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

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.

Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS)

“…This may explain the weak association of serum Lcn2 and colonic PPARγ at baseline. Contradictory results on the association of PPARγ and Lcn2 in different organs have been reported [14,22]. The reason(s) for discrepancies is unclear.…”

“…Serum LCN2 has been reported to be elevated and associated with disease activity in patients with IBD [16]. Moreover, the relationship of murine Lcn2 and peroxisome proliferator-activated receptor gamma (PPARγ) in colitis models and lipid studies reveals a relevant intracellular pathway of aberrant Lcn2 expression regulated by PPARγ [17][18][19][20][21][22]. PPARγ is a key nuclear receptor regulating both gut inflammation and mesenchymal stem cell differentiation into osteoblasts [23,24].…”

Low Circulating TRAIL Levels Are Associated with Increase of Resistin and Lipocalin-2/ngal Adipokines in Postmenopausal Women

“…Moreover, it has been suggested that PPAR γ might play a key role in the physiological processes involving both resistin and lipocalin-2/ngal. On the one hand, lipocalin was found to be a selective modulator of PPAR γ activation [ 26 ], and on the other hand, the activation of this factor with a pharmacological agonist (e.g., thiazolidinediones) was found to affect the expression of several adipokines, including resistin [ 27 ]. Of interest, Zoller and colleagues have recently addressed the role of TRAIL in adipogenesis, showing that human recombinant TRAIL was able to interfere with adipogenesis differentiation by downregulating several key adipogenic transcription factors, including PPAR γ , C/EBP α , and C/EBP δ , highlighting an unknown function of TRAIL in the regulation of adipose tissue homeostasis [ 28 ].…”

Lipocalin-2 abrogates epithelial cell cycle arrest by PPARγ inhibition

“…Other authors demonstrated that Lcn-2 significantly promotes human pulmonary artery smooth muscle cell These authors contributed equally: Georgina Hotter, Anna Sola. proliferation by activating the PI3K/Akt-pathway [11]. Furthermore, Lcn-2 is a modulator of peroxisome proliferator-activated receptor (PPAR)-γ activation and has a proven role in lipid homoeostasis and energy expenditure [12,13]. PPAR-γ activation downregulates cell proliferation by inhibiting Akt phosphorylation and its downstream targets [14].…”