Inflammation and autophagy in peripheral nerves of rodent models with metabolic syndrome and type 2 diabetes mellitus

Petra Baum; Thomas Ebert; Nora Klöting; Sontje Krupka; Matthias König; Sabine Paeschke; Peggy Stock; Michal Bulc; Matthias Blüher; Katarzyna Palus; Marcin Nowicki; Joanna Kosacka

doi:10.1016/j.neures.2025.04.002

Inflammation and autophagy in peripheral nerves of rodent models with metabolic syndrome and type 2 diabetes mellitus

Neurosci Res. 2025 Jul:216:104899. doi: 10.1016/j.neures.2025.04.002. Epub 2025 Apr 17.

Authors

Affiliations

¹ Department of Neurology, University of Leipzig, Liebigstr. 20, Leipzig 04103, Germany.
² University of Leipzig Medical Center, Medical Department III - Endocrinology, Nephrology, Rheumatology, Liebigstr. 20, Leipzig 04103, Germany.
³ Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Ph.-Rosenthal-Str. 27, Leipzig 04103, Germany.
⁴ Institute for Biology, Institute for Theoretical Biology, Humboldt-University Berlin, Philippstraße 13, Berlin 10115, Germany.
⁵ Institute of Anatomy, University of Leipzig, Liebigstr. 13, Leipzig 04103, Germany.
⁶ Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena 07747, Germany.
⁷ Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Street Oczapowskiego 14, Olsztyn 10-719, Poland.
⁸ University of Leipzig Medical Center, Medical Department III - Endocrinology, Nephrology, Rheumatology, Liebigstr. 20, Leipzig 04103, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Ph.-Rosenthal-Str. 27, Leipzig 04103, Germany.
⁹ Department of Neurology, University of Leipzig, Liebigstr. 20, Leipzig 04103, Germany; Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena 07747, Germany. Electronic address: Joanna.Kosacka@medizin.uni-leipzig.de.

PMID: 40252698
DOI: 10.1016/j.neures.2025.04.002

Abstract

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2D) are associated with inflammation and the accumulation of macrophages in peripheral nerves, which increases the risk of developing peripheral neuropathy (PN). We have previously investigated that macrophage infiltration in the peripheral nerves of animals with T2D (leptin-deficient ob/ob mice, leptin receptor-deficient db/db) correlated with PN, whereas this process in animals with MetS (Wistar Ottawa Karlsburg W (RT1u) WOKW rat) did not lead to neuropathic changes. Additional data presented in this study suggest an association between increased mRNA expression of the anti-inflammatory marker IL-10 and autophagy in the prevention of neuropathy.

Keywords: Autophagy; Inflammation; Metabolic syndrome; PDN; T2D; WOKW rat; db/db mice; ob/ob mice.

MeSH terms

Animals
Autophagy* / physiology
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / metabolism
Diabetes Mellitus, Type 2* / pathology
Diabetic Neuropathies / metabolism
Diabetic Neuropathies / pathology
Disease Models, Animal
Inflammation* / metabolism
Inflammation* / pathology
Macrophages / metabolism
Male
Metabolic Syndrome* / complications
Metabolic Syndrome* / metabolism
Metabolic Syndrome* / pathology
Mice
Peripheral Nerves* / metabolism
Peripheral Nerves* / pathology
Rats
Rats, Wistar
Receptors, Leptin

Substances

Receptors, Leptin