Petite Integration Factor 1 (PIF1) helicase deficiency increases weight gain in Western diet-fed female mice without increased inflammatory markers or decreased glucose clearance
| Autor: | Lea Harrington, Yingze Zhang, Yanxia Chu, Sylvie Bannwarth, Ian Sipula, Robert M. O'Doherty, Sruti Shiva, Nikita Desai, Frances Belmonte, Véronique Paquis-Flucklinger, Michael J. Jurczak, Brett A. Kaufman, Nikolaos Dedousis, Aatur D. Singhi |
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| Přispěvatelé: | Division of Cardiology [Pittsburgh, PA, États-Unis], Center for Metabolism and Mitochondrial Medicine [Pittsburgh, PA, États-Unis] (C3M), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE)-University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Medicine [Pittsburgh, PA, États-Unis], Division of Endocrinology and Metabolism [Pittsburgh, PA, États-Unis], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE)-University of Pittsburgh (PITT), Department of Pathology [Pittsburgh, PA, États-Unis], Pittsburgh Liver Research Center [Pittsburgh, PA, États-Unis] (PLRC), Division of Pulmonary, Allergy and Critical Care Medicine [Pittsburgh, PA, États-Unis], Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM), BAK was supported by NIGMS (R01GM110424). RMO was supported by NIDDK (R01DK102839) and the Center for Metabolism and Mitochondrial Medicine (C3M) funding. FB was supported by NIDDK (T32DK007052) and the animal costs were supported by NIGMS and Stimulating Pittsburgh Research in Geroscience (SPRIG) Award. ND was supported by C3M. ADS was supported by Pittsburgh Liver Research Center (PLRC)., Université Nice Sophia Antipolis (1965 - 2019) (UNS), Bodescot, Myriam |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Physiology Adipose tissue [SDV.GEN] Life Sciences [q-bio]/Genetics Weight Gain Pathology and Laboratory Medicine Biochemistry Mice 0302 clinical medicine Medicine and Health Sciences Glucose homeostasis Immune Response Energy-Producing Organelles Mice Knockout [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Multidisciplinary Liver Diseases Fatty liver [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Mitochondrial DNA Mitochondria Nucleic acids Cholesterol Adipose Tissue Liver Physiological Parameters Body Composition Cytokines Medicine Female Inflammation Mediators Cellular Structures and Organelles medicine.symptom Research Article medicine.medical_specialty Forms of DNA Science Immunology Blood sugar 030209 endocrinology & metabolism Gastroenterology and Hepatology Motor Activity Bioenergetics Biology 03 medical and health sciences Signs and Symptoms Diagnostic Medicine Internal medicine Genetics medicine Animals Obesity Inflammation [SDV.GEN]Life Sciences [q-bio]/Genetics Biological Locomotion Body Weight DNA Helicases Biology and Life Sciences Cell Biology DNA Glucose Tolerance Test medicine.disease Fatty Liver [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition Glucose 030104 developmental biology Endocrinology Blood chemistry Diet Western Steatosis Energy Metabolism [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition Weight gain Homeostasis |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2019, 14 (5), pp.e0203101. ⟨10.1371/journal.pone.0203101⟩ PLoS ONE, Vol 14, Iss 5, p e0203101 (2019) PLoS ONE, 2019, 14 (5), pp.e0203101. ⟨10.1371/journal.pone.0203101⟩ |
| ISSN: | 1932-6203 |
| Popis: | International audience; Petite Integration Factor 1 (PIF1) is a multifunctional helicase present in nuclei and mitochondria. PIF1 knock out (KO) mice exhibit accelerated weight gain and decreased wheel running on a normal chow diet. In the current study, we investigated whether Pif1 ablation alters whole body metabolism in response to weight gain. PIF1 KO and wild type (WT) C57BL/6J mice were fed a Western diet (WD) rich in fat and carbohydrates before evaluation of their metabolic phenotype. Compared with weight gain-resistant WT female mice, WD-fed PIF1 KO females, but not males, showed accelerated adipose deposition, decreased locomotor activity, and reduced whole-body energy expenditure without increased dietary intake. Surprisingly, PIF1 KO females did not show obesity-induced alterations in fasting blood glucose and glucose clearance. WD-fed PIF1 KO females developed mild hepatic steatosis and associated changes in liver gene expression that were absent in weight-matched, WD-fed female controls, linking hepatic steatosis to Pif1 ablation rather than increased body weight. WD-fed PIF1 KO females also showed decreased expression of inflammation-associated genes in adipose tissue. Collectively, these data separated weight gain from inflammation and impaired glucose homeostasis. They also support a role for Pif1 in weight gain resistance and liver metabolic dysregulation during nutrient stress. |
| Databáze: | OpenAIRE |
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