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Published on: November 27, 2019
Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Upregulated with Therapeutic Fasting in Humans and Diet Fat
Emilia Galli1, Jari Rossi2, Thomas Neumann3,4
1Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
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.
Insights
Therapeutic fasting and dietary changes increase levels of Mesencephalic astrocyte-derived neurotrophic factor (MANF). MANF may play a role in metabolic regulation and overall health, warranting further investigation.
Area of Science:
- Metabolic regulation
- Neurotrophic factors
- Cellular stress
Background:
- Dietary restriction offers metabolic benefits and combats age-related decline.
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) has demonstrated protective cellular effects in various disease models.
- The relationship between MANF and fasting-induced metabolic improvements remains largely unexplored.
Purpose of the Study:
- To investigate the association between circulating MANF concentrations and the positive effects of fasting.
- To examine the impact of dietary interventions on MANF levels and endoplasmic reticulum (ER) stress markers in both humans and mice.
Main Methods:
- Quantified plasma MANF levels in 40 human subjects before and after a 15-day therapeutic fast using ELISA.
- Developed and validated a mouse MANF ELISA assay.
- Analyzed changes in liver MANF, serum adiponectin, and unfolded protein response (UPR) gene expression in mice switched from a high-fat to a normal diet.
Main Results:
- Plasma MANF concentrations significantly increased after therapeutic fasting in humans.
- MANF levels in mice increased following a switch to a normal diet, accompanied by reduced ER stress markers (UPR genes).
- Inverse correlations were observed between MANF and adiponectin levels in both human plasma and mouse serum/liver.
Conclusions:
- Dietary interventions, including fasting and diet switching, enhance MANF expression and secretion.
- MANF's inverse correlation with adiponectin suggests a role in metabolic homeostasis.
- Further research is warranted to elucidate MANF's function in metabolic regulation and its contribution to overall health.
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