Paul Kievit, Ph.D.
- Associate Professor, Oregon National Primate Research Center
Biography
Childhood obesity rates are at their highest recorded level of 18.5%, putting approximately 14 million young children and adolescents at risk for poor health for the remainder of their life. Obesity not only impacts the quality of life, but also increases risk factors for life-threatening disease late life, including type 2 diabetes, cardiovascular disease and cancer. Understanding how maternal health and nutrition can impact development during all stages of early life can provide insights into the pathophysiology of childhood obesity. It is our belief that studying these complicated, highly integrative pathways can result in discovering ways to improve the health of both mother and baby and interrupt this vicious cycle of obesity.
Dr. Kievit is the Interim Chief and an Associate Professor in the Division of Metabolic Health & Disease at ONPRC and his laboratory has several areas of interest with an overall focus on the impact of obesity and energy homeostasis on human health, as well as understanding how particular therapies can intervene. A diverse and highly motivated team investigates areas such as the impact of maternal obesity on the developing metabolic systems. These studies focus on changes within the central nervous system neurocircuitry and correlated changes in the periphery such as pancreas function, inflammation and gastrointestinal pathways. We utilize a large variety of models and techniques in an attempt to study the full spectrum of the disease. This includes the use of both rodent and nonhuman primate models and techniques investigating whole body physiology (energy expenditure, food intake behavior) as well as changes at the organ level (immunohistochemistry, in-situ/RNAscope) and molecular/cellular level (electrophysiology, RNA-seq, islet ex-vivo perifusion analysis). We further engage in collaborative research with partners from both academic and industry, studying novel therapeutics to assist with weight loss or diabetes and have an extensive program that is geared towards understanding the reciprocal relationship between infectious disease and metabolism. There is an increased awareness that the immune system plays a critical role in various physiological processes beyond its classical pathogen control activity, including metabolic pathways such as body weight and glucose homeostasis. Our laboratory is interested in understanding how infectious agents like SARS-CoV-2 can impact metabolism.
Dr. Paul Kievit received his Msc in Toxicology from Leiden University in Leiden, his Ph.D. in Cell and Developmental Biology from Oregon Health and Science University (OHSU) and received postdoctoral training at Beth Israel Deaconess Medical Center/Harvard Medical School and OHSU.
Publications
Selected publications
- Rangwala SM, D'Aquino K, Zhang YM, Bader L, Edwards W, Zheng S, Eckardt A, Lacombe A, Pick R, Moreno V, Kang L, Jian W, Arnoult E, Case M, Jenkinson C, Chi E, Swanson RV, Kievit P, Grove K, Macielag M, Erion MD, SinhaRoy R, Leonard JN. A Long-Acting PYY3-36 Analog Mediates Robust Anorectic Efficacy with Minimal Emesis in Nonhuman Primates. Cell Metab. 2019 Feb 11
- Andersen B, Straarup EM, Heppner KM, Takahashi DL, Raffaele V, Dissen GA, Lewandowski K, Bödvarsdottir TB, Raun K, Grove KL, Kievit P. FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys.Int J Obes (Lond). 2018 Jun;42(6):1151-1160
- True C, Arik A, Lindsley S, Kirigiti M, Sullivan E, Kievit P. Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates. Front Endocrinol (Lausanne). 2018 Sep 10;9:508
- True C, Dean T, Takahashi D, Sullivan E, Kievit P. Maternal High-Fat Diet Effects on Adaptations to Metabolic Challenges in Male and Female Juvenile Nonhuman Primates. Obesity (Silver Spring). 2018 Sep;26(9):1430-1438
- Kievit, P; Halem, H; Marks, DL; Dong, JZ; Glavas, MM; Sinnayah, P; Pranger, L; Cowley, MA; Grove, KL; Culler, MD. 2013. Chronic treatment with a melanocortin 4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques*. Diabetes. 62: 490-7. *Highlighted in Nature Reviews
Publications
Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques
Liver InternationalActivation of coagulation FXI promotes endothelial inflammation and amplifies platelet activation in a nonhuman primate model of hyperlipidemia
Research and Practice in Thrombosis and HaemostasisAnalysis of beta-cell maturity and mitochondrial morphology in juvenile non-human primates exposed to maternal Western-style diet during development
Frontiers in EndocrinologyEffect of metabolic status on response to SIV infection and antiretroviral therapy in nonhuman primates
JCI InsightHypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques
Nature biotechnologyHypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate
Cell Stem CellInitiation of metformin in early pregnancy results in fetal bioaccumulation, growth restriction, and renal dysmorphology in a primate model
American journal of obstetrics and gynecologyNK2R control of energy expenditure and feeding to treat metabolic diseases
NaturePreparation of Frozen Non-Human Primate Fetal Islets for Combined Single Nuclei RNA-Sequencing and ATAC-Sequencing, and Bulk Metabolomics
Journal of visualized experiments : JoVEA Maternal Western-Style Diet Impairs Skeletal Muscle Lipid Metabolism in Adolescent Japanese Macaques
DiabetesEffect of antiplatelet agents and tyrosine kinase inhibitors on oxLDL-mediated procoagulant platelet activity
Blood AdvancesGlial, Neuronal, Vascular, Retinal Pigment Epithelium, and Inflammatory Cell Damage in a New Western Diet–Induced Primate Model of Diabetic Retinopathy
American Journal of PathologyMaternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring
Cell ReportsMaternal Western diet is associated with distinct preclinical pediatric NAFLD phenotypes in juvenile nonhuman primate offspring
Hepatology CommunicationsMaternal Western-style diet in nonhuman primates leads to offspring islet adaptations including altered gene expression and insulin hypersecretion
American Journal of Physiology - Endocrinology and MetabolismMetformin Disrupts Signaling and Metabolism in Fetal Hepatocytes
DiabetesSuppression of food intake by glp1r/lepr-coexpressing neurons prevents obesity in mouse models
Journal of Clinical InvestigationBedding as an Enrichment Strategy in Group-housed Mauritian Cynomolgus Macaques (Macaca fascicularis)
Journal of the American Association for Laboratory Animal ScienceDipeptidyl peptidase IV inhibition delays developmental programming of obesity and metabolic disease in male offspring of obese mothers
Journal of Developmental Origins of Health and DiseaseIbrutinib Inhibits BMX-Dependent Endothelial VCAM-1 Expression In Vitro and Pro-Atherosclerotic Endothelial Activation and Platelet Adhesion In Vivo
Cellular and Molecular BioengineeringArterial platelet adhesion in atherosclerosis-prone arteries of obese, insulin-resistant nonhuman primates
Journal of the American Heart AssociationCross-species analysis defines the conservation of anatomically segregated VMH neuron populations
eLifeFibroblast Growth Factor-1 Activates Neurons in the Arcuate Nucleus and Dorsal Vagal Complex
Frontiers in EndocrinologyMaternal Western diet exposure increases periportal fibrosis beginning in utero in nonhuman primate offspring
JCI InsightShort-term Western-style diet negatively impacts reproductive outcomes in primates
JCI InsightWestern-style diet consumption impairs maternal insulin sensitivity and glucose metabolism during pregnancy in a Japanese macaque model
Scientific ReportsEffects of pre- And postnatal protein restriction on maternal and offspring metabolism in the nonhuman primate
American Journal of Physiology - Regulatory Integrative and Comparative PhysiologyEndocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass
Cell ReportsLeptin modulates pancreatic β-cell membrane potential through Src kinase-mediated phosphorylation of NMDA receptors
Journal of Biological ChemistryMaternal obesity and western-style diet impair fetal and juvenile offspring skeletal muscle insulin-stimulated glucose transport in nonhuman primates
Diabetes