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

CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/1/jlb1107-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/2/jlb1107-sup-0003.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/3/jlb1107.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/4/jlb1107-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/5/jlb1107-sup-0004.pd

Weight Regain in Formerly Obese Mice Hastens Development of Hepatic Steatosis Due to Impaired Adipose Tissue Function

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/1/oby22788-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/2/oby22788_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/3/oby22788.pd

CX 3 CR1 Deficiency Does Not Influence Trafficking of Adipose Tissue Macrophages in Mice With Diet‐Induced Obesity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93703/1/oby.2012.7.pd

Neuropeptide Y Is Produced by Adipose Tissue Macrophages and Regulates Obesity-Induced Inflammation

<div><p>Neuropeptide Y (NPY) is induced in peripheral tissues such as adipose tissue with obesity. The mechanism and function of NPY induction in fat are unclear. Given the evidence that NPY can modulate inflammation, we examined the hypothesis that NPY regulates the function of adipose tissue macrophages (ATMs) in response to dietary obesity in mice. NPY was induced by dietary obesity in the stromal vascular cells of visceral fat depots from mice. Surprisingly, the induction of <i>Npy</i> was limited to purified ATMs from obese mice. Significant basal production of NPY was observed in cultured bone marrow derived macrophage and dendritic cells (DCs) and was increased with LPS stimulation. <i>In vitro</i>, addition of NPY to myeloid cells had minimal effects on their activation profiles. NPY receptor inhibition promoted DC maturation and the production of IL-6 and TNFα suggesting an anti-inflammatory function for NPY signaling in DCs. Consistent with this, NPY injection into lean mice decreased the quantity of M1-like CD11c⁺ ATMs and suppressed Ly6c^hi monocytes. BM chimeras generated from <i>Npy^−/−</i> donors demonstrated that hematopoietic NPY contributes to the obesity-induced induction of <i>Npy</i> in fat. In addition, loss of <i>Npy</i> expression from hematopoietic cells led to an increase in CD11c⁺ ATMs in visceral fat with high fat diet feeding. Overall, our studies suggest that NPY is produced by a range of myeloid cells and that obesity activates the production of NPY in adipose tissue macrophages with autocrine and paracrine effects.</p> </div

The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health

Objective: Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their significance in adipose tissue metabolism and physiology has not been demonstrated in vivo. We previously identified Blnc1 as a conserved lncRNA regulator of brown and beige adipocyte differentiation. In this study, we investigated the physiological role of Blnc1 in thermogenesis, adipose remodeling and systemic metabolism. Methods: We generated fat-specific Blnc1 transgenic and conditional knockout mouse strains and investigated how adipocyte Blnc1 levels are causally linked to key aspects of metabolic health following diet-induced obesity. We performed studies using cultured adipocytes to establish cell-autonomous role of Blnc1 in regulating adipocyte gene programs. Results: Blnc1 is highly induced in both brown and white fats from obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning and exacerbates obesity-associated brown fat whitening, adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation and homeostatic remodeling during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. Conclusions: This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health. Keywords: lncRNA, Adipose tissue remodeling, Brown fat, White fat, Whitening, Inflammation, Obesit

An MHC II-Dependent Activation Loop between Adipose Tissue Macrophages and CD4+ T Cells Controls Obesity-Induced Inflammation

An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4+ T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs) and CD4+ T cells contribute to adipose tissue metainflammation. Intravital microscopy identifies dynamic antigen-dependent interactions between ATMs and T cells in visceral fat. Mice deficient in major histocompatibility complex class II (MHC II) showed protection from diet-induced obesity. Deletion of MHC II expression in macrophages led to an adipose tissue-specific decrease in the effector/memory CD4+ T cells, attenuation of CD11c+ ATM accumulation, and improvement in glucose intolerance by increasing adipose tissue insulin sensitivity. Ablation experiments demonstrated that the maintenance of proliferating conventional T cells is dependent on signals from CD11c+ ATMs in obese mice. These studies demonstrate the importance of MHCII-restricted signals from ATMs that regulate adipose tissue T cell maturation and metainflammation

Lack of NPY expression in hematopoietic cells increases M1 ATMs with diet-induced obesity.

<p>Donor marrow from S129 wildtype and S129 <i>Npy^−/−</i> mice were transplanted into lethally irradiated wild-type S129 mice. After reconstitution, both groups were placed on ND or HFD chow for 8 weeks (N = 5 in WT donor groups, N = 4 in KO donor groups). (A) Body Weight and (B) EWAT weight assessed at the end of the diet exposure. (C) Flow cytometry quantitation of ATMs (F4/80, CD11b) expressed as number for total per EWAT fat pad (D) ATM as percent of leukocytes in EWAT by flow cytometry. (E) Flow cytometry quantitation of F4/80⁺ CD11b⁺CD11c⁺ ATMs (M1) and F4/80⁺ CD11b⁺CD11c⁺ MHCII⁺ ATMs. (F) <i>Npy</i> expression in EWAT of BM chimeras by RT-PCR. (G) <i>Tnfa</i> EWAT gene expression by RT-PCR. (H) Fasting insulin levels from serum after 6 hour fast. *p<0.05, groups compared by two-way ANOVA and signficance values shown by individual t-tests.</p