Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity.
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.
['Tsai|Sheng-Feng|SF|', 'Wu|Hung-Tsung|HT|', 'Chen|Pei-Chun|PC|', 'Chen|Yun-Wen|YW|', 'Yu|Megan|M|', 'Tzeng|Shun-Fen|SF|', 'Wu|Pei-Hsuan|PH|', 'Chen|Po-See|PS|', 'Kuo|Yu-Min|YM|']
D000679:Amygdala D000818:Animals D003924:Diabetes Mellitus, Type 2 D059305:Diet, High-Fat D007333:Insulin Resistance D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009473:Neuronal Plasticity D013315:Stress, Psychological
Diabetes Social defeat Amygdalar lesion Glucose homeostasis