Metabolomics Enables Precision Medicine: “A White Paper, Community Perspective”, Richard D. Beger, Warwick B. Dunn, Michael A. Schmidt, Steven S. Cross, Jennifer A. Kirwan, Marta S. Cascante, Lorraine Brennan, David S. Wishart, Matej Orešič, Thomas Hankemeier, David Broadhurst, Andrew N. Lane, Karsten Suhre, Gabi Kastenmüller, Susan J. Sumner, Ines Thiele, Oliver E. Fiehn, Rima Kaddurah- Daouk

Research outputs 2014 to 2021

Introduction:Background to metabolomics:

Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or “-omics” level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person’s metabolic state provides a close representation of that individual’s overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides …

Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff

USF Tampa Graduate Theses and Dissertations

PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver. …

Effects Of Prenatal Environment Are Revealed By Post-Natal Challenges: Embryonic Hormone Exposure, Adrenocortical Function And Food In Seabird Chicks, Z. Morgan Benowitz-Fredericks, Jannik Schultner, Alexander S. Kitaysky

Faculty Journal Articles

The interaction between prenatal environments and postnatal environments is an important source of phenotypic variability. We examined the ability of prenatal steroid exposure and postnatal energy restriction to explain adrenocortical function and fledging age in captive seabird chicks. We proposed and tested two hypotheses: (1) the strength of prenatal effects is attenuated by challenging postnatal environments (postnatal override) and (2) the strength of prenatal effects increases with the severity of postnatal challenges (postnatal reveal). We reared common murre (Uria aalge) chicks and measured prenatal exposure to corticosterone (CORT) and testosterone (T) from allantoic waste. Adrenocortical function was assessed after 10 …

Regulation Of Thyroid Hormone-Induced Development In Vivo By Thyroid Hormone Transporters And Cytosolic Binding Proteins, Jinyoung Choi, Christine L. Moskalik, Allison Ng, Stephen F. Matter, Daniel R. Buchholz

Publications & Research

Differential tissue sensitivity/responsivity to hormones can explain developmental asynchrony among hormone-dependent events despite equivalent exposure of each tissue to circulating hormone levels. A dramatic vertebrate example is during frog metamorphosis, where transformation of the hind limb, brain, intestine, liver, and tail are completely dependent on thyroid hormone (TH) but occurs asynchronously during development. TH transporters (THTs) and cytosolic TH binding proteins (CTHBPs) have been proposed to affect the timing of tissue transformation based on expression profiles and in vitro studies, but they have not been previously tested in vivo. We used a combination of expression pattern, relative expression level, …

Lh-Independent Testosterone Secretion Is Mediated By The Interaction Between Gnrh2 And Its Receptor Within Porcine Testes, Amy T. Desaulniers, Rebecca A. Cederberg, Ginger A. Mills, J. Joe Ford, Clay A. Lents, Brett R. White

Department of Animal Science: Faculty Publications

Unlike classic gonadotropin-releasing hormone 1 (GNRH1), the second mammalian isoform (GNRH2) is an ineffective stimulant of gonadotropin release. Species that produce GNRH2 may not maintain a functional GNRH2 receptor (GNRHR2) due to coding errors. A full-length GNRHR2 gene has been identified in swine, but its role in reproduction requires further elucidation. Our objective was to examine the role of GNRH2 and GNRHR2 in testicular function of boars. We discovered that GNRH2 levels were higher in the testis than in the anterior pituitary gland or hypothalamus, corresponding to greater GNRHR2 abundance in the testis versus the anterior pituitary gland. Moreover, GNRH2 …

Estrogen Receptor–Α In Medial Amygdala Neurons Regulates Body Weight, Pingwen Xu, Xuehong Cao, Yanlin He, Liangru Zhu, Yongjie Yang, Kenji Saito, Chunmei Wang, Xiaofeng Yan, Antentor Othrell Hinton Jr., Fang Zou, Hongfang Ding, Yan Xia, Chunling Yan, Gang Shu, San-Pin Wu, Bin Yang, Benjamin Feng, Deborah J. Clegg, Richard Demarchi, Sohaib A. Khan, Sophia Y. Tsai, Francesco J. Demayo, Qi Wu, Qingchun Tong, Yong Xu

Peer Reviewed Articles

Estrogen receptor–α (ERα) activity in the brain prevents obesity in both males and females. However, the ERα-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded–1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels of ERα. Specific deletion of the gene encoding ERα (Esr1) from SIM1 neurons, which are mostly within the MeA, caused hypoactivity and obesity in both male and female mice fed with regular chow, increased susceptibility to diet-induced obesity (DIO) in males but not in females, and blunted the body weight–lowering effects of a glucagon-like peptide-1–estrogen …

The Effects Of Arginine Vasopressin On Maternal Behavior And Aggression In Peromyscus Californicus Mothers, Nathaniel Ng

Honors Projects

Research studies since the 1950s have shown that a chemical within the brain called arginine vasopressin (AVP) is associated with the modulation of many different social behaviors in mammals. Some of these behaviors are related to parenting, such as parental care initiation, aggression, social recognition, depression and anxiety. Understanding the physiology behind AVP regulation could allow for the creation of new therapies for treating human social disorders, such as using an AVP receptor antagonist to attenuate anxiety. This project examines how neural injections of AVP and an AVP receptor antagonist affect both maternal care and aggression in female Peromyscus californicus …

Immunolocalization Of G Protein-Coupled Estrogen Receptor In The Rat Epididymis, Griselle B. Martinez-Traverso, Christopher Pearl

Peer Reviewed Articles

Background

Estrogen plays an important role in male reproduction, and males lacking estrogen signaling in the reproductive tissues are infertile. Estrogen signaling is mediated via two nuclear receptors, ERα and ERβ, but it was recently found that a G protein-coupled estrogen receptor (GPER) is present in the testis. It is believed that GPER is a membrane form of the estrogen receptor and mediates non-classical estrogen signaling. However, the cellular localization of GPER in the epididymis is unknown. Therefore, the objective of this study was to determine the cellular and regional expression of GPER in the rat epididymis.

Findings

To localize …

The Effect Of Run Sprint Interval Training On Diabetic Metabolic Markers In Prediabetic Adults, Kathryn L. Hilovsky

Masters Theses, 2010-2019

Abstract

Purpose: The primary purpose of this study was to compare the effects of an 8-week run-sprint interval training (R-SIT) and continuous moderate-intensity training (MIT) on fasting blood glucose, HbA1c, insulin sensitivity, and β-cell function in sedentary, prediabetic adults. Secondary outcomes of the study included anthropometric, body composition variables, and aerobic capacity.

Methods: Sedentary, physician diagnosed prediabetic individuals were randomized into R-SIT (n=7, BMI 36.76 ± 9.79) or MIT (n=8, BMI 40.59 ± 12.49) interventions. Subjects participated in supervised exercise three times a week and attended a Diabetes Prevention Program course, once weekly. R-SIT participants performed 4-6 x 30-second …

The Role Of Rfamide-Related Peptide 3 (Rfrp3) In Regulation Of The Neuroendocrine Reproductive And Growth Axes Of The Boar, Jennifer F. Thorson, Amy T. Desaulniers, Chanho Lee, Brett R. White, J. Joe Ford, Clay A. Lents

Department of Animal Science: Faculty Publications

RFamide-related peptide 3 (RFRP3) has been implicated in regulating reproduction and growth. This regulation appears to be dependent upon sex, species, physiological status, and developmental stage. The objective of the present study was to evaluate the effects of RFRP3 on circulating concentrations of luteinizing hormone (LH) and growth hormone (GH) in mature boars. The hypothesis was RFRP3 would reduce circulating concentrations of LH and increase concentrations of GH. Meishan boars (716.6±2.8 days of age; 125.0±12.4kg BW) were randomly assigned to treatment: saline (n=4) or RFRP3 (8.5mg; n=5). Plasma was collected at 15-min intervals during 3 periods: pre-treatment, treatment, and post-treatment. …

The Proteomic Response In The Crustacean Molting Gland Of Land Crab Gecarcinus Lateralis In Response To Artificially Induced Molting Throughout Its Molting Cycle., Andrea Reider, Talia B. Head, Lars Tomanek, Donald L. Mykles

STAR Program Research Presentations

Molting in crustaceans is a highly complex physiological process involving negative regulation by two paired endocrine glands, the X-organ/sinus gland complex (XO/SG) and the Y-organ (YO). The XO/SG complex is responsible for making molt-inhibiting hormone (MIH) which negatively regulates synthesis of molting hormones (ecdysteroids) by the YO. Eyestalk ablation (ESA) removes the source of MIH and provides an experimental means to manipulate and induce molting, although the physiological effects of ESA on the YO have not been fully characterized. Analysis of gene expression in the XOs and YOs has lead to the development of a proposed molecular signaling pathway which …

Sea Turtle Hatchling Sex Ratios Determined Via Hormone Assay: Implications Of Climate Change?, William A. Hilton, Matthew Godfrey, Camryn D. Allen

STAR Program Research Presentations

Currently all species of sea turtles are listed as threatened or endangered with extinction under the U.S. Endangered Species Act. Due to their status, sea turtle conservation is a high priority for the U.S. National Marine Fisheries Service and U.S. Fish and Wildlife Service. One major challenge conservationists face is the lack of a noninvasive, cost efficient method for determining the sex of hatchling sea turtles. Because secondary sex characteristics (i.e. males have longer tails) are not evident until turtles start to reach sexual maturity, the sex of hatchlings is not easily determined. The least invasive way to determine the …

Effect Of The Acute Stress Response On Foraging Behavior In Mountain White-Crowned Sparrows, Zonotrichia Leucophrys, Sarah C. Osborne

Scripps Senior Theses

Free-living vertebrates likely encounter many stressors throughout their lifetime, from fighting off a predator to coping with unpredictable weather. As a result, vertebrates will mount an acute response to the stressors. Here, we outline previous research conducted in behavioral endocrinology and stress physiology as it relates to our research. We then discuss our study with white-crowned sparrows (Zonotrichia leucophrys) in Tioga Pass Meadow, in which we examined how the acute stress response affects foraging behavior 24 hours after a stressor. In birds that underwent a stress series, we found there to be a significant 57% decrease in foraging …

Awareness Of Diabetes Risk Associated With Individuals 18 And Older, Rebecca Jane Boone

Walden Dissertations and Doctoral Studies

The risk of developing Type 2 diabetes is increasing at epidemic proportions, and is 12-17% higher in Marion County Florida than it is across the state, based on Florida Department of Health statistics. The purpose of this DNP project was to determine if awareness of individual risk of developing Type 2 diabetes through a questionnaire would result in high-risk participants agreeing to attend a diabetes prevention program (DPP) at a local medical clinic. The health belief model and Rosswurm and Larrabee's model for change were used as frameworks. The review of the literature showed that prevention programs were highly effective …

Mechanisms Of Estrogen Receptor Alternative Splicing And The Consequences For Aging In The Female Brain, Cody Lee Shults

Dissertations

The advances in healthcare and scientific knowledge have resulted in longer life expectancies in women. These advanced ages in women now means that they are experiencing the effects of age-related changes in the body for much longer periods of time, mainly reproductive senescence, resulting in the loss of circulating ovarian hormones. The age at which menopause occurs has not changed, resulting in women now living over a third of their lives in a postmenopausal state.

The major circulating estrogen produced by the ovaries, 17β-estradiol (E2), has many homeostatic effects in the body like neuroprotection and cardioprotection. Hormone replacement therapy (HT) …

Development Of Neuroendocrine Components Of The Thyroid Axis In The Direct-Developing Frog Eleutherodactylus Coqui: Formation Of The Median Eminence And Onset Of Pituitary Tsh Production., David H. Jennings, Bryce Evans, James Hanken

SIUE Faculty Research, Scholarship, and Creative Activity

Direct-developing frogs lack, wholly or in part, a wide range of larval features found in metamorphosing species and form adult-specific features precociously, during embryogenesis. Most information on thyroid regulation of direct development relies on hormone manipulations; the ontogeny of many thyroid axis components has not been fully described. This analysis examines differentiation of the median eminence of the hypothalamus and production of thyroid-stimulating hormone (TSH) by the pituitary of the direct-developing frog Eleutherodactylus coqui. The median eminence is established two-thirds of the way through embryogenesis. Cells immunoreactive to human TSHb antibodies are first detected during embryogenesis and quantitative changes in …

The Reproductive Biology Of The Finetooth Shark, Carcharhinus Isodon, In The Northwest Atlantic Ocean, Amanda N. Brown

UNF Graduate Theses and Dissertations

Shark fisheries are a multimillion dollar industry in the United States and have significant contributions both recreationally and commercially. In order to maintain this industry, fisheries must be properly managed. An understanding of life history and reproduction is crucial in order to adequately manage shark fisheries. The finetooth shark, Carcharhinus isodon, is a member of the small coastal shark (SCS) fishery complex. It is found in Atlantic waters from South Carolina to Florida and throughout the Gulf of Mexico. This species has recently come under increased fishing pressure and has previously been overfished. New data is needed in order …

Temporal Localization Of Insulin-Like Growth Factor 1 (Igf1) Positive Cells In Developing Hypothyroid Brain, Shelby Anne Kline

All Graduate Theses, Dissertations, and Other Capstone Projects

Hypothyroidism has been known to result in numerous neuroanatomical defects in the developing brain. To investigate further into the mechanism in which these defects are obtained, local brain insulin-like growth factor 1 (Igf1) was investigated in relation to the hypothyroid brain. There are many similarities between hypothyroidism and the Igf1 deficient brain. Additionally, TH (thyroid hormone) is known to interact with Igf1. Therefore, the purpose of this study was to investigate the effect of induced congenital hypothyroidism on the temporal expression of Igf1-positive cells in the brain. To investigate the relationship between TH and Igf1 in the brain, we inhibited …

The Effects Of Hibernation On The Hemostatic Properties Of The American Bullfrog, Rana Catesbeiana, Kiana Cullinan

Honors Program Theses

It is known that hibernating animals display a drastic reduction in metabolic rate, accompanied by reduced heart rate and rate of blood flow through vessels. Sluggish blood flow increases the risk for developing clots, yet it has been observed that hibernators conclusively display elongated clotting times. This observed impairment may be caused by the decrease in body temperature, due to a negative impact on the functioning of the enzymes involved in coagulation. Some hibernating endotherms, or “warm-blooded” animals, employ biological mechanisms as preventative means to prevent clotting during hibernation, such as the down-regulation of certain clotting factors or the production …

Crebh, A Novel Liver Clock Keeper For Energy Metabolism, Ze Zheng

Wayne State University Dissertations

Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Cyclic AMP responsive element binding protein 3-like 3 (CREB3L3, also known as CREBH) is a liver-enriched, endoplasmic reticulum (ER)-tethered transcription factor known to regulate hepatic acute-phase response and energy homeostasis under stress conditions. Here, we demonstrate that CREBH is regulated by the circadian clock and functions as a diurnal regulator of hepatic lipid and glucose metabolism. CREBH is required to maintain circadian profiles of blood triglycerides, fatty acids, and glucose as well as hepatic glycogen storage. CREBH rhythmically regulates expression levels and amplitudes …