SUMMARY Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARγ and C/EBPα . Here we demonstrate that the IRE1α-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1α knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPβ, a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1α is required as only the spliced form of XBP1 (XBP1s) rescues the adipogenic defect exhibited by XBP1-deficient cells. Taken together, our data show that the IRE1α-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis.

Objective Poorer executive function (EF) has been linked to disinhibited eating in youth, suggesting poor EF predisposes toward obesity, yet the specific nature and extent of interconnections between facets of these domains is unclear. Network analysis provides a promising framework for elucidating the relationship between poor EF and disinhibited eating, and offers insights into potential maintenance processes. Method Among youth ages 8–17 years, a regularized partial correlation network of EF and disinhibited eating facets was estimated to examine expected influence centrality and bridge expected influence. Computerized neurocognitive tasks assessed EF variables, including decision‐making, general and food‐related inhibitory control, delayed gratification, cognitive flexibility, and working memory. Disinhibited eating variables included total carbohydrate–fat intake at a laboratory test meal and self‐reported eating in the absence of hunger, emotional eating, and loss‐of‐control eating severity. Results In the current sample (N = 248; Mage = 12.5; 54.8% female; 43.5% non‐Hispanic White; 25.8% non‐Hispanic Black; BMI %ile = 65.8 ± 27.8), emotional eating in response to depressive symptoms emerged as a central symptom in the network. Carbohydrate–fat intake had the highest bridge expected influence and was most strongly connected to general inhibitory control (part r = .14). Discussion The link between general inhibitory control and objective palatable food intake may be particularly salient in maintaining maladaptive eating behavior. Interventions targeting behavioral disinhibition may disrupt associations among a network of disinhibited eating facets in youth and should be targets for longitudinal research.

ObjectiveBeyond sleep duration, other facets of sleep such as variability and timing may be associated with obesity risk in youth. However, data are limited. Using a longitudinal design, this study tested whether multiple facets of sleep were associated with fat mass gain over 1 year.MethodsA convenience sample of non‐treatment‐seeking youth (age 8‐17 years) wore actigraphy monitors for 14 days. Average weekly sleep duration, within‐person sleep duration variability, weekend catch‐up sleep, bedtime and wake time shift, social jet lag, bedtime, wake time, and sleep midpoint were calculated. The association of each facet of baseline sleep with 1‐year fat mass, adjusting for baseline fat mass and height, was examined.ResultsA total of 137 youths (54.0% female; mean [SD], age 12.5 [2.6] years; 28.4% non‐Hispanic Black or African American; baseline fat mass = 15.3 [8.9] kg; 1‐year fat mass = 17.0 [10.0] kg; 28.5% with baseline overweight or obesity) were studied. Wake time (p = 0.03) and sleep midpoint (p = 0.02) were inversely associated with 1‐year fat mass, such that earlier wake time and midpoint were associated with higher 1‐year fat mass. No other facet of sleep was significantly associated with 1‐year fat mass (p > 0.09).ConclusionsUsing objective measures, youth with earlier wake times and sleep midpoints had greater gains in fat mass. Additional research is needed to determine whether sleep timing may be a modifiable target to prevent pediatric obesity.

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Summary Background Inconsistent sleep patterns may promote excess weight gain by increasing food cravings and loss‐of‐control (LOC)‐eating; however, these relationships have not been elucidated in youth. Objective We tested whether sleep duration and timing were associated with food cravings and LOC‐eating. Method For 14 days, youths wore actigraphy monitors to assess sleep and reported severity of food cravings and LOC‐eating using ecological momentary assessment. Generalized linear mixed models tested the associations between weekly and nightly shifts in facets of sleep (i.e., duration, onset, midpoint, and waketime) and next‐day food cravings and LOC‐eating. Models were re‐run adjusting for relevant covariates (e.g., age, sex, adiposity). Results Among 48 youths (12.88 ± 2.69 years, 68.8% female, 33.3% with overweight/obesity), neither weekly nor nightly facets of sleep were significantly associated with food cravings (ps = 0.08–0.93). Youths with shorter weekly sleep duration (est. ß = −0.31, p = 0.004), earlier weekly midpoints (est. ß = −0.47, p = 0.010) and later weekly waketimes (est. ß = 0.49, p = 0.010) reported greater LOC‐eating severity; findings persisted in adjusted models. Conclusions In youth, weekly, but not nightly, shifts in multiple facets of sleep were associated with LOC‐eating severity; associations were not significant for food cravings. Sleep should be assessed as a potentially modifiable target in paediatric LOC‐eating and obesity prevention programs.

Objective: Among youth with overweight, food cravings (FC) are associated with lossof-control (LOC)-eating, but the impact of sex-associated biological characteristics on this relationship is unknown. We examined whether sex and gonadal hormone concentrations moderated the relationships between FC and LOC-eating severity among healthy boys and girls across the weight strata in natural and laboratory environments.Method: Using ecological momentary assessment (EMA), FC, and LOC-eating severity were reported 3-5 times a day for 2 weeks. In the laboratory, participants reported FC, consumed lunch from a buffet test meal designed to simulate LOC-eating, and rated LOC-eating severity during the meal.Results: Eighty-seven youth (13.0 ± 2.7 years, 58.6% female, 32.2% with overweight/obesity) participated. EMA measured general and momentary FC were positively associated with LOC-eating severity (ps < .01), with no differences by sex (ps = .21-.93). Estradiol and progesterone significantly moderated the relationships between FC and LOC-eating such that general FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) estradiol (p = .01), and momentary FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) progesterone (p = .01). Boys' testosterone did not significantly moderate the associations between FC and LOC-eating severity (ps = .36-.97). At the test meal, pre-meal FC were positively related to LOC-eating severity (p < .01), without sex or hormonal moderation (ps = .20-.64).Discussion: FC were related to LOC-eating severity in boys and girls. In the natural environment, gonadal hormones moderated this relationship in girls, but not boys.The mechanisms through which gonadal hormones might affect the relationship between FC and LOC-eating warrant investigation.

Background/objectives: Previous research indicates that youth with obesity exhibit deficits in executive functioning (EF), which often take the form of impaired response inhibition. One aspect of EF not previously studied in obesity is the adaptive process known as retrieval-induced forgetting (RIF), the suppression/inhibition of intrusive or non-target items by the retrieval of specific items from memory. The present study investigated if child or adolescent obesity disrupts the ability to inhibit retrieval of intrusive memories. Subjects/methods: We compared the manifestation of RIF in children (ages 8–12) and adolescents (ages 13–18) as a function of their weight status and sex. We also evaluated the effects of these variables on simple recall of items from episodic memory under conditions where competition from intrusive items was reduced. Results: Children with obesity did not demonstrate significant RIF, whereas RIF was exhibited by preteens without obesity and by teenage participants with- and without obesity (x Weight Status x Age Group interaction p = 0.028). This pattern of results did not differ as a function of sex for either age group. No differences in episodic memory were found. Additional analyses using Age as continuous covariate (and not as a nominal group) comparing participants who exhibited RIF with those who did not, found that the no RIF group consumed fast-food meals more frequently (p=.024) and had higher percentages of total body adiposity and android fat compared to the RIF group (p’s<.05). Conclusions: The findings expand what is known about the effects of childhood obesity on cognitive functioning, identify impaired RIF with specific behavioral and dietary factors and increased adiposity, and suggest the possibility that impairments in the ability to inhibit intrusive memories of food and eating may contribute to poor early-life weight control.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy often caused by deficiency of von Willebrand (vW) factor cleaving protease, ADAMTS-13, leading to large vW multimers and intravascular platelet aggregation. Hemolysis in TTP is mechanical and nonimmune mediated, thus Coombs testing is usually negative. We report a case of an adolescent with thrombocytopenia and Coombs positive anemia, diagnosed with Evans syndrome, but ultimately found to have TTP. TTP should be considered in children with thrombocytopenia and Coombs positive anemia who are refractory to steroids or develop signs of microangiopathy.  Recognition of this presentation can lead to life-saving treatment with plasma exchange.