Aim. Aim of this study was to evaluate the possible alterations of the

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Title: Cardio-metabolic and inflammatory biomarkers in a animal model of obesity

Introduction. Cancer, cardiovascular diseases and diabetes, which are

the main causes of morbility and mortality in the western world, present similar risk factors, first of all obesity and diabetes. To date, the mechanisms which associate biochemical disorders of the metabolic syndrome to the development of chronic diseases are not fully understood, however the endocrine function of adipose tissue appears to have a central role. The fat produces a plenty of biological substances, the adipocytokines, which, regulating local and systemic inflammation, affect organ metabolism and DNA integrity.

Aim. Aim of this study was to evaluate the possible alterations of the

system of adiponectin (ADN), an insulin-sensitizing and anti-

inflammatory adipokine, in tissues known to be the target of chronic

diseases associated to obesity and diabetes. For this, mRNA

expression of ADN, of its specific receptors (AdipoR1, AdipoR2,

T-cadherin) as well as of its principal intracellular signaling

(AMPK1/2 e PPAR) were determined. The mRNA expression of

inflammatory cytokines, such as TNF- and IL-6, was also evaluates.




Materials and Methods. The study included 40 male Zucker rats

subdivided in four groups (n = 10 each): 1. Zucker fatty rats (O); 2.

control Zucker rats (CO); 3. Zucker diabetic fatty rats (ZDF-D);

4. control Zucker rats (ZDF-CD). The rats were studied both in fasting and in hyperglycemic conditions. Total RNA was extracted from tissue samples obtained from heart, liver and visceral adipose fat;

RNA concentration, purity and integrity were determined. The mRNA expressions of the studied genes were evaluated by Real-Time PCR, after setting the optimal reaction conditions. Ten candidate reference genes were checked for each tissue and the three more stable selected for the normalization of real-time PCR data.

Results. The most stably expressed genes were: SDHA, HPRT-1 and

TBP in cardiac tissue; SDHA, GUSB and ACTB in liver tissue; TBP,

TFRC and HPRT-1 in visceral adipose tissue. No modification of

ADN mRNA levels was found in the tissues of both obese and

diabetic rats. Significant variations were observed for specific

receptors: AdipoR1 mRNA level resulted decreased in cardiac tissue

of diabetic rats (p = 0.0016); AdipoR2 increased in obese rats in the

liver (p = 0.0007) and in the adipose tissue (p = 0.017) while it

decreased in diabetic rats in the liver (p = 0.017) and in the heart

(p = 0.023). T-cadherin mRNA levels resulted significantly increased

in all the tissues analyzed of obese rats: in the cardiac tissue

(p = 0.015), in the liver (p < 0.0001), and in the visceral adipose tissue

(p = 0.0014). As regard to signaling pathways, no important

modification was found for AMPK-1/2 and PPAR while




AMPK-2 decreased in the cardiac tissue in obese rats (p = 0.037) and in the liver (p = 0.048) of diabetic rats. Hyperglycemia or fasting condition did not changed the mRNA expression for all the analyzed genes. Inflammatory cytokine expression resulted increased in the visceral adipose tissue of obese rats (TNF-, p = 0.041; IL-6,

p = 0.017).

Conclusions. The results of this work indicate that the ADN system is

modulated by obesity and diabetes mainly at the level of specific

receptors. This suggests that, in a condition of metabolic alteration,

the ADN uptake is of pivotal importance. This closely agrees with the

up-regulation of T-cadherin, an ADN co-receptor that promote ADN

uptake in tissues, found in all the analyzed tissues of obese rats. This

observation suggests a possible compensatory effect devoted to

increase the ADN beneficial effects in this metabolic condition.




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