Biochemical Phenomena, Metabolism, and Nutrition Commons^™

The Central Melanocortin System And Human Obesity, Yongjie Yang, Yong Xu

Children’s Nutrition Research Center Staff Publications

The prevalence of obesity and the associated comorbidities highlight the importance of understanding the regulation of energy homeostasis. The central melanocortin system plays a critical role in controlling body weight balance. Melanocortin neurons sense and integrate the neuronal and hormonal signals, and then send regulatory projections, releasing anorexigenic or orexigenic melanocortin neuropeptides, to downstream neurons to regulate the food intake and energy expenditure. This review summarizes the latest progress in our understanding of the role of the melanocortin pathway in energy homeostasis. We also review the advances in the identification of human genetic variants that cause obesity via mechanisms that …

The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes.

Objective: This paper presents the rationale, implementation, …

Paraventricular Hypothalamus Mediates Diurnal Rhythm Of Metabolism, Eun Ran Kim, Yuanzhong Xu, Ryan M Cassidy, Yungang Lu, Yongjie Yang, Jinbin Tian, De-Pei Li, Rachel Van Drunen, Aleix Ribas-Latre, Zhao-Lin Cai, Mingshan Xue, Benjamin R Arenkiel, Kristin Eckel-Mahan, Yong Xu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening …

Disrupted Hypothalamic Crh Neuron Responsiveness Contributes To Diet-Induced Obesity, Canjun Zhu, Yuanzhong Xu, Zhiying Jiang, Jin Bin Tian, Ryan M Cassidy, Zhao-Lin Cai, Gang Shu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qingyan Jiang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both …

Alteration Of The Gut Microbiome In Normal And Overweight School Children From Selangor With Lactobacillus Fermented Milk Administration, Narcisse Joseph, Jonathan B. Clayton, Susan L. Hoops, Carter A. Linhardt, Amalia Mohd Hashim, Barakatun Nisak Mohd Yusof, Suresh Kumar, Syafinaz Amin Nordin

Food for Health: Publications

Childhood obesity is a serious public health problem worldwide. Perturbations in the gut microbiota composition have been associated with the development of obesity in both children and adults. Probiotics, on the other hand, are proven to restore the composition of the gut microbiome which helps reduce the development of obesity. However, data on the effect of probiotics on gut microbiota and its association with childhood obesity is limited. This study aims to determine the effect of probiotics supplement intervention on gut microbiota profiles in obese and normal-weight children. A total of 37 children, 17 normal weight, and 20 overweight school …

Constraint And Trade-Offs Regulate Energy Expenditure During Childhood, Samuel S. Urlacher, J. Josh Snodgrass, Lara R. Dugas, Lawrence S. Sugiyama, Melissa A. Liebert

Biostatistics Collaborative Core: Faculty Publications and Other Works

Children’s metabolic energy expenditure is central to evolutionary and epidemiological frameworks for understanding variation in human phenotype and health. Nonetheless, the impact of a physically active lifestyle and heavy burden of infectious disease on child metabolism remains unclear. Using energetic, activity, and biomarker measures, we show that Shuar forager-horticulturalist children of Amazonian Ecuador are ~25% more physically active and, in association with immune activity, have ~20% greater resting energy expenditure than children from industrial populations. Despite these differences, Shuar children’s total daily energy expenditure, measured using doubly labeled water, is indistinguishable from industrialized counterparts. Trade-offs in energy allocation between competing …

Steroid Receptor Coactivator-1 Modulates The Function Of Pomc Neurons And Energy Homeostasis, Yongjie Yang, Agatha A Van Der Klaauw, Liangru Zhu, Tessa M Cacciottolo, Yanlin He, Lukas K J Stadler, Chunmei Wang, Pingwen Xu, Kenji Saito, Antentor Hinton, Xiaofeng Yan, Julia M Keogh, Elana Henning, Matthew C Banton, Audrey E Hendricks, Elena G Bochukova, Vanisha Mistry, Katherine L Lawler, Lan Liao, Jianming Xu, Stephen O'Rahilly, Qingchun Tong, Uk10k Consortium, Inês Barroso, Bert W O'Malley, I Sadaf Farooqi, Yong Xu

Children’s Nutrition Research Center Staff Publications

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function …

An Interface Of The Taste And Reward Systems In The Brainstem And Its Role In Feeding, Louis Saites

Theses and Dissertations (ETD)

We eat what tastes good. We also eat because it is necessary for our health. In fact, some of the most nutritious foods (e.g., vegetables) are often less appetizing, and the tastiest (e.g., fast food, ice cream) may be the least healthy. Despite the former, we may also have a lower limit of what we accept at which point nutrition becomes irrelevant (e.g., “spinach is just too yucky”). Further, we may eat unhealthily because of overwhelming urges. We investigated the complex interactions of taste and feeding at the neurobiological level using the experiments described.

In one sense, this neurobiology begins …

Very Low-Carbohydrate, High-Fat, Weight Reduction Diet Decreases Hepatic Gene Response To Glucose In Obese Rats, Kathleen V. Axen, Marianna A. Harper, Yu Fu Kuo, Kenneth Axen

Publications and Research

Background: Very low carbohydrate (VLC) diets are used to promote weight loss and improve insulin resistance (IR) in obesity. Since the high fat content of VLC diets may predispose to hepatic steatosis and hepatic insulin resistance, we investigated the effect of a VLC weight-reduction diet on measures of hepatic and whole body insulin resistance in obese rats.

Methods: In Phase 1, adult male Sprague-Dawley rats were made obese by ad libitum consumption of a high-fat (HF1, 60% of energy) diet; control rats ate a lower-fat (LF, 15%) diet for 10 weeks. In Phase 2, obese rats were fed energy-restricted amounts …

Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E. Smith, Laurence D. Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A. Hidalgo, Stella Aslibekyan, Michael A. Province, Devin Absher, Donna K. Arnett, Katherine L. Tucker, Jose M. Ordovas

Epidemiology and Environmental Health Faculty Publications

Background: The putative functional variant −265T > C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.

Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.

Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (< 22 g/d) or high-SFA diet (≥ 22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

Role Of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-Sdkp) And Renal Hemodynamics On Obesity Related Renal Damage, Mani Maheshwari

Theses, Dissertations and Capstones

Obesity is a public health problem and is associated with salt-sensitive hypertension, kidney inflammation and fibrosis. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a tetra-peptide with anti-inflammatory and anti-fibrotic properties but its effect on kidney damage in obesity is unknown. We hypothesized that high salt fed Zucker obese (ZO) rats develop renal damage, inflammation and fibrosis and that Ac-SDKP prevents these changes. Zucker lean (ZL) rats served as controls. Animals were treated with Ac-SDKP while maintained on either a normal-salt or HS diet for 8 weeks. Systolic blood pressure (SBP), albuminuria, renal inflammation and fibrosis were evaluated. HS diet increased macrophage infiltration in the …

Obesity, Metabolic Factors And Risk Of Different Histological Types Of Lung Cancer: A Mendelian Randomization Study, Robert Carreras-Torres, Mattias Johansson, Philip C. Haycock, Kaitlin H. Wade, Caroline L. Relton, Richard M. Martin, George Davey Smith, Demetrius Albanes, Melinda C. Aldrich, Angeline Andrew, Susanne M. Arnold, Heike Bickeböller, Stig E. Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E. Caporaso, Chu Chen, David C. Christiani, Warren Jay Christian, Jennifer A. Doherty, Eric J. Duell, John K. Field, Michael P. A. Davies, Michael W. Marcus, Gary E. Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A. Kiemeney

Markey Cancer Center Faculty Publications

Background

Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.

Methods and findings

We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of …

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, Phd, Joseph I. Shapiro, Md

Marshall Journal of Medicine

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification for ROS with circulating …

Stability Of Metabolic Factor Before And After Bariatric Surgery, Brandon Davis, Joseph Indelicato

The School of Health Sciences Publications and Research

No abstract provided.

Platelet-Activating Factor Receptor Affects Food Intake And Body Weight, Wei Li, Thomas M. Mcintyre

Biomedical Sciences

“Let’s Move!” is a comprehensive initiative, launched by the First Lady, Michelle Obama, dedicates to solving problems of obesity, which is growing in child. The life behaviors do affect obesity; however, the mechanistic insight in molecular level is still not clear. In this study, by continually monitoring mouse body weight under chow and high fat western diets as well as metabolic, physical activity and food intake behaviors assessed in a CLAMS Comprehensive Lab Animal Monitoring System, we demonstrated that the platelet-activating factor receptor (PTAFR) contributes to modification of life behaviors. PTAFR does not affect metabolism of ingested dietary fat and …

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated By Ho-1-Sirt1 Module In Murine Hepatocytes And Mice Fed A High Fructose Diet, Komal Sodhi, Nitin Puri, Gaia Favero, Sarah Stevens, Charles Meadows, Nader G. Abraham, Rita Rezzani, Hayden A. Ansinelli, Edward Lebovics, Joseph I. Shapiro

Biochemistry and Microbiology

Background

Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.

Hypothesis

We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.

Methods …

Characterization Of Ghrelin O-Acyltransferase Active Site, Leslie Patton

Renée Crown University Honors Thesis Projects - All

Ghrelin, first discovered in 1999, is a 28-amino acid peptide hormone involved in the regulation of appetite, insulin secretion and sensitivity, and many neurological effects such as learning, memory, and depression.^1-6 Ghrelin has been identified to have a unique posttranslational octanoylation carried out by the enzyme ghrelin O-acyltransferase (GOAT). This distinctive modification is a point of interest in studying GOAT whereby blocking the acylation of the ghrelin could potentially halt the activity of the peptide hormone and provide a means of treating obesity, diabetes, and other diseases affected by ghrelin levels. The duration of my project involved working …

Body Mass Index Or Body Fat! Which Is A Better Obesity Scale For Pakistani Population?, Syeda Sadia Fatima, Rehana Rehman, Bushra Chaudhry

Department of Biological & Biomedical Sciences

Ojective: To compare two methods of classifying obesity based on body mass index and body fat percentage.
Methods: The cross-sectional study was conducted from November 2012 to August 2013 at Jinnah Postgraduate Medical Centre, Karachi. Male and female volunteers between the ages 15-65 years were selected using simple random sampling. They were classified into different groups for body mass index and body fat percentage measured through bioelectrical impedance scale. The subjects were sub-grouped into underweight, normal weight, overweight and obese. SPSS 11 was used for statistical analysis.
Results: The mean age of the 828 healthy volunteers was 25.67±10.10 years. A …

An Investigation Of Perinatal Polychlorinated Biphenyl Exposure On Body Composition And Glucose Homeostasis, Cetewayo S. Rashid

Theses and Dissertations--Nutritional Sciences

Recent advancements have uncovered environmental contributions to obesity and diabetes etiology. In fact, perinatal malnutrition resulting in low birth weight (LBW) has been shown to correlate with later life obesity and impaired glucose tolerance in aged offspring. LBW can result from a myriad of developmental perturbations including macronutrient restriction, hypoxia, maternal stress and toxin exposure.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that bioaccumulate in the food chain resulting in dietary exposure in humans. Maternal and cord blood PCB levels are inversely associated with birth weight, and recent studies indicate that perinatal exposures to PCBs contribute to gender-specific obesity development …

Effects Of Adipocyte Deficiency Of Angiotensin Type 1a Receptors In Models Of Obesity And Hypercholesterolemia, Kelly Anne Putnam

Theses and Dissertations--Nutritional Sciences

Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a …