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.

Use of an adult rat retinal explant model for screening of potential retinal ganglion cell neuroprotective therapies.

PURPOSE. To validate an established adult organotypic retinal explant culture system for use as an efficient medium-throughput screening tool to investigate novel retinal ganglion cell (RGC) neuroprotective therapies. METHODS. Optimal culture conditions for detecting RGC neuroprotection in rat retinal explants were identified. Retinal explants were treated with various recognized, or purported, neuroprotective agents and cultured for either 4 or 7 days ex vivo. The number of cells surviving in the RGC layer (RGCL) was quantified using histologic and immunohistochemical techniques, and statistical analyses were applied to detect neuroprotective effects. RESULTS. The ability to replicate previously reported in vivo RGC neuroprotection in retinal explants was verified by demonstrating that caspase inhibition, brain-derived neurotrophic factor treatment, and stem cell transplantation all reduced RGCL cell loss in this model. Further screening of potential neuroprotective pharmacologic agents demonstrated that betaxolol, losartan, tafluprost, and simvastatin all alleviated RGCL cell loss in retinal explants, supporting previous reports. However, treatment with brimonidine did not protect RGCL neurons from death in retinal explant cultures. Explants cultured for 4 days ex vivo proved most sensitive for detecting neuroprotection. CONCLUSIONS. The current adult rat retinal explant culture model offers advantages over other models for screening potential neuroprotective drugs, including maintenance of neurons in situ, control of environmental conditions, and dissociation from other factors such as intraocular pressure. Verification that neuroprotection by previously identified RGC-protective therapies could be replicated in adult retinal explant cultures suggests that this model could be used for efficient medium-throughput screening of novel neuroprotective therapies for retinal neurodegenerative disease.