity, including non-exercise activity thermogenesis, to be favorably associated with metabolic risks and mortality. However, well-designed longitudinal studies are warranted to elucidate its effects on overall health.