The endocrine function of adipose tissue and its importance for initiation and development of insulin resistance and diabetes

Endocrine production of adipose tissue is a very complex process affected by numerous endogenous and exogenous stimuli. Peroxisome proliferator-activated receptors-alpha (PPAR-) are important modulators of metabolic processes which can also affect endocrine function of adipose tissue. Recently, numerous novel factors produced by adipose tissue with important metabolic effects were identified. Some of them can directly bind PPAR receptors. One of the examples of these factors is fatty acid binding protein 4 (FABP4) which can directly bind PPAR receptors and indirectly modify its activation by changing availability of endogenous PPAR ligands -free fatty acids. We hypothesized that the mechanism of action of PPAR receptors to metabolic processes may partially lie in their complex interaction with adipose tissue-derived hormones. The unraveling of these interactions may have important consequences in finding approaches to treat patients with type 2 diabetes mellitus. (...) In summary, our data show an important role for the interplay of PPAR activation and endocrine function of adipose tissue in metabolic regulations which may have important clinical consequences

The fold change (FC) induced by different TLR agonists, calculated from the area under the curve for the <i>IL6</i> gene expression in a time course over 8 hours in healthy and polyp derived airway epithelium.

<p>The value represents an average cumulative gene expression response to the TLR agonists in epithelial cells isolated from 6 healthy controls and 5 polyps with a standard deviation. Statistical significance comparing the differences in cumulative gene expression levels between normal or polyp epithelium is indicated as <i>p</i> value.</p

The fold change (FC) induced by different TLR agonists, calculated from the area under the curve for <i>IL33</i>) in a time course over 8 hours in healthy and polyp derived airway epithelium.

<p>The value represents an average cumulative gene expression to the TLR agonists in epithelial cells isolated from 6 healthy controls and 5 polyps with a standard deviation. Statistical significance comparing the differences in cumulative gene expression levels between normal or polyp epithelium is indicated as <i>p</i> value.</p

Baseline levels expression comparison of ATF-3, EGR-1, DUSP-1, and NFKB1 in healthy or polyp epithelium.

<p>Expression profiles were corrected for the expression of the housekeeping gene. The experiment was performed in a biological triplicate. Statistical significant differences in baseline expression between healthy and polyposis epithelium is indicated (*) if <i>p</i> < 0.05.</p

The fold change (FC) induced by different TLR agonists, calculated from the area under the curve for <i>TSLP</i> in a time course over 8 hours in healthy and polyp derived airway epithelium.

<p>The value represents an average cumulative gene expression to the TLR agonists in epithelial cells isolated from 6 healthy controls and 5 polyps with a standard deviation. Statistical significance comparing the differences in cumulative gene expression levels between normal or polyp epithelium is indicated as <i>p</i> value.</p

Mediators secreted 8h or 24h after poly(I:C) stimulation alone or additionally pre-exposed for 24 hours to HDM.

<p>Cell-free supernatants were analyzed for the presence of cytokines and chemokines in relation to stimulation by poly(I:C) with or without HDM pre-exposure. The table shows cytokines that are: HDM-enhanced in response to poly(I:C); HDM-down-regulated in response to poly(I:C) and not affected by HDM pre-exposure. The concentration values are given in pg/mL and standard deviations are in brackets and represent an average of a triplicate experiment. Fold changes (FC) were calculated as a ratio between HDM pre-stimulation followed by poly(I:C) exposure condition to HBSS pre-exposure followed by poly(I:C) stimulation condition. Fold changes and values were considered significant if p<0.05. Statistically significant induction of cytokines production by poly(I:C) compared to non-induced control conditions is marked with (^#) and significant effect of HDM pre-exposure to the FC values are marked with (*). B.d – below the detection limit.</p

Network interaction model of the genes that make up the core response of airway epithelial cells upon HDM allergen exposure.

<p>The principal cellular locations of the gene products (extra cellular region, membrane, cytoplasm, and nucleus) are indicated and their transcriptional interaction.</p

Mediators secreted 8 or 24(I:C) or HDM.

<p>Cell-free supernatants were analyzed for the presence of cytokines and chemokines. The first part of the table shows mediators induced by 8 or 24 hours stimulation with both HDM and poly(I:C). In the second part, mediators induced only by poly(I:C) was collected. The bottom of the table shows a cytokine which was not affected by either of the stimuli. The concentration values are given in pg/mL and standard deviations are in brackets and represent the average of three biological replicates. Fold changes (FC) were calculated as a ratio between stimulated and control cells and if significant (p<0.05), marked with (^#). Significant differences (p<0.05) between levels of induction by HDM and poly(I:C) are marked with (*). B.d – below the detection limit.</p

Detailed expression analysis of selected genes in response to poly(I:C) challenge.

<p>The NCI-H292 cell line was stimulated with poly(I:C) in a time course over 24 hours and expression profiles of: <i>ATF3</i>, <i>EGR1</i>, <i>DUSP1</i>, <i>FOS</i>, <i>FOSL1</i>, <i>MYC</i>, <i>JUN</i>, <i>IL6</i>, <i>NKB1,</i> and <i>NFKB2</i> were investigated. Graphs show genes that are: A) induced rapidly after stimulation with poly(I:C); B) induced 2 hours after poly(I:C); C) late-induced; D) not affected by poly(I:C) stimulation. Each time point represents an average of three biological replicates ± standard deviation.</p