Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme

Mett, Janine; Lauer, Anna A.; Janitschke, Daniel; Griebsch, Lea V.; Theiss, Elena L.; Grimm, Heike S.; Koivisto, Hennariikka; Tanila, Heikki; Hartmann, Tobias; Grimm, Marcus O. W.

doi:10.3390/cells10112941

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Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme

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Marcus O. W. Grimm

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Biosciences Zoology/Physiology-Neurobiology, Faculty NT-Natural Science and Technology, Saarland University, 66123 Saarbrücken, Germany

Experimental Neurology, Saarland University, 66424 Homburg, Germany

A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland

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Deutsches Institut für Demenzprävention, Saarland University, 66424 Homburg, Germany

⁵

Nutrition Therapy and Counseling, Campus Rheinland, SRH University of Applied Health Sciences, 51377 Leverkusen, Germany

Author to whom correspondence should be addressed.

Academic Editor: Irene Cozar-Castellano

Cells 2021, 10(11), 2941; https://doi.org/10.3390/cells10112941

Received: 24 June 2021 / Revised: 14 October 2021 / Accepted: 26 October 2021 / Published: 29 October 2021

(This article belongs to the Special Issue Insulin-Degrading Enzyme in Health and Disease)

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Abstract

The accumulation of amyloid β-protein (Aβ) is one of the major pathological hallmarks of Alzheimer’s disease. Insulin-degrading enzyme (IDE), a zinc-metalloprotease, is a key enzyme involved in Aβ degradation, which, in addition to Aβ production, is critical for Aβ homeostasis. Here, we demonstrate that saturated medium-chain fatty acids (MCFAs) increase total Aβ degradation whereas longer saturated fatty acids result in an inhibition of its degradation, an effect which could not be detected in IDE knock-down cells. Further analysis of the underlying molecular mechanism revealed that MCFAs result in an increased exosomal IDE secretion, leading to an elevated extracellular and a decreased intracellular IDE level whereas gene expression of IDE was unaffected in dependence of the chain length. Additionally, MCFAs directly elevated the enzyme activity of recombinant IDE, while longer-chain length fatty acids resulted in an inhibited IDE activity. The effect of MCFAs on IDE activity could be confirmed in mice fed with a MCFA-enriched diet, revealing an increased IDE activity in serum. Our data underline that not only polyunsaturated fatty acids such as docosahexaenoic acid (DHA), but also short-chain fatty acids, highly enriched, for example in coconut oil, might be beneficial in preventing or treating Alzheimer’s disease. View Full-Text

Keywords: Aβ degradation; insulin-degrading enzyme; Alzheimer´s disease; fatty acids; medium-chain fatty acids; lauric acid; myristic acid; coconut oil

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MDPI and ACS Style

Mett, J.; Lauer, A.A.; Janitschke, D.; Griebsch, L.V.; Theiss, E.L.; Grimm, H.S.; Koivisto, H.; Tanila, H.; Hartmann, T.; Grimm, M.O.W. Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme. Cells 2021, 10, 2941. https://doi.org/10.3390/cells10112941

AMA Style

Mett J, Lauer AA, Janitschke D, Griebsch LV, Theiss EL, Grimm HS, Koivisto H, Tanila H, Hartmann T, Grimm MOW. Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme. Cells. 2021; 10(11):2941. https://doi.org/10.3390/cells10112941

Chicago/Turabian Style

Mett, Janine, Anna A. Lauer, Daniel Janitschke, Lea V. Griebsch, Elena L. Theiss, Heike S. Grimm, Hennariikka Koivisto, Heikki Tanila, Tobias Hartmann, and Marcus O. W. Grimm. 2021. "Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme" Cells 10, no. 11: 2941. https://doi.org/10.3390/cells10112941

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Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme

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