**5. Adiponectin and dyslipidemia: Relationship of adiponectin, fibroblast growth factor 21 and adipocyte fatty acid binding protein levels to dyslipidemic phenotypes – Pilot study**

### **5.1. Background**

Adipose tissue is an important place of many metabolic and inflammatory processes. Adipokines are considered to be the mediators of these pathways.

Adiponectin (ADP, AdipoQ, apM1, GBP28) is a "favourable" adipokine of fat tissue circulating at relatively high concentrations in human plasma. Adiponectin has the protective effects in early stages and during progression of atherosclerosis probably by its antiinflammatory and antiatherogenic actions.

Fibroblast growth factor 21 (FGF 21) is also a "favourable" cytokine of adipose tissue considered as a new metabolic regulator of non insulin dependent glucose transport in cells [37]. Systematic administration of FGF 21 decreases plasma levels both of glucose and triglycerides, and leads to improving of lipoprotein profiles in genetic compromised FGF transgenic mice and primates [38]. Increased levels of FGF 21 and a negative correlation with HDL and adiponectin were found in patients with metabolic syndrome [39].

Adipocyte fatty acid binding protein (A-FABP) is a "unfavourable" adipokine, probably a new marker and/or predictor of metabolic syndrome [40]. A-FABP is a dominant cytoplasmic protein of mature adipocytes and a regulator of lipid and glucose metabolism, present also in macrophages of fat tissue. Its expression is induced by oxidated LDL [41]. Higher levels of A-FABP are associated with increased fasting glucose, triglycerides, insulin BMI and waist circumference, and decreased HDL in patients with metabolic syndrome. Inhibition of A-FABP action is associated with reversion of atherosclerosis (improving of diabetic and lipoprotein parameters).

The aim of our study was to evaluate the relationship between adiponectin, FGF 21 and A-FABP levels and dyslipidemic phenotypes defined on the basis of concentrations of triglycerides and apolipoprotein B [25].

#### **5.2. Subjects, material and methods**

119 pacients of Lipid Center at Faculty Hospital Olomouc were included on the pilot scheme. Routine serum biochemical parameters were analyzed on Modular SWA (Roche, Switzerland) in the day of blood collection. Levels of ADP, FGF 21 and A-FABP were determinated by imunochemical Elisa methods (BioVendor, Czech Republic). The analytical characteristics from data sheets were verificated according to laboratory protocol for all procedures.

119 individuals were divided into four dyslipidemic phenotypes (DLP) according to Sniderman classification- see Table 6.


**Table 6.** Classification of dyslipidemic phenotypes

#### **5.3. Results**

692 Lipoproteins – Role in Health and Diseases

atherosclerosis.

**5.1. Background** 

adiponectin levels were found in patients with CAD independently of other risk factors. Therefore, the finding of positive and independent association of adiponectin with the marker of endothelial dysfunction VCAM 1 was suprising. This positive association was present both in patients with CVD and dyslipidemic subjects without CVD, but it was not significant in healthy subjects without dyslipidemia. We hypothesize that adiponectin, which accumulates in the arterial wall only in place of endothelial injury and atherosclerotic plaques (that is the same places where VCAM 1 is expressed) may be involved in shedding of ectodomains of VCAM 1 from endothelial surface. This may represent a mechanism by which VCAM 1 effects on the cell surface can be downregulated. In this way, adiponectin could protect vascular wall from adhesion of leukocytes and thus from progression of

**5. Adiponectin and dyslipidemia: Relationship of adiponectin, fibroblast** 

Adipose tissue is an important place of many metabolic and inflammatory processes.

Adiponectin (ADP, AdipoQ, apM1, GBP28) is a "favourable" adipokine of fat tissue circulating at relatively high concentrations in human plasma. Adiponectin has the protective effects in early stages and during progression of atherosclerosis probably by its

Fibroblast growth factor 21 (FGF 21) is also a "favourable" cytokine of adipose tissue considered as a new metabolic regulator of non insulin dependent glucose transport in cells [37]. Systematic administration of FGF 21 decreases plasma levels both of glucose and triglycerides, and leads to improving of lipoprotein profiles in genetic compromised FGF transgenic mice and primates [38]. Increased levels of FGF 21 and a negative correlation

Adipocyte fatty acid binding protein (A-FABP) is a "unfavourable" adipokine, probably a new marker and/or predictor of metabolic syndrome [40]. A-FABP is a dominant cytoplasmic protein of mature adipocytes and a regulator of lipid and glucose metabolism, present also in macrophages of fat tissue. Its expression is induced by oxidated LDL [41]. Higher levels of A-FABP are associated with increased fasting glucose, triglycerides, insulin BMI and waist circumference, and decreased HDL in patients with metabolic syndrome. Inhibition of A-FABP action is associated with reversion of atherosclerosis (improving of

The aim of our study was to evaluate the relationship between adiponectin, FGF 21 and A-FABP levels and dyslipidemic phenotypes defined on the basis of concentrations of

with HDL and adiponectin were found in patients with metabolic syndrome [39].

**growth factor 21 and adipocyte fatty acid binding protein levels to** 

**dyslipidemic phenotypes – Pilot study** 

antiinflammatory and antiatherogenic actions.

diabetic and lipoprotein parameters).

triglycerides and apolipoprotein B [25].

Adipokines are considered to be the mediators of these pathways.

Basic clinical characteristics are shown in Table 7. Concentrations of adipokines and other biochemical parameters are given in Table 8.


**Table 7.** Basic clinical characteristics of DLP groups


Differences between groups were analyzed with ANOVA. Parameters with skewed distribution (TGL, ADP, FGF 21, A-FABP) were log transformed to normalize their distributions before statistical analyses.

\* DLP2 vs. DLP1 and DLP3, p < 0.01, \*\* DLP4 vs. DLP1 and DLP3, p < 0.01, \*\*\* DLP4 vs. DLP1 and DLP3, p < 0.05

**Table 8.** Adipokines and other biochemical parameters in connection with DLP

The highest levels of ADP were observed in DLP1 (no significance). Suprisingly, there was seen no negative association between adiponectin levels and DLP2 (DLP4). FGF 21 and A-FABP were significantly increased in the groups with the most important atherogenic potential (DLP2, DLP4). These two parameters correlated with higher levels of triglycerides, fasting glucose, BMI and lower HDL cholesterol, both in DLP2 and DLP4.
