PGC-1α and exercise in the control of body weight

Abstract

The increasing prevalence of obesity and its comorbidities represents a major threat to human health globally. Pharmacological treatments exist to achieve weight loss, but the subsequent weight maintenance is prone to fail in the long run. Accordingly, efficient new strategies to persistently control body weight need to be elaborated. Exercise and dietary interventions constitute classical approaches to reduce and maintain body weight, yet people suffering from metabolic diseases are often unwilling or unable to move adequately. The administration of drugs that partially mimic exercise adaptation might circumvent this problem by easing and supporting physical activity. The thermogenic peroxisome proliferator-activated receptor g coactivator 1a (PGC-1a) largely mediates the adaptive response of skeletal muscle to endurance exercise and is a potential target for such interventions. Here, we review the role of PGC-1a in mediating exercise adaptation, coordinating metabolic circuits and enhancing thermogenic capacity in skeletal muscle. We suggest a combination of elevated muscle PGC-1a and exercise as a modified approach for the efficient long-term control of body weight and the treatment of the metabolic syndrome.International Journal of Obesity (2012) 36, 1428 --1435; doi:10.1038/ijo.2012.12; published online 31 January 2012Keywords: PGC-1a; thermogenesis; energy expenditure; exercise; weight control INTRODUCTION Metabolic disorders are increasingly recognized as major threats to public health. Almost two-thirds of the adult Americans are already overweight (body mass index 425 kg m --2 ) and the prevalence will presumably rise in the future. 1 Projections indicate that 86.3% of the adult American population will be overweight and 51.1% will even have to be classified as obese (body mass index 430 kg m --2 ) by the year 2030. 2 Importantly, excessive body weight fosters the development of comorbidities such as hypertension, dyslipidemia, cancer, cardiovascular disease and diabetes. 3,4 A protracted energy imbalance where energy intake exceeds expenditure is considered as a key element in the etiology of metabolic impairments. 5,6 Reducing energy intake (by nutritional intervention), increasing energy expenditure (by physical activity) or the combination of both thus constitute cornerstones in the treatment of metabolic disorders. 7 Such lifestyle interventions generally lead to weight loss initially 7 and improve metabolic parameters, 8 but the majority of patients regain their weight in the long run. 9,10 A meta-analysis of studies published between 1931 and 1999 reveals a median success rate to maintain body weight after weight loss of a moderate 15%. 11 This impressive recidivism rate after otherwise successful weight loss is partially due to poor adherence to lifestyle interventions and potently facilitated by coordinate actions of ancestral physiological responses designed to powerfully defend and restore body energy stores. 12 Indeed, weight loss initiated by reduced energy intake rapidly turns on a 'thrift...

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Effect of novel dietary supplement on metabolism in vitro and in vivo

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PGC-1α Improves Glucose Homeostasis in Skeletal Muscle in an Activity-Dependent Manner

“…People suffering from metabolic disorders often are unable or unwilling to achieve the levels of physical activity that are required to elicit health benefits. The auxiliary use of substances that mimic the plastic adaptations to exercise, so-called exercise mimetics (8), constitutes a seemingly attractive therapeutic approach to ease and support physical activity or amplify the effects of exercise, at least when potential drawbacks and limitations are ignored (9,10). As a key regulator of muscle plasticity (11,12), the peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α) constitutes a potential target for such drugs (13).…”