Obesity reflects an imbalance between food (energy) intake and exercise (energy) output. Regulation of this whole-body energy homeostasis relies on an intricate balance between food intake and energy expenditure. This balance requires the coordinated response of peripheral and central neuronal inputs –– including hormones, multiple peptides, and neurotransmitters. These peripheral factors include leptin, insulin, ghrelin, glucagon-like peptide-1 (GLP-1), insulin-like growth factor-1 (IGF1), and cholecystokinin.
In order to adapt quickly to variations in environmental conditions and maintain whole-body homeostasis, mammalian systems have developed neuronal circuits within the central nervous system (CNS) that integrate internal cues into autonomic responses via the sympathetic nervous system and parasympathetic nervous system. The CNS is responsible for coordinating these autonomic systems to control many vital physiological functions –– such as pancreatic secretion, lipid storage, thermogenesis, peripheral glucose uptake, and liver glucose flux.
Variations in autonomic tone are orchestrated by extensive (and often reciprocal) connections between the hypothalamus and brainstem nuclei. In the hypothalamus, the melanocortin system in the arcuate nucleus controls feeding in response to circulating insulin and leptin levels. Leptin promotes energy expenditure by way of increasing sympathetic nerve activity and subsequent catecholamine signaling in white adipose tissue (WAT) and brown adipose tissue (BAT), to promote lipid breakdown and fatty acid oxidation. Additionally, cold stimulation, or pharmacological activation of the b-adrenergic pathway, enhances formation of brown-like or beige adipocytes predominantly in WAT of rodents, which are characterized by a thermogenic gene expression program similar to that BAT, which includes high level expression of mitochondrial-uncoupling protein-1.
Smells (olfactory inputs from the nose) help coordinate food appreciation and selection, but their role in systemic physiology and energy balance is poorly understood. In the attached article, authors determine that mice, upon conditional removal of mature olfactory sensory neurons (OSNs), were resistant to diet-induced obesity, accompanied by increased thermogenesis in BAT depots. Acute loss of smell perception after obesity onset –– not only nullified further weight gain, but also improved fat mass and insulin resistance. Diminished olfactory input stimulated sympathetic nerve activity, resulting in activation of b-adrenergic receptors in WAT and BAT to promote lipolysis (lipid breakdown). Conversely, conditional blockade of the IGF1 receptor in OSNs enhanced olfactory performance in mice –– resulting in amplified obesity and insulin resistance. These intriguing data in mice reveal a new bidirectional function for the olfactory system in controlling energy homeostasis in response to sensory and hormonal signals. Does the same thing happen in humans?
Cell Metab 2o17; 26: 198–211