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M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling

August 15, 2015

Abstract Endothelial nitric oxide (NO) signaling plays a physiological role in limiting obesity-associated insulin resistance and inflammation. This study was undertaken to investigate whether this NO effect involves polarization of macrophages toward an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase overexpression were protected against high-fat diet (HFD)-induced hepatic inflammation and insulin resistance, and this effect was associated with reduced proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer cells. In cell culture studies, exposure of macrophages to endothelial NO similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene expression. Similar effects were induced by macrophage overexpression of vasodilator-stimulated … Read More »

Categories: Publications Tags: University of Washington

Long-Chain Polyunsaturated Fatty Acids Attenuate the IL-1β-Induced Proinflammatory Response in Human Fetal Intestinal Epithelial Cells

August 13, 2015

Abstract Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. Citation Wijendran V, Brenna JT, Wang DH, Zhu W, Meng D, Ganguli K, Kothapalli KS, Requena P, Innis S, Walker WA. Long-chain polyunsaturated fatty acids attenuate the IL-1β-induced proinflammatory response in human fetal intestinal epithelial cells. Pediatr Res. 2015 Dec;78(6):626-33. PMID: 26270575; PMCID: PMC5046822. Read MorePediatric Research Research Details Research Center: Harvard Medical School … Read More »

Categories: Publications Tags: Harvard Medical School

Hematopoietic Androgen Receptor Deficiency Promotes Visceral Fat Deposition in Male Mice Without Impairing Glucose Homeostasis

July 15, 2015

Abstract Androgen deficiency in men increases body fat, but the mechanisms by which testosterone suppresses fat deposition have not been elucidated fully. Adipose tissue macrophages express the androgen receptor (AR) and regulate adipose tissue remodeling. Thus, testosterone signaling in macrophages could alter the paracrine function of these cells and thereby contribute to the metabolic effects of androgens in men. A metabolic phenotyping study was performed to determine whether the loss of AR signaling in hematopoietic cells results in greater fat accumulation in male mice. C57BL/6J male mice (ages 12-14 weeks) underwent bone marrow transplant from either wild-type (WT) or AR … Read More »

Categories: Publications Tags: University of Washington

Obesity-Associated Biomarkers and Executive Function in Children

July 1, 2015

Abstract There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer’s disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, obesity-associated inflammatory cytokines, and obesity-associated gut hormones have been associated with learning, memory, and general cognitive function. To date, examination of obesity-associated biology with brain function has primarily occurred in animal models. The few … Read More »

Categories: Publications Tags: University of Michigan

Plasma Vitamin D is Associated with Fasting Insulin and Homeostatic Model Assessment of Insulin Resistance in Young Adult Males, But Not Females, of the Jerusalem Perinatal Study

May 30, 2015

Abstract The goal of this study was to examine cross-sectional relationships between plasma vitamin D and cardiometabolic risk factors in young adults. Data were collected from interviews, physical examinations and biomarker measurements. Total plasma 25-hydroxyvitamin D (25(OH)D) was measured using LC-tandem MS. Associations between 25(OH)D and cardiometabolic risk factors were modelled using weighted linear regression with robust estimates of standard errors. Participants of the Jerusalem Perinatal Study (n 1204) interviewed and examined at age 32 years. Participants were oversampled for low and high birth weight and for maternal pre-pregnancy obesity. We found evidence for inverse associations of 25(OH)D with markers … Read More »

Categories: Publications Tags: University of Washington

Whole Exome Sequencing Identifies RAI1 Mutation in a Morbidly Obese Child Diagnosed with ROHHAD Syndrome

May 17, 2015

Abstract The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis. To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. This publication highlights the potential overlap between ROHHAD syndrome and Smith-Magenis syndrome (SMS) and … Read More »

Categories: Publications Tags: Harvard Medical School

Vitamin D Metabolites and Bone Mineral Density: The Multi-Ethnic Study of Atherosclerosis

May 11, 2015

Abstract Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D) concentrations with low bone mineral density (BMD) and fractures, motivating widespread use of vitamin D supplements for bone health. However, previous studies have been limited to predominantly White populations despite differences in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH2)D3), and parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi-Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study design. Vitamin D metabolites were measured using liquid chromatography-mass spectroscopy and PTH using a 2-site immunoassay from serum collected … Read More »

Categories: Publications Tags: University of Washington

In Vivo Structure-Function Studies of Human Hepatic Lipase

April 30, 2015

Abstract The lean body weight phenotype of hepatic lipase (HL)-deficient mice (hl(-/-)) suggests that HL is required for normal weight gain, but the underlying mechanisms are unknown. HL plays a unique role in lipoprotein metabolism performing bridging as well as catalytic functions, either of which could participate in energy homeostasis. To determine if both the catalytic and bridging functions or the catalytic function alone are required for the effect of HL on body weight, we studied (hl(-/-)) mice that transgenically express physiologic levels of human (h)HL (with catalytic and bridging functions) or a catalytically-inactive (ci)HL variant (with bridging function only) … Read More »

Categories: Publications Tags: University of Washington

Islet 1 Specifies the Identity of Hypothalamic Melanocortin Neurons and is Critical for Normal Food Intake and Adiposity in Adulthood

April 14, 2015

Abstract Food intake and body weight regulation depend on a group of hypothalamic neurons that release satiety-induced neuropeptides known as melanocortins. Central melanocortins are encoded by the proopiomelanocortin gene (Pomc), and mice and humans carrying deleterious mutations in the Pomc gene display hyperphagia and severe obesity. Although the importance of these neurons is well understood, the genetic program that establishes hypothalamic melanocortin neurons and maintains normal Pomc expression levels remains unknown. Here, we combined molecular neuroanatomical and biochemical analyses with functional genetic studies in transgenic mice and zebrafish and discovered that the transcription factor Islet 1 determines the identity of … Read More »

Categories: Publications Tags: University of Michigan

Effects of Murine Norovirus on Atherosclerosis in Ldlr Mice Depends on Timing of Infection

April 1, 2015

Abstract We previously reported that murine norovirus (MNV), a virus prevalent in United States research institutions, increased atherosclerotic lesion size in Ldlr(-/-) mice when the mice were infected 8 wk after feeding an atherogenic diet. To determine whether the timing of MNV infection relative to atherosclerosis development altered the disease phenotype and to examine potential mechanisms by which MNV influences the disease process, we fed Ldlr(-/-) mice an atherogenic diet for 16 wk. Three days after initiating the atherogenic diet, half of the mice received MNV4 and the other half vehicle only (clarified cell-culture lysate; controls). Both groups of mice … Read More »

Categories: Publications Tags: University of Washington