Format

Send to

Choose Destination
Neuroendocrinology. 2018;107(2):147-157. doi: 10.1159/000491018. Epub 2018 Jun 19.

Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity.

Author information

1
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
2
Department of Family Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
3
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
4
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
5
Department of Chemistry, University of Virginia, Charlottesville, Virginia, USA.
6
Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
7
Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
8
Addiction Research Center, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
9
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

BACKGROUND:

The notion that exposure to chronic stress predisposes individuals to developing type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known about whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D.

METHODS:

We used an 11-week high-fat diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementation of a 10-day social defeat (SD) stress protocol.

RESULTS:

Mice receiving SD at the beginning of the HFD feeding aggravated HFD-induced insulin resistance and white adipose tissue expansion. HFD mice had higher levels of plasma corticosterone, which was not affected by the SD. The SD stress upregulated the expression of TrkB and synaptotagmin-4 in the amygdala of HFD mice. Bilateral lesions of the central amygdalae before SD stress inhibited the stress-induced aggravating effect without affecting the HFD-induced elevation of plasma corticosterone.

CONCLUSIONS:

Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D.

KEYWORDS:

Amygdalar lesion; Diabetes; Glucose homeostasis; Social defeat

PMID:
29920496
DOI:
10.1159/000491018
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center