Biochemical Phenomena, Metabolism, and Nutrition Commons^™

When A Calorie Is Not Just A Calorie: Diet Quality And Timing As Mediators Of Metabolism And Healthy Aging, Maria M Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, Zheng Chen, William W Ja, Michele Shirasu-Hiza, Mary N Latimer, Julie A Mattison, Anna E Thalacker-Mercer, Vishwa Deep Dixit, Satchidananda Panda, Dudley W Lamming

Faculty, Staff and Student Publications

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that "a calorie is just a calorie," there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and …

Creativity In Energy Balance, Obesity And Feeding Behavior Research, Some Thoughts, Stephen J French, David B Allison

Children’s Nutrition Research Center Staff Publications

This review provides an overview of examples of especially creative work related to the fields of ingestive behavior, energetics (defined as the study of the acquisition, storage, and use of metabolizable energy by biological organisms and the causes and consequences of such acquisition, storage, and use), and nutrition, focusing on both individual works and discoveries, as well as bodies of works and in some cases the working styles of particular scientists. The paper then discusses some principles extracted from our observations as well as from the literature on creativity pointing out some factors that seem to make for more creative …

Birth Weight Moderates The Association Between Obesity And Mortality Rate, Gregory Pavela, Nengjun Yi, Luis Mestre, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Purpose: The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.

Methods: Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional …

Lateral Septum As A Melanocortin Downstream Site In Obesity Development, Yuanzhong Xu, Zhiying Jiang, Hongli Li, Jing Cai, Yanyan Jiang, Joshua Otiz-Guzman, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons …

The Melanocortin Action Is Biased Toward Protection From Weight Loss In Mice, Hongli Li, Yuanzhong Xu, Yanyan Jiang, Zhiying Jiang, Joshua Otiz-Guzman, Jessie C Morrill, Jing Cai, Zhengmei Mao, Yong Xu, Benjamin R Arenkiel, Cheng Huang, Qingchun Tong

Faculty, Staff and Student Publications

The melanocortin action is well perceived for its ability to regulate body weight bidirectionally with its gain of function reducing body weight and loss of function promoting obesity. However, this notion cannot explain the difficulty in identifying effective therapeutics toward treating general obesity via activation of the melanocortin action. Here, we provide evidence that altered melanocortin action is only able to cause one-directional obesity development. We demonstrate that chronic inhibition of arcuate neurons expressing proopiomelanocortin (POMC) or paraventricular hypothalamic neurons expressing melanocortin receptor 4 (MC4R) causes massive obesity. However, chronic activation of these neuronal populations failed to reduce body weight. …

Identification Of A Gabaergic Neural Circuit Governing Leptin Signaling Deficiency-Induced Obesity, Yong Han, Yang He, Lauren Harris, Yong Xu, Qi Wu

Faculty, Staff and Students Publications

The hormone leptin is known to robustly suppress food intake by acting upon the leptin receptor (LepR) signaling system residing within the agouti-related protein (AgRP) neurons of the hypothalamus. However, clinical studies indicate that leptin is undesirable as a therapeutic regiment for obesity, which is at least partly attributed to the poorly understood complex secondary structure and key signaling mechanism of the leptin-responsive neural circuit. Here, we show that the LepR-expressing portal neurons send GABAergic projections to a cohort of α3-GABAA receptor expressing neurons within the dorsomedial hypothalamic nucleus (DMH) for the control of leptin-mediated obesity phenotype. We identified the …

Asprosin Promotes Feeding Through Sk Channel-Dependent Activation Of Agrp Neurons, Bing Feng, Hesong Liu, Ila Mishra, Clemens Duerrschmid, Peiyu Gao, Pingwen Xu, Chunmei Wang, Yanlin He

Faculty, Staff and Students Publications

Asprosin, a recently identified adipokine, activates agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARH) via binding to protein tyrosine phosphatase receptor δ (Ptprd) to increase food intake. However, the intracellular mechanisms responsible for asprosin/Ptprd-mediated activation of AgRPARH neurons remain unknown. Here, we demonstrate that the small-conductance calcium-activated potassium (SK) channel is required for the stimulatory effects of asprosin/Ptprd on AgRPARH neurons. Specifically, we found that deficiency or elevation of circulating asprosin increased or decreased the SK current in AgRPARH neurons, respectively. AgRPARH-specific deletion of SK3 (an SK channel subtype highly expressed in AgRPARH neurons) blocked asprosin-induced …

Tfeb-Mediated Lysosomal Exocytosis Alleviates High-Fat Diet-Induced Lipotoxicity In The Kidney, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Satoshi Minami, Atsushi Takahashi, Jun Matsuda, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Isao Matsui, Takayuki Hamano, Masatomo Takahashi, Maiko Goto, Yoshihiro Izumi, Takeshi Bamba, Miwa Sasai, Masahiro Yamamoto, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Shuhei Nakamura, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney …

Randomized Controlled Trial Of A Novel Lifestyle Intervention Used With Or Without Meal Replacements In Work Sites, Sai Krupa Das, Rachel E Silver, Taylor A Vail, Meghan K Chin, Caroline M Blanchard, Stephanie L Dickinson, Xiwei Chen, Lisa Ceglia, Edward Saltzman, David B Allison, Susan B Roberts

Children’s Nutrition Research Center Staff Publications

Objective: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting.

Methods: Twelve work sites were randomized to an 18-month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6-month wait-listed control (n = 4). Participants were employees …

Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson

Faculty, Staff and Students Publications

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.

METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification …

Obesity Is Associated With Altered Tumor Metabolism In Metastatic Melanoma, Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Jun Li, Xiaogang Wu, Aditya K Mishra, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J Deberardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L Mcquade

Faculty, Staff and Student Publications

PURPOSE: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI).

EXPERIMENTAL DESIGN: Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371).

RESULTS: DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased …

The Rheumatoid Arthritis Drug Auranofin Lowers Leptin Levels And Exerts Antidiabetic Effects In Obese Mice, Aaron R Cox, Peter M Masschelin, Pradip K Saha, Jessica B Felix, Robert Sharp, Zeqin Lian, Yan Xia, Natasha Chernis, David A Bader, Kang Ho Kim, Xin Li, Jun Yoshino, Xin Li, Gang Li, Zheng Sun, Huaizhu Wu, Cristian Coarfa, David D Moore, Samuel Klein, Kai Sun, Sean M Hartig

Faculty, Staff and Student Publications

Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and coincides with type 2 diabetes mellitus (T2DM). However, pharmacological targeting of inflammation lacks durable therapeutic effects in insulin-resistant conditions. Through a computational screen, we discovered that the FDA-approved rheumatoid arthritis drug auranofin improved insulin sensitivity and normalized obesity-associated abnormalities, including hepatic steatosis and hyperinsulinemia in mouse models of T2DM. We also discovered that auranofin accumulation in WAT depleted inflammatory responses to a high-fat diet without altering body composition in obese wild-type mice. Surprisingly, elevated leptin levels and blunted beta-adrenergic receptor activity achieved by leptin receptor deletion abolished the antidiabetic …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …

Dawn-To-Dusk Dry Fasting Induces Anti-Atherosclerotic, Anti-Inflammatory, And Anti-Tumorigenic Proteome In Peripheral Blood Mononuclear Cells In Subjects With Metabolic Syndrome, Ayse L Mindikoglu, Jihwan Park, Antone R Opekun, Mustafa M Abdulsada, Zoe R Wilhelm, Prasun K Jalal, Sridevi Devaraj, Sung Yun Jung

Faculty, Staff and Students Publications

BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is associated with pro-inflammatory state, increased risk for atherosclerosis, and multiple cancers. Our previous results on subjects with metabolic syndrome showed that 4-week dawn-to-dusk (sunset) dry fasting resulted in significant changes in the serum proteome and improvement in several metabolic risk factors. Peripheral blood mononuclear cells (PBMC) proteomics is a powerful tool that can provide mechanistic insights into how dawn-to-dusk dry fasting affects protein expression in metabolic pathways at cellular level. In this study, we determined whether dawn-to-dusk …

Technology-Based Obesity Prevention Interventions Among Hispanic Adolescents In The United States: Scoping Review, Erica G Soltero, Callie Lopez, Edith Hernandez, Teresia M O'Connor, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: Given that today's adolescents are digital front-runners, technology-based obesity prevention strategies are age-appropriate for this population. The use of remote and wireless technologies may be suitable for extending the reach and engagement of obesity prevention efforts among high-risk Hispanic youths, as this subgroup is disproportionately affected by barriers that limit participation in traditional, in-person interventions.

Objective: The purpose of this scoping review was to examine the intervention and sample characteristics of technology-based obesity prevention interventions among Hispanic adolescents. We also examined feasibility criteria to assess the acceptability and appropriateness of technology-based strategies among Hispanic youths.

Methods: A comprehensive search …

The Role Of Kisspeptins In Trophoblast Cell Dynamics: Comparative Studies Using The Horse And The Preeclamptic-Like Bph/5 Mouse As Animal Models, Viviane Cristine Leite Gomes

LSU Doctoral Dissertations

Kisspeptins, a family of small peptides derived from the Kiss1 gene, have been described in trophoblast cell dynamics, placentation, and pregnancy outcomes. Furthermore, many other physiological functions have been attributed to kisspeptins, including neuroendocrine regulation of puberty and cyclicity, and peripheral and central regulation of metabolism and adipogenesis. Herein, studies were performed in the Blood Pressure High Subline 5 (BPH/5) mouse and the horse to further investigate the role of kisspeptins in pregnancy. The BPH/5 mouse recapitulates the main features of human preeclampsia (PE), a hypertensive disorder of pregnancy associated with maternal and fetal adverse outcomes. BPH/5 phenotypic characteristics include …

The Roles Of Sleep And Eating Patterns In Adiposity Gain Among Preschool-Aged Children, Amy R Goetz, Ishita Jindal, Jennette P Moreno, Maurice R Puyau, Anne L Adolph, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

BACKGROUND: Short sleep durations are related to risks for obesity in preschool children. However, the underlying mechanism or mechanisms are not clear.

OBJECTIVES: We evaluated the relationships between sleep characteristics and body composition, energetics, and weight-regulating behaviors in preschool-aged children, as well as the longitudinal associations between children's sleep and eating patterns and body composition at a 1-year follow-up.

METHODS: Data were drawn from a longitudinal study of 118 children aged 3-5 years. Sleep (duration, midpoint, regularity) and physical activity (PA) were measured by accelerometry over 6 consecutive days; total energy expenditure (TEE) was measured using the doubly labeled water …

Artificial Intelligence For Radiation Oncology Applications Using Public Datasets, Kareem A Wahid, Enrico Glerean, Jaakko Sahlsten, Joel Jaskari, Kimmo Kaski, Mohamed A Naser, Renjie He, Abdallah S R Mohamed, Clifton D Fuller

Faculty, Staff and Student Publications

Artificial intelligence (AI) has exceptional potential to positively impact the field of radiation oncology. However, large curated datasets - often involving imaging data and corresponding annotations - are required to develop radiation oncology AI models. Importantly, the recent establishment of Findable, Accessible, Interoperable, Reusable (FAIR) principles for scientific data management have enabled an increasing number of radiation oncology related datasets to be disseminated through data repositories, thereby acting as a rich source of data for AI model building. This manuscript reviews the current and future state of radiation oncology data dissemination, with a particular emphasis on published imaging datasets, AI …

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Faculty, Staff and Students Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

The Associations Between Relative And Absolute Body Mass Index With Mortality Rate Based On Predictions From Stigma Theory, Gregory Pavela, Nengjun Yi, Luis Mestre, Stella Lartey, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: The social consequences of obesity may influence health and mortality rate (MR), given obesity's status as a highly stigmatized condition. Hence, a high absolute body mass index (BMI) in conjunction with the stigmatization of a high BMI may each independently increase the rate of MR.

Objectives: We tested whether relative BMI, defined as ordinal rank within a social reference group jointly defined by age, sex, and race/ethnicity, is associated with MR independent of absolute BMI.

Methods: Data were from three nationally representative datasets: the Health and Retirement Study (n = 31,115), the National Health Interview Survey (NHIS, n = …

Re-Analysis And Additional Information Needed To Inform Conclusions Comment On Halenova Et Al Deuterium-Depleted Water As Adjuvant Therapeutic Agent For Treatment Of Diet-Induced Obesity In Rats, Colby J Vorland, Xiwei Chen, Daniella E Chusyd, Luis M Mestre, Stephanie L Dickinson, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

We were interested to read the report by Halenova et al. [...].

Characteristics Of Eating Behavior Profiles Among Preschoolers With Low-Income Backgrounds: A Person-Centered Analysis, Jennifer Orlet Fisher, Sheryl O Hughes, Alison L Miller, Mildred A Horodynski, Holly E Brophy-Herb, Dawn A Contreras, Niko Kaciroti, Karen E Peterson, Katherine L Rosenblum, Danielle Appugliese, Julie C Lumeng

Children’s Nutrition Research Center Staff Publications

Background: Individual differences in eating behaviors among young children are well-established, but the extent to which behaviors aggregate within individuals to form distinct eating behavior profiles remains unknown. Our objectives were to identify eating behavior profiles among preschool-aged children and evaluate associations with temperament and weight.

Methods: A secondary, cross-sectional analysis of baseline data from 2 cohort studies was conducted involving 1004 children aged 3-4 years and their parents with low-income backgrounds. Children's eating behaviors and temperament were assessed by parental report. Body mass index z-scores and weight status were calculated using measured heights and weights. Latent profile analysis (LPA) …

Activating Connexin43 Gap Junctions Primes Adipose Tissue For Therapeutic Intervention, Yi Zhu, Na Li, Mingyang Huang, Xi Chen, Yu A An, Jianping Li, Shangang Zhao, Jan-Bernd Funcke, Jianhong Cao, Zhenyan He, Qingzhang Zhu, Zhuzhen Zhang, Zhao V Wang, Lin Xu, Kevin W Williams, Chien Li, Kevin Grove, Philipp E Scherer

Faculty, Staff and Students Publications

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic …

Context Matters: Preliminary Evidence That The Association Between Positive Affect And Adiposity In Infancy Varies In Social Vs Non-Social Situations, Alexis C Wood, Shabnam R Momin, Mackenzie K Senn, David J Bridgett

Children’s Nutrition Research Center Staff Publications

Previous studies have suggested that infants high in negative affect have higher levels of adiposity, arising in part via changes in nutrition (e.g., “feeding to soothe”). Few studies have examined whether positive affect shows similar or inverse associations with adiposity. The current study examined cross-sectional and longitudinal relationships between adiposity and observations of positive affect in both a social and a non-social context, using data from infants at four (n = 125) and 12 (n = 80) months of age. Our analyses did not find any cross-sectional associations between positive affect and adiposity (all p > 0.05). However, in the longitudinal …

French-Fried Potato Consumption And Energy Balance: A Randomized Controlled Trial, Daniel L Smith, Rebecca L Hanson, Stephanie L Dickinson, Xiwei Chen, Amy M Goss, John B Cleek, W Timothy Garvey, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Epidemiologic observations suggest increased potato consumption correlates with weight gain, adiposity, and diabetes risk, whereas nut consumption is associated with weight control and metabolic health. Randomized controlled trial (RCT) data indicate humans respond to changes in energy intake in single dietary components and compensate for extra energy consumed.

Objectives: We completed an RCT testing whether increased daily potato consumption influences energy balance [specifically, fat mass (FM)] compared with calorie-matched almond consumption.

Methods: A 30-d RCT of 180 adults prescribed calorie-matched (300 kcal/d, n = 60 participants/group) than consumed 1 of the following: 1) almonds (almond group), 2) French fries …

The Hypothalamus For Whole-Body Physiology: From Metabolism To Aging, Tiemin Liu, Yong Xu, Chun-Xia Yi, Qingchun Tong, Dongsheng Cai

Children’s Nutrition Research Center Staff Publications

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing …

Co-Transmitting Neurons In The Lateral Septal Nucleus Exhibit Features Of Neurotransmitter Switching, Patrick J Hunt, Mikhail Kochukov, Brandon T Pekarek, Benjamin D W Belfort, Juan M Romero, Jessica L Swanson, Benjamin R Arenkiel

Faculty, Staff and Students Publications

The lateral septal nucleus (LSN) is a highly interconnected region of the central brain whose activity regulates widespread circuitry. As such, the mechanisms that govern neuronal activity within the LSN have far-reaching implications on numerous brain-wide nuclei, circuits, and behaviors. We found that GABAergic neurons within the LSN express markers that mediate the release of acetylcholine (ACh). Moreover, we show that these vGATLSN neurons release both GABA and ACh onto local glutamatergic LSN neurons. Using both short-term and long-term neuronal labeling techniques we observed expression of the cholinergic neuron marker Choline Acetyltransferase (ChAT) in vGATLSN neurons. These findings provide evidence …

Reno-Protective And Immune Effects Of Growth Differentiation Factor 15 In Obesity-Related Kidney Disease, Jessie T. Sullivan

Honors Thesis

According to the World Health Organization, worldwide obesity has tripled since 1975 and is still on the rise, putting people at a higher risk of some cardiovascular diseases and kidney disease. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied recently for its role in multiple biological processes and diseases. The member of the transforming growth factor beta (TGF-b) family has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases, stroke, diabetes, osteoarthritis, cancer, and kidney disease. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have …

Protein Tyrosine Phosphatase Receptor Δ Serves As The Orexigenic Asprosin Receptor, Ila Mishra, Wei Rose Xie, Juan C Bournat, Yang He, Chunmei Wang, Elizabeth Sabath Silva, Hailan Liu, Zhiqiang Ku, Yinghua Chen, Bernadette O Erokwu, Peilin Jia, Zhongming Zhao, Zhiqiang An, Chris A Flask, Yanlin He, Yong Xu, Atul R Chopra

Faculty, Staff and Student Publications

Asprosin is a fasting-induced glucogenic and centrally acting orexigenic hormone. The olfactory receptor Olfr734 is known to be the hepatic receptor for asprosin that mediates its effects on glucose production, but the receptor for asprosin's orexigenic function has been unclear. Here, we have identified protein tyrosine phosphatase receptor δ (Ptprd) as the orexigenic receptor for asprosin. Asprosin functions as a high-affinity Ptprd ligand in hypothalamic AgRP neurons, regulating the activity of this circuit in a cell-autonomous manner. Genetic ablation of Ptprd results in a strong loss of appetite, leanness, and an inability to respond to the orexigenic effects of asprosin. …

Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background:

Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO).

Objective:

We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics.

Patients/Design:

Youth (n=188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting …