Glucose intolerance after chronic stress is related with downregulated PPAR-γ in adipose tissue

Vitor H Pereira,Vânia Lages,Joana Almeida-Palha,Fernanda Marques,Osborne F X Almeida,Alexandre Patchev,João J Cerqueira,Nuno Sousa,Filipa G Pereira

doi:10.1186/s12933-016-0433-2

Vitor H Pereira, Vânia Lages + Show 7 more

Open Access

https://doi.org/10.1186/s12933-016-0433-2

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Abstract

BackgroundChronic stress is associated with increased risk of glucose intolerance and cardiovascular diseases, albeit through undefined mechanisms. With the aim of gaining insights into the latter, this study examined the metabolic profile of young adult male rats that were exposed to chronic unpredictable stress.MethodsYoung adult male rats were submitted to 4 weeks of chronic unpredictable stress and allowed to recover for 5 weeks. An extensive analysis including of morphologic, biochemical and molecular parameters was carried out both after chronic unpredictable stress and after recovery from stress.ResultsAfter 28 days of chronic unpredictable stress (CUS) the animals submitted to this protocol displayed less weight gain than control animals. After 5 weeks of recovery the weight gain rebounded to similar values of controls. In addition, following CUS, fasting insulin levels were increased and were accompanied by signs of impaired glucose tolerance and elevated serum corticosteroid levels. This biochemical profile persisted into the post-stress recovery period, despite the restoration of baseline corticosteroid levels. The mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-γ and lipocalin-2 in white adipose tissue were, respectively, down- and up-regulated.ConclusionsReduction of PPAR-γ expression and generation of a pro-inflammatory environment by increased lipocalin-2 expression in white adipose tissue may contribute to stress-induced glucose intolerance.

Highlights

Chronic stress is associated with increased risk of glucose intolerance and cardiovascular diseases, albeit through undefined mechanisms
Adipose tissue inflammation is characterized by macrophage infiltration and expression of proinflammatory mediators such as lipocalin-2 (Lcn2) [13], Pereira et al Cardiovasc Diabetol (2016) 15:114 tumor necrosis factor-α (TNF-α), interleukin (Il)-1, Il-6, and chemoattractant molecules, such as monocyte chemoattractant protein-1 (Mcp-1) [14])
This study aims to unveil biological markers that establish the molecular basis of stress-induced glucose intolerance, with a special emphasis on the visceral white adipose tissue

Summary

Introduction

Chronic stress is associated with increased risk of glucose intolerance and cardiovascular diseases, albeit through undefined mechanisms. Epidemiological studies show that chronic stress increases the risk of diabetes and metabolic syndrome [2]. Increases in corticosteroid secretion have long been considered to have a causal role in glucose intolerance associated with stress [3, 4]. These hormones enhance hepatic gluconeogenesis, inhibit the secretion and action of insulin, promote differentiation and proliferation of adipocytes, redistribution of fat, and decrease lipoprotein–lipase activity [5, 6]. Adipose tissue inflammation is characterized by macrophage infiltration and expression of proinflammatory mediators such as lipocalin-2 (Lcn2) [13], Pereira et al Cardiovasc Diabetol (2016) 15:114 tumor necrosis factor-α (TNF-α), interleukin (Il)-1, Il-6, and chemoattractant molecules, such as monocyte chemoattractant protein-1 (Mcp-1) [14])

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