Winning a won game: caffeine panacea for obesity syndemic.

Over the past decades, chronic sleep reduction and a concurrent development of obesity have been recognized as a common problem in the industrialized world. Among its numerous untoward effects, there is a possibility that insomnia is also a major contributor to obesity. This attribution poses a problem for caffeine, an inexpensive, "natural" agent that is purported to improve a number of conditions and is often indicated in a long-term pharmacotherapy in the context of weight management. The present study used the "common target" approach by exploring the tentative shared molecular networks of insomnia and adiposity. It discusses caffeine targets beyond those associated with adenosine signaling machinery, phosphodiesterases, and calcium release channels. Here, we provide a view suggesting that caffeine could exert some of its effects by acting on several signaling complexes composed of HIF-1α/VEGF/IL-8 along with NO, TNF-α, IL1, and GHRH, among others. Although the relevance of these targets to the reported therapeutic effects of caffeine has remained difficult to assess, the utilization of caffeine efficacies and potencies recommend its repurposing for development of novel therapeutic approaches. Among indications mentioned, are neuroprotective, nootropic, antioxidant, proliferative, anti-fibrotic, and anti-angiogenic that appear under a variety of dissimilar diagnostic labels comorbid with obesity. In the absence of safe and efficacious antiobesity agents, caffeine remains an attractive adjuvant.