Hypothalamic Gliosis is Associated With Multiple Cardiovascular Disease Risk Factors.

Background: Hypothalamic gliosis is mechanistically linked to obesity and insulin resistance in rodent models. We tested cross-sectional associations between radiologic measures of hypothalamic gliosis in humans and clinically relevant cardiovascular disease risk factors, as well as prevalent coronary heart disease.

Methods: Using brain MRI images from Framingham Heart Study participants (N=867; mean age, 55 years; 55% females), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala (AMY) and putamen (PUT).

Associations of radiologic characteristics of the neonatal hypothalamus with early life adiposity gain.

Background: The mediobasal hypothalamus (MBH) is a key brain area for regulation of energy balance. Previous neuroimaging studies suggest that T2-based signal properties indicative of cellular inflammatory response (gliosis) are present in adults and children with obesity, and predicts greater adiposity gain in children at risk of obesity.

Objectives/methods: The current study aimed to extend this concept to the early life period by considering if, in full-term healthy neonates (up to n = 35), MRI evidence of MBH gliosis is associated with changes in early life (neonatal to six months) body fat percentage measured by DXA.

In utero exposure to maternal diabetes or hypertension and childhood hypothalamic gliosis.

Exposure to maternal diabetes (DM) or hypertension (HTN) during pregnancy impacts offspring metabolic health in childhood and beyond. Animal models suggest that induction of hypothalamic inflammation and gliosis in the offspring's hypothalamus is a possible mechanism mediating this effect. We tested, in children, whether in utero exposures to maternal DM or HTN were associated with mediobasal hypothalamic (MBH) gliosis as assessed by brain magnetic resonance imaging (MRI).

Central androgen action reverses hypothalamic astrogliosis and atherogenic risk factors induced by orchiectomy and high-fat diet feeding in male mice.

Hypogonadism in males confers elevated cardiovascular disease (CVD) risk by unknown mechanisms. Recent radiological evidence suggests that low testosterone (T) is associated with mediobasal hypothalamic (MBH) gliosis, a central nervous system (CNS) cellular response linked to metabolic dysfunction. To address mechanisms linking CNS androgen action to CVD risk, we generated a hypogonadal, hyperlipidemic mouse model with orchiectomy (ORX) combined with hepatic PCSK9 overexpression.

The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans.

Accumulated preclinical literature demonstrates that hypothalamic inflammation and gliosis are underlying causal components of diet-induced obesity in rodent models. This review summarizes and synthesizes available translational data to better understand the applicability of preclinical findings to human obesity and its comorbidities. The published literature in humans includes histopathologic analyses performed postmortem and in vivo neuroimaging studies measuring indirect markers of hypothalamic tissue microstructure.

Exposure to Gestational Diabetes Mellitus Prior to 26 Weeks Is Related to the Presence of Mediobasal Hypothalamic Gliosis in Children.

Intrauterine exposure to metabolic dysfunction leads to offspring metabolic dysfunction in human and rodent models, but underlying mechanisms are unclear. The mediobasal hypothalamus (MBH) is involved in energy homeostasis and weight regulation, and MBH gliosis is associated with obesity and insulin resistance. We tested the hypothesis that offspring exposed to gestational diabetes mellitus (GDM) in utero versus those unexposed would show evidence of MBH gliosis.

Impaired Brain Satiety Responses After Weight Loss in Children With Obesity.

Context: Obesity interventions often result in increased motivation to eat.

Objective: We investigated relationships between obesity outcomes and changes in brain activation by visual food cues and hormone levels in response to obesity intervention by family-based behavioral treatment (FBT).

Methods: Neuroimaging and hormone assessments were conducted before and after 24-week FBT intervention in children with obesity (OB, n = 28), or children of healthy weight without intervention (HW, n = 17), all 9- to 11-year-old boys and girls.

Evidence That Hypothalamic Gliosis Is Related to Impaired Glucose Homeostasis in Adults With Obesity.

Objective: Preclinical research implicates hypothalamic glial cell responses in the pathogenesis of obesity and type 2 diabetes (T2D). In the current study we sought to translate such findings to humans by testing whether radiologic markers of gliosis in the mediobasal hypothalamus (MBH) were greater in individuals with obesity and impaired glucose homeostasis or T2D.

Research Design And Methods: Using cross-sectional and prospective cohort study designs, we applied a validated quantitative MRI approach to assess gliosis in 67 adults with obesity and normal glucose tolerance, impaired glucose tolerance (IGT), or T2D.

Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity.

Objective: This study investigated, in a large pediatric population, whether magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) gliosis is associated with baseline or change over 1 year in body adiposity.

Methods: Cross-sectional and prospective cohort analyses were conducted within the Adolescent Brain Cognitive Development Study. Study 1 included 169 children with usable baseline T2-weighted MRI images and anthropometrics from baseline and 1-year follow-up study visits.

General and Food-Specific Impulsivity and Inhibition Related to Weight Management.

Understanding child characteristics that relate to weight management treatment outcome could help identify opportunities for intervention innovation or tailoring. The limited evidence available is inconsistent regarding whether and which aspects of children's general or food-specific impulsivity and inhibition relate to treatment outcomes. Children with ( = 54) and without obesity ( = 22) were compared on various measures of impulsivity and inhibition.

Reassessing relationships between appetite and adiposity in people at risk of obesity: A twin study using fMRI.

Background: Neuroimaging studies suggest that appetitive drive is enhanced in obesity.

Objective: To test if appetitive drive varies in direct proportion to the level of body adiposity after accounting for genetic factors that contribute to both brain response and obesity risk.

Subjects/methods: Participants were adult monozygotic (n = 54) and dizygotic (n = 30) twins with at least one member of the pair with obesity.

Pilot multi-site and reproducibility study of hypothalamic gliosis in children.

Objective: Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of gliosis.

Methods: Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of gliosis) by region and to assess relationships with age and BMI.

Child neurobiology impacts success in family-based behavioral treatment for children with obesity.

Background And Objectives: Family-based behavioral treatment (FBT) is the recommended treatment for children with common obesity. However, there is a large variability in short- and long-term treatment response, and mechanisms for unsuccessful treatment outcomes are not fully understood. In this study, we tested if brain response to visual food cues among children with obesity before treatment predicted weight or behavioral outcomes during a 6-month behavioral weight management program and/or long-term relative weight maintenance over a 1-year follow-up period.

Effects of multiple cycles of weight loss and regain on the body weight regulatory system in rats.

We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. Thirty-six male Wistar rats were divided into three weight-matched groups: weight cyclers ( = 18), ad libitum-fed controls ( = 9), and maturity controls ( = 9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding.

Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

Background/objectives: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB).

Evaluating Relationships between Visceral Fat Measures and Adipokines Concentrations among Women with a History of Preeclampsia.

Objective: We sought to evaluate associations between postpartum plasma adipokine concentrations among women with a history of preeclampsia (PE) without severe features (MPE), PE with severe features (SPE), and no PE (NPE). We also investigated relationships between adipokines and computed tomography (CT)-quantified measures of visceral fat (VF) area (VFA) and subcutaneous fat area (SCFA).

Study Design: We performed a secondary analysis of data collected as part of a previously performed cross-sectional study at our institution.

Salience network connectivity is reduced by a meal and influenced by genetic background and hypothalamic gliosis.

Background/objectives: The salience network (SN) comprises brain regions that evaluate cues in the external environment in light of internal signals. We examined the SN response to meal intake and potential genetic and acquired influences on SN function.

Subjects/methods: Monozygotic (MZ; 40 pairs) and dizygotic (15 pairs) twins had body composition and plasma metabolic profile evaluated (glucose, insulin, leptin, ghrelin, and GLP-1).

Adipokine profiles in preeclampsia.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE), are associated with short- and long-term maternal health complications, and obesity is a leading attributable risk factor for HDP. Yet, most women identified as obese [by body mass index (BMI) ≥ 30 kg/m] do not develop HDP, indicating limited predictability of BMI alone. In nonpregnant populations, increased visceral fat mass (VFM) is an obesity-associated phenotype increasing the risk of developing hypertension.

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen-level dependent response to glucose ingestion.

Objective: In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity.

Methods: Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion.

Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men.

Objective: This study aimed to determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men.

Methods: A total of 41 adult men (aged 18-50 years) from 23 twin pairs underwent fasting morning blood draw and brain magnetic resonance imaging. T2 relaxation time was used to quantify gliosis in the MBH and control areas in the putamen and amygdala.

Central Nervous System and Peripheral Hormone Responses to a Meal in Children.

Context: Behavioral studies suggest that responses to food consumption are altered in children with obesity (OB).

Objective: To test central nervous system and peripheral hormone response by functional MRI and satiety-regulating hormone levels before and after a meal.

Design And Setting: Cross-sectional study comparing children with OB and children of healthy weight (HW) recruited from across the Puget Sound region of Washington.

FTO genotype impacts food intake and corticolimbic activation.

Background: Variants in the first intron of the fat mass and obesity-associated (FTO) gene increase obesity risk. People with "high-risk" FTO genotypes exhibit preference for high-fat foods, reduced satiety responsiveness, and greater food intake consistent with impaired satiety.

Objective: We sought central nervous system mechanisms that might underlie impaired satiety perception in people with a higher risk of obesity based on their FTO genotype.

Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status.

Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness.

A closer look at the subordinate population within the visible burrow system.

The visible burrow system (VBS) utilizes the natural social behavior of rodents to model chronic social stress. Classically, when male and female rats are housed together in the VBS a dominance hierarchy rapidly forms with one dominant (DOM) and three subordinate (SUB) males. SUB animals show signs of chronic social stress, including loss of body weight and elevated basal corticosterone.

Using Make for Reproducible and Parallel Neuroimaging Workflow and Quality-Assurance.

The contribution of this paper is to describe how we can program neuroimaging workflow using Make, a software development tool designed for describing how to build executables from source files. A makefile (or a file of instructions for Make) consists of a set of rules that create or update target files if they have not been modified since their dependencies were last modified. These rules are processed to create a directed acyclic dependency graph that allows multiple entry points from which to execute the workflow.