Obesity wars: may the smell be with you

Classically, the regulation of energy balance has been based on central and peripheral mechanisms sensing energy, nutrients, metabolites, and hormonal cues. Several cellular mechanisms at central level, such as hypothalamic AMP-activated protein kinase (AMPK), integrate this information to elicit counterregulatory responses that control feeding, energy expenditure, and glucose homeostasis, among other processes. Recent data have added more complexity to the homeostatic regulation of metabolism by introducing, for example, the key role of "traditional" senses and sensorial information in this complicated network. In this regard, current evidence is showing that olfaction plays a key and bidirectional role in energy homeostasis. Although nutritional status dynamically and profoundly impacts olfactory sensitivity, the sense of smell is involved in food appreciation and selection, as well as in brown adipose tissue (BAT) thermogenesis and substrate utilization, with some newly described actors, such as olfactomedin 2 (OLFM2), likely playing a major role. Thus, olfactory inputs are contributing to the regulation of both sides of the energy balance equation, namely, feeding and energy expenditure (EE), as well as whole body metabolism. Here, we will review the current knowledge and advances about the role of olfaction in the regulation of energy homeostasis.