We studied the effect of feeding normal adult male rats with a commercial diet supplemented with fructose added to the drinking water (10% w/v; fructose-rich diet, FRD) on the adipogenic capacity of stromal-vascular fraction (SVF) cells isolated from visceral adipose tissue (VAT) pads. Animals received either the commercial diet or FRD ad libitum for 3 weeks; thereafter, we evaluated the in vitro proliferative and adipogenic capacities of their VAT SVF cells. FRD significantly increased plasma insulin, triglyceride and leptin levels, VAT mass/cell size, and the in vitro adipogenic capacity of SVF cells. Flow cytometry studies indicated that the VAT precursor cell population number did not differ between groups; however, the accelerated adipogenic process could result from an imbalance between endogenous pro-and anti-adipogenic SVF cell signals, which are clearly shifted towards the former. The increased insulin milieu and its intracellular mediator (insulin receptor substrate-1) in VAT pads, as well as the enhanced SVF cell expression of Zpf423 and peroxisome proliferator receptor-c2 (all pro-adipogenic modulators), together with a decreased SVF cell concentration of anti-adipogenic factors (pre-adipocyte factor-1 and wingless-type MMTV-10b), strongly supports this assumption. We hypothesize that the VAT mass expansion recorded in FRD rats results from the combination of initial accelerated adipogenesis and final cell hypertrophy. It remains to be determined whether FRD administration over longer periods could perpetuate both processes, or whether cell hypertrophy itself remains responsible for a further VAT mass expansion, as observed in advanced/morbid obesity.

In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

Hipótesis De la compleja red de interrelaciones entre angiogénesis y adipogénesis descripta, se deduce la interdependencia de ambos procesos. Para obtener evidencia experimental que la demuestre, se proponen los siguientes objetivos. Objetivo general Evaluar el efecto in vivo de la inhibición general de la angiogénesis sobre el tejido adiposo visceral y los procesos de proliferación y diferenciación de las CPA de su Fracción Estroma Vascular. Objetivos específicos 1. Desarrollar un modelo in vivo de inhibición farmacológica de la angiogénesis, verificando su efecto a los 15 días post-tratamiento. 2. Determinar la concentración de marcadores metabólicos y endocrinos circulantes que podrían afectar la función del tejido adiposo: glucosa, insulina, colesterol total, triglicéridos, NEFA, leptina y TBARS. 3. Evaluar los cambios morfológicos del TAV como resultado del tratamiento. 4. Evaluar el impacto del tratamiento sobre la capacidad proliferativa in vitro de las células de la FEV 5. Evaluar la expresión de marcadores de superficie de la población de células de la FEV en ambos grupos mediante citometría de flujo. 6. Evaluar las señales intracelulares con acción reguladora conocida sobre la angiogénesis y los procesos de proliferación y diferenciación adipocitaria, en tres estadios celulares: células de la FEV, células proliferadas in vitro sin diferenciar (día 0) y células proliferadas y diferenciadas in vitro (día 10).