Aerobic exercise improves microvascular dysfunction in fructose fed hamsters
Introduction
Humans tend to choose a more palatable diet and sugars such as fructose and glucose operate as ordinary sweeteners. Given the substantial participation of fructose in Western diet, it appears important to elucidate its metabolic effects and potential cardiovascular risk. For this purpose, the microcirculation could be a primary evaluation spot in individual's health, even in the absence of ill symptoms. The endothelium is essential to autoregulatory mechanisms and nitric oxide (NO) production plays an important role on vascular tone and health (Moncada and Higgs, 1993). Adequate microvascular flow should match organ function and its impairment is associated to organ failure in critically ill patients (Sakr et al., 2004). Endothelial dysfunction (ED) is characterized by reduction in the bioavailability of vasodilators, mainly NO, and activation of endothelial cells elicited by a predominant pro-inflammatory, proliferative and pro-coagulant milieu state (Anderson, 1999). Therewith, altered blood flow and inflammation incite changes on vascular hemodynamic, which in terms of macromolecular permeability is reflected on altered solute diffusion and raise in exchange membrane area. Vascular and microvascular permeability make it possible to correlate extravasation spots to microvascular morphology in several preparations, like for instance the hamster cheek pouch.
The cheek pouch, an invagination of the oral mucosa that extends under the subcutaneous tissue down to the shoulder region, is an appropriate preparation to study microcirculatory function/dysfunction. Its blood supply comes mainly from the carotid arteries and it remains stable for 5 to 6 h (Duling, 1973). There are several advantages to the use of this preparation (1) ease access, (2) highly vascularized with all classes of microcirculatory vessels, (3) clarity and (4) the possibility to observe either skeletal muscle or subcutaneous microcirculatory beds.
Studies concerning fructose intake have been reported to induce insulin resistance, hyperglycemia, hypertriglyceridemia in rats (Tobey et al., 1982, Zavaroni et al., 1980), to reduce glucose uptake by adipocytes in vitro and endothelium-dependent vasodilation elicited by acetylcholine in aortic strips (Kotchen et al., 1997), to reduce tyrosine phosphorilation of IRS-1 in the soleus muscle (Hyakukoku et al., 2003), to significantly increase fasting plasma insulin without hyperglycemia, to decrease muscarinic receptors and to increase the dependence on nitric oxide and to impair α2-adrenergic-mediated relaxation (Takagawa et al., 2001). However few novel data have shown its effects on microvascular permeability. Taking these data into account, strategies that set microcirculation as therapeutic target could be of great importance.
Physical activity has gained visibility as non-pharmacological treatment to obesity and its co-morbidities. The skeletal muscle constitutes approximately 40% of total body weight and is considered the most important determinant of peripheral vascular sensibility to insulin (Smith and Muscat, 2005) and the place for capitation, storage and liberation of glucose (Nuutila et al., 1992). Regular exercise practice is associated to reduction in primary (Myers et al., 2002) and secondary (Piepoli et al., 2010) vascular events, reduction of adiposity, and improvement of several metabolic risk factors including triglycerides (TG), high density lipoprotein-C (HDL-C), insulin and HOMA-IR when both regimens result in similar energy expenditure (Cho et al., 2011). Physical exercise benefits are not necessarily related to adiposity loss but also to improvement on vascular hemodynamic, and as a consequence, an improvement of type 2 diabetes and obesity related cardiovascular risks even without weight loss.
Therefore, our objectives in the present investigation were to evaluate microcirculatory effects, using the hamster cheek pouch preparation, of the substitution of the drinking water by 10% fructose solution during 20 weeks and the possibility of reversing these effects with a light/moderate aerobic exercise training program (AET) applied during the last 4 weeks of carbohydrate overload. Our hypothesis consisted on determining the capacity of reversion of the microvascular damage elicited by carbohydrate overload using a non-pharmacological way of treatment which, in this case, was the AET.
Section snippets
Experimental methods
Experiments were performed on male Syrian golden hamsters (Mesocricetus auratus), acclimatized at 20 ± 1 °C, with 12 h cycles day/night, with light from 06:00 to 18:00. On the 21st day after birth, they were randomly divided into two groups, one had the drinking water substituted by 10% fructose solution (Fructose, n = 54) and the other one was kept drinking filtered water (Control, n = 54) during 20 weeks thereafter. In the 16th week, each group was further subdivided into 2 subgroups: sedentary [no
Results
One hundred and eight animals entered into this study and were randomly assigned to two experimental groups: Control [C (n = 54)] and Fructose [F (n = 54)], and at a later time, subdivided into two different protocols, sedentary or exercised: Sedentary control [C (n = 27)]; Exercised Control [EC (n = 27)], Sedentary Fructose [F (n = 27)] and Exercised Fructose [EF (n = 27)].
Discussion
Our initial hypothesis was confirmed since increased ischemia/reperfusion induced microvascular permeability and endothelial dysfunction elicited by the substitution of drinking water by 10% fructose solution was significantly attenuated by chronic light/moderate aerobic exercise training program (AET).
In order to evaluate AET's effects, the chosen microcirculatory assessment technique was the cheek pouch preparation. This preparation represents a trustworthy technique since it displays robust,
Acknowledgments
The authors would like to thank Mr. Claudio N. Ribeiro and Mr. Paulo José F. Lopes for their help with animal care. Financial support was provided by the National Research Council of Brazil (CNPq) and the Foundation to Support Research in the Rio de Janeiro State (FAPERJ).
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