Obesity‐Related Hormones in Low‐Income Preschool‐Age Children: Implications for School Readiness

Mechanisms underlying socioeconomic disparities in school readiness and health outcomes, particularly obesity, among preschool‐aged children are complex and poorly understood. Obesity can induce changes in proteins in the circulation that contribute to the negative impact of obesity on health; such changes may relate to cognitive and emotion regulation skills important for school readiness. We investigated obesity‐related hormones, body mass index ( BMI ), and school readiness in a pilot study of low‐income preschoolers attending Head Start (participating in a larger parent study). We found that the adipokine leptin was related to preschoolers' BMI z ‐score, the appetite‐regulating hormones ghrelin and glucagon‐like peptide 1 ( GLP ‐1), and pro‐inflammatory cytokines typically associated with early life stress; and that some of these obesity‐related biomarkers were in turn related to emotion regulation. Future work should evaluate how obesity may affect multiple domains of development, and consider modeling common physiological pathways related to stress, health, and school readiness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101799/1/mbe12034.pd

Associations between maternal depressive symptoms and child feeding practices in a cross-sectional study of low-income mothers and their young children

Background: Maternal depression may influence feeding practices important in determining child eating behaviors and weight. However, the association between maternal depressive symptoms and feeding practices has been inconsistent, and most prior studies used self-report questionnaires alone to characterize feeding. The purpose of this study was to identify feeding practices associated with maternal depressive symptoms using multiple methodologies, and to test the hypothesis that maternal depressive symptoms are associated with less responsive feeding practices. Methods: In this cross-sectional, observational study, participants (n = 295) included low-income mothers and their 4- to 8-year-old children. Maternal feeding practices were assessed via interviewer-administered questionnaires, semi-structured narrative interviews, and videotaped observations in home and laboratory settings. Maternal depressive symptoms were measured using the Center for Epidemiologic Studies-Depression scale (CES-D). Regression analyses examined associations between elevated depressive symptoms (CES-D score ≥16) and measures of maternal feeding practices, adjusting for: child sex, food fussiness, number of older siblings; and maternal age, body mass index (BMI), education, race/ethnicity, single parent status, perceived child weight, and concern about child weight. Results: Thirty-one percent of mothers reported depressive symptoms above the screening cutoff. Mothers with elevated depressive symptoms reported more pressuring of children to eat (β = 0.29; 95% Confidence Interval (CI): 0.03, 0.54) and more overall demandingness (β = 0.16; 95% CI: 0.03, 0.29), and expressed lower authority in child feeding during semi-structured narrative interview (Odds Ratio (OR) for low authority: 2.82; 95% CI: 1.55, 5.12). In homes of mothers with elevated depressive symptoms, the television was more likely audible during meals (OR: 1.91; 95% CI: 1.05, 3.48) and mothers were less likely to eat with children (OR: 0.48; 95% CI: 0.27, 0.85). There were no associations between maternal depressive symptoms and encouragement or discouragement of food in laboratory eating interactions. Conclusions: Mothers with elevated depressive symptoms demonstrated less responsive feeding practices than mothers with lower levels of depressive symptoms. These results suggest that screening for maternal depressive symptoms may be useful when counseling on healthy child feeding practices. Given inconsistencies across methodologies, future research should include multiple methods of characterizing feeding practices and direct comparisons of different methodologies

Acute sleep restriction increases dietary intake in preschool‐age children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136000/1/jsr12450_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136000/2/jsr12450.pd

Distinct Roles of Endothelial and Adipocyte Caveolin-1 in Macrophage Infiltration and Adipose Tissue Metabolic Activity

OBJECTIVE: Defective caveolin-1 expression is now recognized as a cause of lipoatrophic diabetes in patients, due to primary caveolin gene mutations or secondary caveolin deficiency caused by PTRF/cavin gene defects. The goal of this study was to establish the relative contribution of endothelial cells and adipocytes, both highly expressing caveolin-1 to the lipoatrophic phenotype of mice with global caveolin-1 gene invalidation (Cav1-KO). RESEARCH DESIGN AND METHODS: We compared adipose tissue development and metabolic phenotype of wild-type (WT), lipoatrophic Cav1-KO, and a murine model with specific rescue of caveolin-1 expression in endothelial cells (caveolin-1-reconstituted [Cav1-RC]). RESULTS: Defective adipose tissue development, reduced adipocyte size, and global alteration in adipose tissue gene expression that characterize lipoatrophic caveolin-1 null mice were still observed in Cav1-RC, indicating a prominent role of adipocyte-derived caveolin in lipoatrophy. We also observed that Cav1-KO adipose tissue contained an increased proportion of infiltrated macrophages compared with control mice, mostly with an alternate activation M2 phenotype. In contrast with defective lipid storage and lipoatrophy, macrophage infiltration was normalized in Cav1-RC mice, pointing to caveolin-1-dependent endothelium permeability as the causing factor for adipose tissue macrophage infiltration in this model. CONCLUSIONS: This is the first report of a specific role for adipocyte caveolin expression in lipid storage. Our study also shows that endothelium caveolin critically participates in the control of macrophage extravasation from the blood into adipose tissue, therefore establishing distinct roles depending on topology of caveolin expression in different cell types of adipose tissue

Family conflict, chaos, and negative life events predict cortisol activity in low‐income children

Childhood poverty is hypothesized to increase risk for mental and physical health problems at least in part through dysregulation of the hypothalamic‐pituitary‐adrenal axis. However, less is known about the specific psychosocial stressors associated with cortisol reactivity and regulation for children living in poverty. The current study investigates negative life events, household chaos, and family conflict in preschool and middle childhood as potential predictors of cortisol regulation in low‐income 7–10 year olds (N = 242; M age = 7.9 years). Participants were assessed in preschool and participated in a follow‐up assessment in middle childhood, during which diurnal free cortisol and free cortisol reactivity to the Trier Social Stress Test for Children (TSST‐C) were assessed. Household chaos during preschool predicted a more blunted diurnal cortisol slope in middle childhood. Greater negative life events during preschool and greater concurrent family conflict were associated with increased free cortisol reactivity in middle childhood.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144279/1/dev21602_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144279/2/dev21602.pd

The IKKâ related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists

The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogeneâ induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through siteâ specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGFâ receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i.e., TLR3; TLR4), revealing a stimulusâ selective role for TBK1 in mTORC1 regulation. By studying cultured macrophages and those isolated from genome edited mTOR S2159A knockâ in mice, we show that mTOR S2159 phosphorylation promotes mTORC1 signaling, IRF3 nuclear translocation, and IFNâ β production. These data demonstrate a direct mechanistic link between TBK1 and mTORC1 function as well as physiologic significance of the TBK1â mTORC1 axis in control of innate immune function. These data unveil TBK1 as a direct mTORC1 activator and suggest unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity, tumorigenesis, and disorders linked to chronic inflammation.SynopsisTBK1, an IKKâ related kinase that drives interferon production as well cancer cell proliferation and survival, phosphorylates mTOR to activate mTORC1 in response to EGF and innate immune agonists, suggesting unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity and tumorigenesis.TBK1 interacts with mTORC1 and phosphorylates mTOR on S2159 to increase its catalytic activity.Cells lacking TBK1 or expressing a mTOR S2159A allele exhibit reduced mTORC1 signaling in response to EGFâ receptor and TLR3/4 activation.Primary macrophages derived from genome edited mTOR S2159A mice exhibit reduced mTORC1 signaling in response to TLR3/4 activation.Primary macrophages treated with rapamycin as well as those derived from mTORS2159A mice produce reduced levels of IFNâ β due to impaired nuclear translocation of the transcription factor IRF3.Innate immune kinase TBK1â dependent activation of mTORC1 occurs in response to pathogen recognition and EGF receptor activation and drives interferon production, thus highlighting the role of mTOR for innate immunity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/1/embj201696164.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/2/embj201696164.reviewer_comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/3/embj201696164_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/4/embj201696164-sup-0001-EVFigs.pd