It is important to underline that although ghrelin increases
It is important to underline that BMS-833923 although ghrelin increases the motivation to eat even in fed state, its effects on food intake and reward are blunted in obese animal models (Zigman et al., 2016). This emphasizes also the interconnection between homeostatic regulation of food intake and reward. The recent discovery of an endogenous GHSR1a antagonist implicated in metabolic control (Ge et al., 2018), suggests new approaches for the study of ghrelin system and food reward [review in (Al-Massadi et al., 2018)]. A better mechanistic understanding of ghrelin signaling in the regulation of food reward behaviors could be crucial for the elucidation of the origin and pathophysiology of food-related diseases including obesity, bulimia, anorexia nervosa or binge-eating disorder.
Conflicts of interest
Acknowledgements: Work in the laboratory of JAG is supported by Inserm, Sorbonne Université (formerly Université Pierre et Marie Curie, UPMC, Paris-6), and grants from ANR MALZ-2013, the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research award (#OSR-2015-CRG4-2602), and Labex Bio-Psy. Work in the laboratory of RN and CD is supported by grants from MINECO (CD BFU2017-87721 and RN: BFU2015-70664R); Xunta de Galicia (RN: 2015-CP080 and 2016-PG057), and Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. O.A-M is funded by the ISCIII/SERGAS through a research contract “Sara Borrell” (CD14/00091). The figures were generated by using materials from Servier Medical Art (Servier) under consideration of a Creative Commons Attribution 3.0 Unported License.
Introduction The cancer anorexia–cachexia syndrome [CACs] is a complex condition aggravating patients with cancer and can often happen in the presence of other conditions such as malnutrition, age related changes in anabolism, comorbidity and physical deconditioning. CACs is a multifactorial syndrome that is characterised by loss of body mass, changes in several metabolic pathways and loss of appetite . It requires a multimodality approach in which the main targets for anticachexia treatments are those factors with an immediate effect on the development and aggravation of cachexia. Body weight depends on energy and nutrient intake and muscle mass on physical activity, and systemic inflammation compromises the body cell mass of major tissues. Thus, anticatabolic therapy should target systemic inflammation (anti-inflammatory); normalize intake of energy and substrates (nutrition support) and increase physical activity (exercise training). Every effort should be undertaken to remove or alleviate all factors disturbing food intake and physical activity (supportive care). The incidence of the syndrome among cancer patients is more than 50% , although it changes by tumor type: in patients with pancreatic or gastric cancer the incidence is more than 80%, whereas is approximately 50% in patients with lung, colon and prostate cancer and around 40% in breast cancer patients . Cancer cachexia represents an important unmet medical need because it adversely affects patients’ quality of life and treatment outcomes. Cachexia in patients with tumors is correlated with significantly impaired survival, most probably due to reduced tolerance to anticancer therapy and augmented susceptibility to other complications . The weight loss often requires dose reductions, treatment delays or definitive termination of treatment, such that weight-losing patients do not obtain the full potential benefit of their cancer therapy .In spite of relevance of these symptoms, treatments are missing . Given the recent findings and the growing interest in the use of anamorelin for the treatment of CACs, in this review we examine the mechanisms of anamorelin, a ghrelin receptor agonist, by which it contrasts catabolic states, its role in regulation of metabolism and energy homeostasis, the data of recent trials in the setting of cancer cachexia and its safety profile.