Hyperglycemia-induced changes in miRNA expression patterns in epicardial adipose tissue of piglets.

MicroRNAs (miRNAs) are a class of molecular posttranscriptional regulators found to participate in numerous biological mechanisms, such as adipogenesis, fat deposition, or glucose metabolism. Additionally, a detailed analysis on the molecular and cellular mechanisms of miRNA-related effects on metabolism leads to developing novel diagnostic markers and therapeutic approaches. To identify miRNA whose activity changed in epicardial adipose tissue in piglets during hyperglycemia, we analyzed the different miRNA expression patterns between control and hyperglycemia groups. The microarray analysis selected three differentially expressed microRNAs as potential biomarkers: hsa-miR-675-5p, ssc-miR-193a-3p, and hsa-miR-144-3p. The validation of miRNA expression with real-time PCR indicated an increased expression levels of ssc-miR-193a-3p and miR-675-5p, whereas the expression level of hsa-miR-144-3p was lower in epicardial adipose tissue in response to hyperglycemia (P<0.01). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that these miRNAs differentially expressed between hyperglycemic and control piglets are involved in insulin, adipocytokine, and phosphatidylinositol 3-kinase-Akt signaling pathways, and development of type 2 diabetes as well. The results suggested that hyperglycemia can significantly affect the expression patterns of miRNA in porcine adipose tissue.

Adipose Tissue Tumor Necrosis Factor-α. and Interleukin-6 Response to Glucocorticoid Treatment during Inflammation.

The study was performed to examine the actions of glucocorticoids on cytokine (TNF-α and IL-6) concentrations in blood plasma, adipose tissue and cytokines gene expression during acute (streptozotocin, STZ treatment) and chronic inflammation (overweight) in Swiss mice. The experiment was carried out on 6-week-old animals divided into two groups: I - non-obese (fed with a commercial food) and II - overweight mice (fed with a high-fat diet). In each group mice were divided into 4 experimental subgroups: I - control, II - acute inflammation (STZ), III - treated with glucocorticoids (DEX), and IV - STZ with DEX. After injections the animals were decapitated, blood and white adipose tissue (WAT) was quickly removed and directed to measure the plasma levels, tissue concentrations and gene expression of the cytokines (TNF-α, IL-6). Three weeks of treatment with a high-fat diet resulted in increased body weight gain and plasma level of cytokines, whereas did not change TNF-c and IL-6 mRNA gene expression in control animals. STZ, administered once, changed the TNF-α & and IL-6 concentrations in a different manner according to the diet. The TNF-a and IL-6 actions in mice white adipose tissue are down-regulated after glucocorticoids treatment only in overweight animals. The obtained results suggest that glucocorticoids' effects on adipose tissue immune response, both in a pro- and an anti-inflammatory manner, depend on the nutritional status.

The Effect of CRH, Dexamethasone and Naltrexone on the Mu, Delta and Kappa Opioid Receptor Agonist Binding in Lamb Hypothalamic-Pituitary-Adrenal Axis.

The aim of the study was to evaluate changes in the opioid receptor binding (mu, delta and kappa) in the hypothalamus, anterior pituitary and adrenal cortex (HPA) of lambs treated in vivo with corticotrophin releasing hormone (CRH), naltrexone, an opioid receptor antagonist (NAL), and dexamethasone, a potent cortisol analog (DEX). Experiment was carried out on 3 months old female lambs of polish mountain strain. Lambs received a single i.v. injection of NaCl (control), CRH (alone or in combination with naltrexone), naltrexone or dexamethasone. One hour later animals were decapitated under anaesthesia, tissues were dissected out and receptor binding assays were performed with radioligands for each type of opioid receptors--3H-DAGO, 3H-DPDPE and 3H-EKC for mu, delta and kappa receptor, respectively. Coexistence of specific binding sites for each type of opioid receptor was demonstrated in all levels of HPA axis of control lambs, however their distribution was uneven. Acute treatment with CRH, DEX and NAL caused downregulation or upregulation of mu, delta, kappa receptor binding in each level of HPA axis. CRH effects on mu, delta and kappa opioid receptor binding varied within the HPA axis and were modulated by naltrexone. Treatment with naltrexone increased in vitro mu, delta and kappa receptor binding in most tested structures except delta receptor binding in adrenal (decrease by 52%) and kappa receptor binding in pituitary (decrease by 41%). Dexamethasone significantly decreased the mu, delta and kappa opioid receptor binding in adrenal cortex but differentially affected opioid receptor binding in hypothalamus and pituitary. It seems probable that endogenous opioid peptides acting through mu, delta and kappa receptors interact with the hormones released from the hypothalamic-pituitary-adrenal axis in physiological and pathophysiological situations.

mTOR Pathway - Novel Modulator of Astrocyte Activity.

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that belongs to the phosphoinositide-3-kinase-related family and has a crucial role in the integration of growth factors, energy factors and nutrient signaling. Abnormal activity of mTOR kinase can cause many neuropathologies, including brain tumours and neurodegenerative diseases. The study confirms that the use of a kinase inhibitor - rapamycin, allows to limit proliferation including inhibition of tumor cells and immune responses. The review presents current knowledge about the role of mTOR in the modulation of nervous system activity focusing on astrocytes which are involved in the maintenance of nervous system homeostasis and support neuronal function. Astroglial activity is associated with the pathogenesis of neurodegenerative diseases like Alzheimer's disease (AD) or Parkinson's disease (PD). Effect of mTOR and its inhibitor on central nervous system functions, in particular astrocytes, is still not fully undersood.