See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/318840523 Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder: shedding light on the darkness Article in Journal of Neurogenetics · August 2017 DOI: 10.1080/01677063.2017.1353092 CITATIONS READS 3 760 4 authors, including: Claude Everaerts Leticia G León French National Centre for Scientific Research Erasmus MC 89 PUBLICATIONS 920 CITATIONS 144 PUBLICATIONS 1,584 CITATIONS SEE PROFILE SEE PROFILE Angel Acebes Universidad de La Laguna 45 PUBLICATIONS 871 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: DIAMANTE View project Novel Antiproliferative Drugs View project All content following this page was uploaded by Leticia G León on 30 October 2017. The user has requested enhancement of the downloaded file. Journal of Neurogenetics ISSN: 0167-7063 (Print) 1563-5260 (Online) Journal homepage: http://www.tandfonline.com/loi/ineg20 Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder: shedding light on the darkness Germán Cuesto, Claude Everaerts, Leticia G. León & Angel Acebes To cite this article: Germán Cuesto, Claude Everaerts, Leticia G. León & Angel Acebes (2017): Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder: shedding light on the darkness, Journal of Neurogenetics To link to this article: http://dx.doi.org/10.1080/01677063.2017.1353092 Published online: 01 Aug 2017. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ineg20 Download by: [University of La Laguna Vicerrectorado] Date: 01 August 2017, At: 07:00 JOURNAL OF NEUROGENETICS, 2017 https://doi.org/10.1080/01677063.2017.1353092 REVIEW ARTICLE Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder: shedding light on the darkness German Cuestoa, Claude Everaertsb, Leticia G. Leon c and Angel Acebesa aCentre for Biomedical Research of the Canary Islands, Institute of Biomedical Technologies, University of La Laguna, Tenerife, Spain; bCentre des Sciences du Gout^ et de l'Alimentation, UMR 6265 CNRS, UMR 1324 INRA, Universite de Bourgogne Franche-Comte, Dijon, France; cCancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, Pisa, Italy ABSTRACT ARTICLE HISTORY Eating-disorders (EDs) consequences to human health are devastating, involving social, mental, emo- Received 9 May 2017 tional, physical and life-threatening aspects, concluding on impairment and death in cases of extreme Revised 26 June 2017 anorexia nervosa. It also implies that people suffering an ED need to find psychiatric and psychological Accepted 5 July 2017 help as soon as possible to achieve a fully physical and emotional recovery. Unfortunately, to date, there is a crucial lack of efficient clinical treatment to these disorders. In this review, we present an KEYWORDS overview concerning the actual pharmacological and psychological treatments, the knowledge of cells, Eating disorders; circuits, neuropeptides, neuromodulators and hormones in the human brain- and other organs- under- pharmacology; neuromodu- lying these disorders, the studies in animal models and, finally, the genetic approaches devoted to face lators; genetic approaches this challenge. We will also discuss the need for new perspectives, avenues and strategies to be devel- oped in order to pave the way to novel and more efficient therapeutics. Introduction carbohydrates and fat food are consumed in a very short- time period, followed by 1 or more compensatory purge Eating-disorders (EDs) as anorexia nervosa (AN), bulimia behaviours (vomiting, laxatives, fasting, etc … ). That takes nervosa (BN) and binge-eating disorder (BED), have both a place on average a minimum of twice weekly for three or deep social impact and an enormous cost to public health- more months, or, in extreme cases, several times a day. BN care systems (Keski-Rahkonen & Mustelin, 2016). The is divided into two subtypes: the above-mentioned purging- example of Europe is extremely illustrative: besides a very type and the lesser-common non-purging type, characterised high risk of premature mortality, more than 2/3 of those EDs patients had at least some role impairment in at least by fasting or excessive exercise trying to compensate for the one domain (Preti et al., 2009). In fact, the prevalence of calories obtained from the previous binge. Besides, there EDs has increased across time, particularly in the second exist comorbidities between BN and other disorders as sub- half of the twentieth century (Bulik et al., 2006). In the USA, stance abuse, affective disorders, and attention disorders 20 million women and 10 million men had suffered from a (Altman & Shankman, 2009; Hatsukami, Eckert, Mitchell, & clinically significant ED at some time in their life Pyle, 1984). Finally, Binge eating disorder (BED) patients (Samnaliev, Noh, Sonneville, & Austin, 2015) with 7300 show also repetitive and uncontrolled episodes of over con- worldwide deaths in 2010 (Lozano et al., 2012) resulting in sumption of larger amounts of food in a discrete period, but, 6 Downloaded by [University of La Laguna Vicerrectorado] at 07:00 01 August 2017 2.2 Â 10 disability-adjusted life years (DALYs) (Murray unlike BN and AN they do not show recurrent compensa- et al., 2012). tory purging, fasting and excessive exercise behaviours Anorexia nervosa is defined as an association of an (American Psychiatric Association, 2013). As for AN and abnormally low body weight, an intense fear of gaining BN, BED has been associated with medical and psychiatric weight and a distorted cognition regarding weight, shape, comorbidities, as mood (anxiety) and substance use disor- and drive for thinness. AN is a disorder but also a symptom ders (Becker & Grilo, 2015). Interestingly, BED is the most of other disorders, as depression, bipolar disorder, anxiety prevalent among all eating disorders, being higher in women disorders (obsessive–compulsive disorder, panic disorder, than in men, and also the most underdiagnosed and under- social phobias, and post-traumatic stress disorder) and sub- treated, due to insufficient diagnostic criteria and lack of stance abuse (O’Brien & Vincent, 2003; Woodside & Staab, available treatment options [see Section 2 below and also 2006). In turn, BN is characterized by episodes of binge eat- Kornstein, Kunovac, Herman, & Culpepper (2016)]. ing – defined itself as ‘recurrent periods of uncontrolled Eating-disorders have been long considered as severe psy- overeating’–in which big amounts of high-sugar, chiatric disorders of unknown aetiology. As previously CONTACT Angel Acebes [email protected] Centre for Biomedical Research of the Canary Islands, Institute of Biomedical Technologies, Department of Basic Medical Sciences, Faculty of Medicine, University of La Laguna, 38071 La Laguna, Tenerife, Spain; Leticia G. Leon [email protected] Cancer Pharmacology Lab, University of Pisa, Ospedale di Cisanello, Edificio 6, via Paradisa, 2. 56124 Pisa, Italy ß 2017 Informa UK Limited, trading as Taylor & Francis Group 2 GERMAN CUESTO ET AL. mentioned, BN and BED are closely related to affective, Seeley, Porte, & Schwartz, 1998). Single neuropeptides con- attention, emotional and mood disorders. Social cognition tribute to feeding behaviours in mammals (Dailey & encompass the psychological processes endowing individuals Bartness, 2009), and their roles in the neuronal circuits to observe, process, store and retrieve information obtained underlying these behaviours have been intensively studied. from conspecifics in social interactions (Frith, 2008). Poor NPY/AgRP peptidergic neurons increase feeding intake by recognition of emotions in others is documented in AN inhibiting POMC/CART system which stimulates anorexi- patients and facial emotion recognition difficulties persist in genic neurons in the lateral hypothalamus (LH) area, and them even after recovery (Oldershaw et al., 2011). Besides, stimulating orexigenic neurons in the paraventricular nucleus brain abnormalities have been described in AN patients, (PVN) (Aponte, Atasoy, & Sternson, 2011; Atasoy, Betley, including abnormal neural activation (Uher et al., 2004) and Su, & Sternson, 2012; Wu, Boyle, & Palmiter, 2009). altered neurotransmitter function (Kaye, Fudge, & Paulus, Together, these neuropeptides translates the feeding behav- 2009). More research is crucial to establish links between iour in appetite as well as adaptive responses (Borgland social cognition abnormalities and neurological defaults asso- et al., 2009). ciated with AN (Cardi et al., 2015). Interestingly, several pieces of evidence indicate that Under these grounds, deciphering unambiguously how neurobiological mechanisms underlying ED might involve an the brain controls food intake and satiation mechanisms is overreaction of the immune system, generating, in turn, a crucial to know how eating-associated pathological disorders dysfunction of neuropeptide signalling. Thus, reactive are bypassing this control. To date, there is a good know- Immunoglobulins (Igs) bind to food-intake neuropeptides ledge about the bidirectional communication among exten- (named peptide autoantibodies) and are identified in the sive areas of the nervous system (including the cortex, basal serum of AN/BN patients, predominantly bound to a-MSH ganglia, and the limbic system)