P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions
| Autor: | Vladimir L. Gabai, Oleksii Savchuk, Alexander M. Shneider, Michael Y. Sherman, Sergey I. Kolesnikov, Franco M. Venanzi, Andrey Chursov, Ludmila Ostapchenko, Nathan Fridlyand, Albert Sufianov, Tatiana Halenova, Andrey Komissarov |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Food consumption 03 medical and health sciences 0302 clinical medicine Plasmid Diabetes mellitus Internal medicine Shevchenko Medicine diabetes business.industry Insulin medicine.disease Obesity cytokines serotonin 030104 developmental biology Endocrinology Oncology inflammation Federal Center of Neurosurgery Immunology high-calorie diet business Body mass index 030217 neurology & neurosurgery Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Tatiana Halenova 1 , Oleksii Savchuk 1 , Ludmila Ostapchenko 1 , Andrey Chursov 2 , Nathan Fridlyand 3 , Andrey B. Komissarov 4 , Franco Venanzi 3 , Sergey I. Kolesnikov 5, 6, 7 , Albert A. Sufianov 8, 9 , Michael Y. Sherman 10 , Vladimir L. Gabai 2, 10 and Alexander M. Shneider 2, 9, 11 1 Educational and Scientific Center ‘Institute of Biology and Medicine’, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine 2 Curelab Oncology Inc, Dedham, MA, USA 3 School of Biosciences, University of Camerino, Camerino, Italy 4 Research Institute of Influenza, St-Petersburg, Russia 5 Russian Academy of Sciences, Moscow, Russia 6 Lomonosov Moscow State University, Moscow, Russia 7 Research Center of Family Health and Reproduction Problems, Irkutsk, Russia 8 Federal Center of Neurosurgery, Tyumen, Russia 9 Sechenov First Moscow State Medical University, Moscow, Russia 10 Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA 11 Department of Molecular Biology, Ariel University, Ariel, Israel Correspondence to: Vladimir L. Gabai, email: vgabai@curelab.com Alexander M. Shneider, email: ashneider@curelab.com Keywords: diabetes, high-calorie diet, inflammation, cytokines, serotonin Received: May 23, 2017 Accepted: June 26, 2017 Published: August 03, 2017 ABSTRACT A high-calorie diet (HCD) induces two mutually exacerbating effects contributing to diet-induced obesity (DIO): impaired glucose metabolism and increased food consumption. A link between the metabolic and behavioral manifestations is not well understood yet. We hypothesized that chronic inflammation induced by HCD plays a key role in linking together the two components of diet-induced pathology. Based on this hypothesis, we tested if a plasmid (DNA vaccine) encoding p62 (SQSTM1) would alleviate DIO including its metabolic and/or food consumption abnormalities. Previously we reported that injections of the p62 plasmid reduce chronic inflammation during ovariectomy-induced osteoporosis. Here we found that the p62 plasmid reduced levels of pro-inflammatory cytokines IL-1β, IL-12, and INFγ and increased levels of anti-inflammatory cytokines IL-4, IL-10 and TGFβ in HCD-fed animals. Due to this anti-inflammatory response, we further tested whether the plasmid can alleviate HCD-induced obesity and associated metabolic and feeding impairments. Indeed, p62 plasmid significantly reversed effects of HCD on the body mass index (BMI), levels of glucose, insulin and glycosylated hemoglobin (HbA1c). Furthermore, p62 plasmid partially restored levels of the satiety hormone, serotonin, and tryptophan, simultaneously reducing activity of monoamine oxidase (MAO) in the brain affected by the HCD. Finally, the plasmid partially reversed increased food consumption caused by HCD. Therefore, the administering of p62 plasmid alleviates both metabolic and behavioral components of HCD-induced obesity. |
| Databáze: | OpenAIRE |
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