Intestinal nerve cell injury occurs prior to insulin resistance in female mice ingesting a high-fat diet

Diabetic patients suffer from gastrointestinal disorders associated with dysmotility, enteric neuropathy and dysbiosis of gut microbiota; however, gender differences are not fully known. Previous studies have shown that a high-fat diet (HFD) causes type two diabetes (T2D) in male mice after 4-8 weeks but only does so in female mice after 16 weeks. This study seeks to determine whether sex influences the development of intestinal dysmotility, enteric neuropathy and dysbiosis in mice fed HFD. We fed 8-week-old C57BL6 male and female mice a standard chow diet (SCD) or a 72% kcal HFD for 8 weeks. We analyzed the associations between sex and intestinal dysmotility, neuropathy and dysbiosis using motility assays, immunohistochemistry and next-generation sequencing. HFD ingestion caused obesity, glucose intolerance and insulin resistance in male but not female mice. However, HFD ingestion slowed intestinal propulsive motility in both male and female mice. This was associated with decreased inhibitory neuromuscular transmission, loss of myenteric inhibitory motor neurons and axonal swelling and loss of cytoskeletal filaments. HFD induced dysbiosis and changed the abundance of specific bacteria, especially Allobaculum, Bifidobacterium and Lactobacillus, which correlated with dysmotility and neuropathy. Female mice had higher immunoreactivity and numbers of myenteric inhibitory motor neurons, matching larger amplitudes of inhibitory junction potentials. This study suggests that sex influences the development of HFD-induced metabolic syndrome but dysmotility, neuropathy and dysbiosis occur independent of sex and prior to T2D conditions. Gastrointestinal dysmotility, neuropathy and dysbiosis might play a crucial role in the pathophysiology of T2D in humans irrespective of sex.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:376

Enthalten in:

Cell and tissue research - 376(2019), 3 vom: 18. Juni, Seite 325-340

Sprache:

Englisch

Beteiligte Personen:

Nyavor, Yvonne [VerfasserIn]
Estill, Rachel [VerfasserIn]
Edwards, Hannah [VerfasserIn]
Ogden, Hailey [VerfasserIn]
Heideman, Kaila [VerfasserIn]
Starks, Kiefer [VerfasserIn]
Miller, Christopher [VerfasserIn]
May, George [VerfasserIn]
Flesch, Lance [VerfasserIn]
McMillan, John [VerfasserIn]
Gericke, Martin [VerfasserIn]
Forney, Larry [VerfasserIn]
Balemba, Onesmo [VerfasserIn]

Links:

Volltext

Themen:

Diabetes mellitus
Diabetic enteric neuropathy
Enteric nervous system
Gastrointestinal motility
Gut microbiota
Journal Article

Anmerkungen:

Date Completed 16.08.2019

Date Revised 01.06.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s00441-019-03002-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM294040471