Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Upregulated with Therapeutic Fasting in Humans and Diet Fat Withdrawal in Obese Mice

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Galli , E , Rossi , J , Neumann , T , Andressoo , J-O , Drinda , S & Lindholm , P 2019 , ' Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Upregulated with Therapeutic Fasting in Humans and Diet Fat Withdrawal in Obese Mice ' , Scientific Reports , vol. 9 , 14318 . https://doi.org/10.1038/s41598-019-50841-6

Title: Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Upregulated with Therapeutic Fasting in Humans and Diet Fat Withdrawal in Obese Mice
Author: Galli, Emilia; Rossi, Jari; Neumann, Thomas; Andressoo, Jaan-Olle; Drinda, Stefan; Lindholm, Päivi
Contributor organization: Institute of Biotechnology
Division of Pharmaceutical Biosciences
Helsinki Institute of Life Science HiLIFE, Joint Activities
University of Helsinki
Staff Services
Medicum
Department of Anatomy
Faculty of Medicine
University Management
Department of Pharmacology
Date: 2019-10-04
Language: eng
Number of pages: 12
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-019-50841-6
URI: http://hdl.handle.net/10138/306803
Abstract: Dietary restriction induces beneficial metabolic changes and prevents age-related deterioration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effects on cells in various models of degenerative diseases. Here we studied whether circulating concentrations of MANF are associated with fasting-induced positive effects. We quantified the levels of circulating MANF from 40 human subjects before and after therapeutic fasting. As measured by an enzyme-linked immunosorbent assay (ELISA), the mean concentration of plasma MANF increased after an average fasting of 15 days. Plasma MANF levels correlated inversely with adiponectin, a hormone that regulates metabolism, thus suggesting that MANF levels are related to metabolic homeostasis. To study the effects of dietary intervention on MANF concentrations in mice, we developed an ELISA for mouse MANF and verified its specificity using MANF knock-out (KO) tissue. A switch from high-fat to normal diet increased MANF levels and downregulated the expression of unfolded protein response (UPR) genes in the liver, indicating decreased endoplasmic reticulum (ER) stress. Liver MANF and serum adiponectin concentrations correlated inversely in mice. Our findings demonstrate that MANF expression and secretion increases with dietary intervention. The MANF correlation to adiponectin and its possible involvement in metabolic regulation and overall health warrants further studies.
Subject: ENDOPLASMIC-RETICULUM STRESS
UNFOLDED PROTEIN RESPONSE
ISCHEMIA
MANF
PROLIFERATION
ADIPONECTIN
HOMEOSTASIS
EXPRESSION
BINDING
LEPTIN
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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