Supplementary Material for: Rapid emergence of appetite and hunger resulting in weight gain and improvement of eating disorder symptomatology during and after short-term off-label metreleptin treatment of a patient with anorexia nervosa

Off-label treatment of a 15-year-old female patient with anorexia nervosa with human recombinant leptin (metreleptin) for nine days was associated with self-reported increments of appetite and hunger resulting in rapid weight gain, substantial improvement of eating disorder cognitions and of depression. The results further substantiate the effects of metreleptin on both AN and depression. We contrast these results with the widespread view that leptin is an anorexigenic hormone. Randomized controlled trials are warranted to confirm the described effects

Erratum: Variations in the Prevalence of Obesity Among European Countries, and a Consideration of Possible Causes

Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the ‘Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe

Supplementary Material for: The Effect of SH2B1 Variants on Expression of Leptin- and Insulin-Induced Pathways in Murine Hypothalamus

<p><b><i>Objective: </i></b>We aimed to determine the effect of human <i>SH2B1</i> variants on leptin and insulin signaling, which are major regulators of energy homeostasis, on the RNA level. <b><i>Methods:</i></b> We analyzed the expression of infrequent alleles of seven <i>SH2B1</i> variants (Arg67Cys, Lys150Arg, Thr175Ala, Thr343Met, Thr484Ala, Ser616Pro, and Pro689Leu) in response to insulin or leptin cell stimulation. Two of these were identified in own mutation screens, the others were predicted to be deleterious or to serve as controls. The variants were analyzed in a homologous system of mouse hypothalamic cells. Changes in expression of downstream genes were measured. Student's t-test for independent samples was applied, and effect sizes using Cohen's d with 95% confidence intervals were therefore calculated. <b><i>Results:</i></b> In 34 of 54 analyzed genes involved in leptin (JAK/STAT or AKT) signaling, variants nominally changed expression. The expression of three genes was considerably increased <i>(</i>p values ≤ 0.001: <i>Gbp2b</i> (67Cys; <i>d</i> = 25.11 (-3.53, -2.70)), <i>Irf9</i> (689Leu; <i>d</i> = 44.65 (-2.57, -2.26)), and <i>Isg15</i> (150Arg; <i>d</i> = 20.35 (-2.19, -1.57))). Of 32 analyzed genes in the insulin signaling pathway, the expression of 10 genes nominally changed (p ≤ 0.05), three resulted in p values ≤ 0.01 (<i>Cap1</i> (150Arg; <i>d</i> = 7.48 (-0.62, -0.24)), <i>Mapk1</i> (343Met; <i>d</i> = -6.80 (0.17, 0.45)), and <i>Sorbs1</i> (689Leu; <i>d</i> = 7.82 (-1.60, -0.64))). <b><i>Conclusion:</i></b> The increased expression of genes in the leptin (JAK/STAT or AKT) signaling pathway implies that the main mode of action for human <i>SH2B1</i> mutations might affect leptin signaling rather than insulin signaling.</p