Seeking satiety: From signals to solutions

Abstract

Remedies for the treatment of obesity date to Hippocrates, when patients with obesity were directed to “reduce food and avoid drinking to fullness” and begin “running during the night.” Similar recommendations have been repeated ever since, despite the fact that they are largely ineffective. Recently, highly effective therapeutics were developed that may soon enable physicians to manage body weight in patients with obesity in a manner similar to the way that blood pressure is controlled in patients with hypertension. These medicines have grown out of a revolution in our understanding of the molecular and neural control of appetite and body weight, reviewed here.

Perspective: Do Scientists Become Part of the Obesity Problem?

“…Today, obesity is primarily approached using a conceptual framework of endogenous causes, relating to the neurobiology of appetite control and energy balance dysregulation [3]. Consequently, research is directed to pharmacological solutions as an adjunct to lifestyle interventions [2][3][4], which have led us to the Y of the road suggesting that treatment of patients is a solution of the population-wide obesity issue.…”

“…Although population-wide obesity is a public health issue, with implications for planetary sustainability [1], its solution is still widely regarded as a biomedical issue [2]. Accordingly, the wide-spread acceptance of new anti-obesity drugs may suggest that we should accept the epidemic and drug-treat it, not fight it [3]. Presently, there are different perceptions of obesity itself: looking at the same phenomenon, protagonists of biomedicine consider obesity as a disease, where effective therapeutics for obesity management are needed [2][3][4] whereas public health scientists see increasing fatness as the result of a normal response, by normal people, to an abnormal unhealthy environment, and where structural and political strategies may add to solutions [5].…”

“…Accordingly, the wide-spread acceptance of new anti-obesity drugs may suggest that we should accept the epidemic and drug-treat it, not fight it [3]. Presently, there are different perceptions of obesity itself: looking at the same phenomenon, protagonists of biomedicine consider obesity as a disease, where effective therapeutics for obesity management are needed [2][3][4] whereas public health scientists see increasing fatness as the result of a normal response, by normal people, to an abnormal unhealthy environment, and where structural and political strategies may add to solutions [5]. Since biomedical and the public health experts may have lost sight of each other we feel that they are at risk to become part of the obesity problem.…”

Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes

“…Likewise, while ghrelin has the potential to be a useful treatment for cancer cachexia [ 14 ], strategies for inhibiting ghrelin signaling have thus far not produced viable pharmacotherapies for obesity, but this is an ongoing area of research [ 15 , 16 ]. Leptin and ghrelin are only two of many neuroendocrine signaling pathways facilitating peripheral-brain communication regulating metabolism [ 17 , 18 ]. The obvious question was whether leveraging any one or a combination of these other signaling pathways may provide a more successful path to obesity pharmacotherapy.…”