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Recent studies examining the genetic underpinnings of obesity have suggested that the melanocortin 3 receptor (MC3R) plays a role in body composition and nutrient partitioning (Chen et al., 2000, Demidowich et al., 2017). In mice, inactivating Mc3r causes increased feeding efficiency leading to obesity with increased fat mass, but with reduced lean mass (Chen et al., 2000, Kumar et al., 2009, Butler et al., 2017, Renquist et al., 2011). The common minor human MC3R C17A+G241A haplotype, which leads to 2 amino acid substitutions Thr6Lys and Val81Ile in the protein translated from the first start site of the human gene, leads to a partially inactive protein transcript (Feng et al., 2005). In a large pediatric cohort, individuals homozygous for the MC3R C17A+G241A haplotype were reported to have greater BMI, body fat, plasma leptin, and insulin concentrations, with reduced lean mass when compared to those who were heterozygous (Het) for the C17A + G241A haplotype and homozygous for the wild-type MC3R gene (WT) (Feng et al., 2005). The greater adiposity and reduced signal transduction associated with homozygosity for the C17A+G241A haplotype has since been replicated in other pediatric cohorts (Savastano et al., 2009, Lee et al., 2007, Aris et al., 2015). Supportive data for the effects of this haplotype have also been reported in mice. When the murine Mc3r was replaced with the human MC3R C17A+G241A haplotype, homozygous knockin mice also displayed increased feeding efficiency, greater adiposity, and reduced lean mass (Lee et al., 2016). Among adult human cohorts, however, the MC3R C17A+G241A haplotype has not been associated with greater BMI (Li et al., 2000, Hani et al., 2001, Wong et al., 2002, Rutanen et al., 2007, Calton et al., 2009, Matsuoka et al., 2007) and scant data exist for its effects on other anthropometric or metabolic parameters (Hani et al., 2001, Rutanen et al., 2007). A major limitation of most of these prior studies is the low number of homozygous participants (Calton et al., 2009, Li et al., 2000, Hani et al., 2001, Wong et al., 2002, Rutanen et al., 2007); consequently, many prior conclusions were based largely on the assumption that heterozygotes and homozygotes are phenotypically identical or there would be additive effects from each minor allele/haplotype. Although labelled as a common variant, the MC3R C17A+G241A haplotype is relatively rare in most races and ethnicities, with an estimated prevalence of homozygous individuals between 0.4–3.5% (Obregon et al., 2010, Lee et al., 2007, Rutanen et al., 2007, Hani et al., 2001). Individuals of predominately African ancestry are the exception, as over half carry at least one copy of the haplotype, and 12–16% are homozygous for C17A+G241A (Li et al., 2000, Feng et al., 2005, Savastano et al., 2009). As such individuals have been underrepresented in most adult cohort studies examining MC3R polymorphisms, it remains unclear if homozygous individuals have a different anthropometric and metabolic phenotype than Het or WT adults. To our knowledge, this is the first study of a large cohort of adults that has assessed the association of the MC3R C17A+G241A haplotype with body composition data such as fat mass and lean mass. Our primary hypothesis was that homozygosity for the MC3R C17A+G241A haplotype would be associated with greater BMI and fat mass in African American adults. We additionally hypothesized that this increase in adiposity would be associated with greater insulin resistance and inflammation in homozygous individuals as compared to Het and WT.

Objective Adolescent emotional-eating, referring to eating in response to negative affective states, is frequently reported by those with loss of control (LOC) eating. Although LOC eating has been shown to predict exacerbated disordered eating and excess weight/adiposity gain, the extent to which emotional-eating, either alone or in combination with LOC, predicts adverse outcomes has not been determined. Thus, we examined associations of baseline emotional-eating with changes in disordered eating, BMI, and adiposity over 1-year, and to what degree the presence or absence of baseline LOC moderated these associations. Methods 189 non-treatment-seeking youth (15.4 ± 1.4y; 66% female; 67% non-Hispanic White, 38% overweight [BMI ≥85th %ile]) completed the emotional-eating Scale for Children/Adolescents and the Eating Disorder Examination interview at baseline and again at 1-year. Air displacement plethysmography assessed adiposity at both time points. Results Baseline emotional-eating alone was not significantly associated with the development of objective binge eating or changes in disordered eating attitudes, BMI or adiposity 1-year later. However, baseline emotional-eating interacted with the presence of baseline LOC in the prediction of 1-year outcomes. Among adolescents with LOC eating, greater baseline emotional-eating was related to increased disordered eating attitudes (P = 0.03), BMI (P = 0.04), and adiposity (P = 0.04) at 1-year, after correcting for false discovery rate. Discussion Emotional-eating among youth also reporting LOC was associated with adverse outcomes over 1-year. Adolescents who report both behaviors may represent a subset of individuals at especially high risk for exacerbated disordered eating and excess weight gain. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016)

Summary Background In adults, obesity is associated with abnormalities of thyroid function; there are fewer studies in paediatric cohorts. Objectives To examine associations of weight and adiposity with indices of thyroid function and thyroid-related metabolic factors in children. Design/Methods A sample of 1203 children without obesity (body mass index [BMI]

Summary Background Adults with binge eating disorder may have an exaggerated or blunted cortisol response to stress. Yet, limited data exist among youth who report loss of control (LOC) eating, a developmental precursor to binge eating disorder. Methods We studied cortisol reactivity among 178 healthy adolescents with and without LOC eating. Following a buffet lunch meal adolescents were randomly assigned to watch a neutral or sad film clip. After, they were offered snacks from a multi-item array to assess eating in the absence of hunger. Salivary cortisol was collected at −80, 0, 30 and 50 min relative to film administration, and state mood ratings were reported before and after the film. Results Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps > 0.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps > 0.05). Depressive symptoms and state LOC were related to different aspects of eating behaviour, independent of film condition or cortisol response (ps > 0.05). Conclusions A film clip that induced depressed state affect increased salivary cortisol only in adolescents with more elevated depressive symptoms. Adolescents with and without LOC were differentiated by greater increases in state depressed affect during laboratory test meals but had no difference in cortisol reactivity. Future studies are required to determine if adolescents with LOC manifest alterations in stress reactivity to alternative stress-inducing situations.

Objective Eating in the absence of hunger (EAH) refers to the consumption of palatable foods in a sated state. It has been proposed that EAH promotes excess weight gain in youth; yet, there are limited prospective data to support this hypothesis. We examined whether EAH at baseline predicted increases in body mass (BMI and BMIz) and fat mass (kg) 1 year later among adolescent boys and girls.

Loss of control (LOC) eating refers to the subjective experience of being unable to control what or how much is eaten, regardless of the amount reportedly consumed (1). LOC eating has been well phenotyped, as LOC meals typically are low in protein, high in carbohydrate, and are comprised of highly palatable, energy dense foods (2–4). Pediatric LOC eating is a precursor to partial- and full-syndrome binge eating disorder (BED) and is predictive of exacerbated general and eating disorder psychopathology (5, 6), excessive weight and fat gain (7, 8), and metabolic dysfunction (9). At least one recent episode of LOC eating is reported by 5% to 50% of youth, with higher estimates among adolescent (vs. child), female (vs. male), and overweight (vs. non-overweight) samples (1). LOC eating typically emerges during middle childhood (10) or early adolescence (11, 12). While the presence of a lifetime history of LOC eating has been associated with adverse outcomes (6, 13), only about 50% of youth with LOC eating go on to experience persistent and exacerbated LOC eating patterns during middle to late adolescence and beyond (5, 6, 14). To improve the identification of high-risk youth with LOC eating and refine intervention targets, research is needed to elucidate developmental factors that may contribute to exacerbated disordered eating. Puberty has been identified as a critical risk period for the development of eating disorders and their symptoms, including binge and LOC eating (15). Research on puberty and binge eating lags behind the wealth of data examining the relationship between puberty and other forms of eating disorder psychopathology (15). Pubertal onset, as identified by self-reports of secondary sex characteristics, has been associated with concurrent binge eating among preadolescent girls and boys assessed in the fifth through seventh grades (16, 17). When examining this preadolescent cohort of boys and girls over time, pubertal onset predicted subsequent increases in binge eating frequency (17). Binge eating prevalence was higher at more advanced stages of pubertal development among girls, but not boys, in a large population-based sample, even after accounting for age (18). However, other cross-sectional studies failed to find a significant association between pubertal status and binge eating in girls and boys (19–21). Prior studies’ reliance upon self-report questionnaires to determine both pubertal stage and binge eating severity may have limited reliability and validity relative to interview methods, physical examination, and food intake assessed via laboratory test meals. Moreover, we know of no prior human studies investigating the relationship between pubertal stage and LOC eating. Existing developmental risk models suggest that pubertal development may increase risk for LOC eating through direct and indirect pathways that involve biological and psychosocial factors. Traditional theories posit that the physical changes associated with puberty lead to body dissatisfaction and negative mood, which in turn promote disordered eating behaviors such as classic binge episodes or LOC eating (22, 23). It is hypothesized that girls may be at greater risk for these psychosocial disturbances, as puberty-induced increases in adiposity move girls away from the socially reinforced “thin” body size ideals whereas gains in muscle mass propel boys closer to masculine body ideals (22, 23). Recent theories, by contrast, focus on biological factors and suggest that increases in gonadal hormone levels during puberty play a central role in activating and/or organizing genetic and phenotypic effects that exacerbate disordered eating risk (15). It is also conceivable that pubertal shifts in metabolic hormone levels, which dually regulate eating behaviors and the hypothalamic-pituitary-gonadal axis, may directly promote LOC eating and/or the phenotypic manifestation of LOC eating (24, 25). To date, no known studies have examined the interplay among puberty, LOC eating, and theoretically-driven LOC correlates such as disordered eating attitudes and eating behavior. The current study sought to investigate the association between pubertal development and manifestations of LOC eating in a community sample of children and adolescents. We hypothesized that youth in early-to-mid- and late-pubertal stages would exhibit higher rates of LOC eating than youth in pre-puberty. Based on the mechanisms put forth by psychosocial developmental risk models (22, 23), we hypothesized that associations between LOC eating and concerns about weight and shape would be more robust among post-pubertal youth relative to pre-pubertal youth. Given hypotheses made by biologically-driven developmental risk theories (15), we also expected post-pubertal youth with LOC eating to have greater palatable food consumption in the laboratory, even after adjusting for age and adiposity, relative to pre-pubertal youth with LOC eating and all youth without LOC eating.

Objective To describe the genotypes, phenotypes, immunophenotypes, and treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), a rare autoinflammatory disease, in 5 patients. Methods Clinical information was gathered from medical records and through interviews with 5 patients from 4 kindreds. PSTPIP1 (CD2BP1) exon 10 and exon 11 sequencing was performed in each patient. Neutrophil granule content and cytokine levels were determined in plasma and stimulated peripheral blood mononuclear cells (PBMCs) from patients and controls. Results We identified 2 previously described PAPA syndrome–associated PSTPIP1 mutations, A230T and E250Q, and a novel change, E250K. Disease penetrance was incomplete, with variable expressivity. The cutaneous manifestations included pathergy, cystic acne, and pyoderma gangrenosum. Interleukin-1β (IL-1β) and circulating neutrophil granule enzyme levels were markedly elevated in patients compared to those in controls. PBMC stimulation studies demonstrated impaired production of IL-10 and enhanced production of granulocyte–macrophage colony-stimulating factor. Good resolution of pyoderma gangrenosum was achieved in 3 patients with tumor necrosis factor α (TNFα) blockade treatment. Conclusion This analysis of 5 patients demonstrates that mutations in PSTPIP1 are incompletely penetrant and variably expressed in the PAPA syndrome. Neutrophil granule proteins are markedly elevated ex vivo and in the plasma, and elevated levels might be compatible with a diagnosis of PAPA syndrome. TNFα blockade appears to be effective in treating the cutaneous manifestations of PAPA syndrome.