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Background A chronic imbalance of energy intake and energy expenditure results in excess fat storage. The obesity often caused by this overweight is detrimental to the health of millions of people. Understanding both sides of the energy balance equation and their counter-regulatory mechanisms is critical to the development of effective therapies to treat this epidemic. Scope of review Behaviors surrounding ingestion have been reviewed extensively. This review focuses more specifically on energy expenditure regarding bodyweight control, with a particular emphasis on the organs and attractive metabolic processes known to reduce bodyweight. Moreover, previous and current attempts at anti-obesity strategies focusing on energy expenditure are highlighted. Precise measurements of energy expenditure, which consist of cellular, animal, and human models, as well as measurements of their translatability, are required to provide the most effective therapies. Major conclusions A precise understanding of the components surrounding energy expenditure, including tailored approaches based on genetic, biomarker, or physical characteristics, must be integrated into future anti-obesity treatments. Further comprehensive investigations are required to define suitable treatments, especially because the complex nature of the human perspective remains poorly understood., Molecular Metabolism, 51

Humans have inherited complex neural circuits which drive behavioral, somatic, and autonomic thermoregulatory responses to defend their body temperature. While they are well adapted to dissipate heat in warm climates, they have a reduced capacity to preserve it in cold environments. Consequently, heat production is critical to defending their core temperature. As in other large mammals, skeletal muscles are the primary source of heat production recruited in cold-exposed humans. This is achieved voluntarily in the form of contractions from exercising muscles or involuntarily in the form of contractions from shivering muscles and the recruitment of nonshivering mechanisms. This review describes our current understanding of shivering and nonshivering thermogenesis in skeletal muscles, from the neural circuitry driving their recruitment to the metabolic substrates that fuel them. The presence of these heat-producing mechanisms can be measured in vivo by combining indirect respiratory calorimetry with electromyography or biomedical imaging modalities. Indeed, much of what is known regarding shivering in humans and other animal models stems from studies performed using these methods combined with in situ and in vivo neurologic techniques. More recent investigations have focused on understanding the metabolic processes that produce the heat from both contracting and noncontracting mechanisms. With the growing interest in the potential therapeutic benefits of shivering and nonshivering skeletal muscle to counter the effects of neuromuscular, cardiovascular, and metabolic diseases, we expect this field to continue its growth in the coming years.