Francesca Pescatore

Stresses like low nutrients, systemic inflammation, cancer or infections provoke a catabolic state characterized by enhanced muscle proteolysis and amino acid release to sustain liver gluconeogenesis and tissue protein synthesis. These conditions activate the family of Forkhead Box (Fox) O transcription factors. Here we report that muscle-specific deletion of FoxO members protects from muscle loss as a result of the role of FoxOs in the induction of autophagy-lysosome and ubiquitin-proteasome systems. Notably, in the setting of low nutrient signalling, we demonstrate that FoxOs are required for Akt activity but not for mTOR signalling. FoxOs control several stress-response pathways such as the unfolded protein response, ROS detoxification, DNA repair and translation. Finally, we identify FoxO-dependent ubiquitin ligases including MUSA1 and a previously uncharacterised ligase termed SMART (Specific of Muscle Atrophy and Regulated by Transcription). Our findings underscore the central function of FoxOs in coordinating a variety of stress-response genes during catabolic conditions.

Abstract Background and aims The concept of "Food Addiction" has been based on criteria of Substance Use Disorder. Several studies suggested a relationship between food addiction and eating disorders, but little is known about its extent or role. We aim at exploring if food addiction is coincident with a specific eating disorder (binge eating disorder appears the closest) or it is a separate diagnostic entity that afflicts in comorbidity with eating disorders or other conditions like obesity or even in the general population. Methods This systematic review and meta-analysis analyzed observational studies with a comparative estimation on rates of subjects affected by binge eating disorder and food addiction. Results Binge eating disorder shows higher comorbidity with food addiction compared to other eating disorders (OR = 1.33, 95% CI, 0.64–2.76; c 2 = 4.42; p = 0.44;I 2 = 0%), or each eating disorder [anorexia nervosa purging type (OR = 1.93, 95% CI, 0.20–18.92; p = 0.57) and restrictive type (OR = 8.75, 95% CI, 1.08–70.70; p = 0.04)], obese patients (OR = 5.72, 95% CI, 3.25–10.09; p = < 0.0001) and individuals from the general population (OR = 55.41, 95% CI, 8.16–376.10; c 2 = 18.50; p < 0.0001; I 2 = 0%)but has decreased prevalence when compared to bulimia nervosa (OR = 0.85, 95% CI, 0.33–2.22; c 2 = 0.35; p = 0.74; I 2 = 0%). Discussion and conclusions Our data show that the prevalence of food addiction in binge eating disorder is higher than in other eating disorders except in bulimia nervosa. Moreover, it is a separate diagnostic reality and can be detected in people without mental illness and in the general population. Food addiction might have a prognostic value, since in comorbidity, and should be addressed to boost treatment efficacy and patient’s recovery. Level of evidence I: Evidence obtained systematic reviews and meta-analyses.