Diet-induced disruption of the olfactory system: not only obesity is to blame.

Abstract

Most animals have an olfactory system (OS) whose anatomy, organization and functioning are remarkably similar. The OS is responsible for the sense of smell, through which animals gather information about the chemical composition of the environment (Manzini et al. 2022). In most species, the sense of smell conveys essential information for finding suitable food, avoiding predators, orienting themselves in space and increasing reproductive success. This also applies to humans, where it is crucial for the enjoyment of food and strongly influences general well-being (Boesveldt & Parma, 2021). The OS also senses and responds to endogenous signals that change depending on the metabolic status. The activation of receptors expressed in cells of the OS by specific hormones and nutritional signalling molecules can influence the functioning of the OS and thus modulate the sense of smell (Fadool & Kolling, 2020). It has long been known that obesity, that is, an excessive body fat accumulation, negatively affects our health and leads to a progressive decline of several organ systems (Tchernof & Després, 2013). More recent studies have linked obesity to cellular and molecular disruption of the OS. It has been reported that obese animals have both a smaller number of olfactory sensory neurons (OSNs) and associated projections to the olfactory bulb (OB), reduced expression of olfactory receptors, lesser amounts of olfactory G-proteins and weaker odorant-induced receptor potentials. On the level of the OB, the first relay centre of the OS, obesity alters the functioning of projection neurons, neurons that transmit olfactory information to higher olfactory centres. Together, this leads to an impaired sense of smell (Fadool & Kolling, 2020). The apparent link between obesity and the alterations of the OS has been challenged by ground-breaking results obtained using transgenic mouse lines. While genetically obese animals that consumed a nutrient-balanced diet retained an intact OS, animals genetically resistant to obesity still exhibited a reduction of OSNs when fed a diet containing a higher amount of fat. These results led to the hypothesis that excess fat in the diet rather than obesity could trigger alterations of the OS (Fadool & Kolling, 2020). In the current issue of The Journal of Physiology, Chelette and coworkers (2022) have examined this hypothesis in detail and provided compelling evidence that excess fat in the diet rather than the development of obesity is the cause for loss of OSNs and associated projections to the OB. To decouple diet-induced obesity from dietary fat consumption, the authors developed a sophisticated pair-feeding method that allowed feeding a moderately high-fat (MHF) diet while keeping the total calories the same as in a nutrient-balanced (but lower fat) control diet. Using this feeding method and a transgenic mouse line in which a specific subpopulation of OSNs can be readily visualized, the authors elegantly demonstrated the following main points: