Oncotarget

Research Papers:

P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions

Tatiana Halenova, Oleksii Savchuk, Ludmila Ostapchenko, Andrey Chursov, Nathan Fridlyand, Andrey B. Komissarov, Franco Venanzi, Sergey I. Kolesnikov, Albert A. Sufianov, Michael Y. Sherman, Vladimir L. Gabai, _ Alexander M. Shneider

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Abstract

Tatiana Halenova1, Oleksii Savchuk1, Ludmila Ostapchenko1, Andrey Chursov2, Nathan Fridlyand3, Andrey B. Komissarov4, Franco Venanzi3, Sergey I. Kolesnikov5,6,7, Albert A. Sufianov8,9, Michael Y. Sherman10, Vladimir L. Gabai2,10 and Alexander M. Shneider2,9,11

1Educational and Scientific Center ‘Institute of Biology and Medicine’, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine

2Curelab Oncology Inc, Dedham, MA, USA

3School of Biosciences, University of Camerino, Camerino, Italy

4Research Institute of Influenza, St-Petersburg, Russia

5Russian Academy of Sciences, Moscow, Russia

6Lomonosov Moscow State University, Moscow, Russia

7Research Center of Family Health and Reproduction Problems, Irkutsk, Russia

8Federal Center of Neurosurgery, Tyumen, Russia

9Sechenov First Moscow State Medical University, Moscow, Russia

10Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA

11Department 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.

Author Information

Tatiana Halenova

Oleksii Savchuk

Ludmila Ostapchenko

Andrey Chursov

Nathan Fridlyand

Andrey B. Komissarov

Franco Venanzi

Sergey I. Kolesnikov

Albert A. Sufianov

Michael Y. Sherman

Vladimir L. Gabai
Primary Contact  _

Alexander M. Shneider


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