Increased leptin storage with altered leptin secretion from adipocytes of rats with sucrose-induced dyslipidemia and insulin resistance: effect of dietary fish oil

This study examined the effect of long-term feeding a high-sucrose diet (SRD) on the modulation of rat adipocyte's leptin secretion and storage. For this purpose, we analyzed (a) basal and insulin-stimulated leptin release and the role of isoproterenol and palmitate on insulin-stimulated leptin secretion, (b) the correlation between leptin and glycerol released, (c) the relationship between leptin contents and adiposity, and (d) the effect of fish oil (FO) administration on the above parameters. Wistar rats were fed an SRD for 6 months. Whereas half the animals continued with SRD up to month 8, the other half was fed an SRD in which FO partially replaced corn oil from months 6 to 8. Total leptin release was reduced both basally and under insulin stimulation in SRD-fed rats. However, the ratio of leptin released after hormone stimulation to basal leptin levels was similar in the 3 dietary groups. Isoproterenol inhibited insulin-stimulated leptin release in the 3 groups, but the percentage was lower in the SRD. Palmitic acid mimicked the effect of isoproterenol. Leptin release from adipocyte of SRD-fed rats negatively correlated with glycerol release. Leptin store increased in fat pads of SRD and positively correlated with adiposity. Fish oil reduced leptin content and fat pad hypertrophy, and normalized basal lipolysis, leptinemia, and glucose homeostasis. This suggests that enhanced lipolysis and altered insulin sensitivity could play a role in the decrease of leptin released in SRD-fed rats. This is consistent with the reversion of all the alterations after FO administration.Fil: Selenscig, Dante Alejandro. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Rossi, Andrea. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Chicco, Adriana Graciela. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Lombardo, Yolanda B.. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Dietary fish oil ameliorates adipose tissue dysfunction in insulin-resistant rats fed a sucrose-rich diet improving oxidative stress, peroxisome proliferator-activated receptor γ and uncoupling protein 2

This work aimed to assess the possible beneficial effects of dietary fish oil (FO) on the preexisting adipose tissue dysfunction through the improvement or reversion of the mechanisms underlying oxidative stress and pro-inflammatory cytokines in dyslipemic insulin-resistant rats. Wistar rats were fed a sucrose rich diet (SRD) for 6 months. After that half of the animals continued with the SRD until month 8 while in the other half corn oil was replaced by FO for 2 months (SRD+FO). A reference group consumed a control diet all the time. In epididymal fat pad we analyzed: antioxidant and oxidant enzymes activities; ROS content and glutathione redox state; the protein level of peroxisome proliferator-activated receptor gamma (PPARγ) and the expression and protein levels of uncoupling protein 2 (UCP2) as well as oxidative stress biomarkers and TNF-α and IL-6 plasma levels. Besides, insulin sensitivity and the composition of fatty acid phospholipids of adipose tissue were measured. Compared with the SRD the SRD+FO fed group showed a decrease of fat pad weight and the antioxidant and oxidant enzyme activities and ROS content returned to control values as well as plasma TNF-α and IL-6 levels. FO normalized both the decrease of PPARγ protein and the increase of protein and expression of UCP2. Furthermore, FO increased n-3/n-6 fatty acids ratio in the adipose tissue phospholipids and normalized dyslipidemia and insulin resistance. Finally, these findings reinforce the view that dietary FO may exert a beneficial effect in ameliorating the dyslipidemia and insulin resistance in this animal model.Fil: Selenscig, Dante Alejandro. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Ciencias Biológicas. Cátedra de Química Biológica; ArgentinaFil: Ferreira Cordoneda, Maria del Rosario. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Ciencias Biológicas. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Chicco, Adriana Graciela. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Ciencias Biológicas. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Bolzon, Yolanda Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Ciencias Biológicas. Cátedra de Química Biológica; Argentin

Time course of adipose tissue dysfunction associated with antioxidant defense, inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats

The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated following the time course of the development of oxidative stress, changes in proinflammatory cytokines and adiponectin levels, and their relationship with insulin resistance. We analyzed the morphometric characteristics of epididymal adipocytes, de novo lipogenesis enzyme activities and cellular antioxidant defense, inflammatory mediators, adiponectin levels and insulin resistance in rats fed a sucrose-rich diet for 3, 15 or 30 weeks and compared to those fed a control diet. The results showed a depletion of antioxidant enzyme activities in the fat pads of rats fed a sucrose-rich diet, with an increase in xanthine oxidase activity and lipid peroxidation after 3, 15 and 30 weeks on the diet. Superoxide dismutase activity and the redox state of glutathione showed a significant decrease at weeks 15 and 30. This was accompanied by visceral adiposity and enhanced lipogenic enzyme activities. An increase in the plasma levels of proinflammatory markers (TNF-α and IL-6) was recorded only after 30 weeks on the diet. A reduction in plasma adiponectin levels accompanied the time course of deterioration of whole-body insulin sensitivity. The results suggest that lipid peroxidation, depletion of antioxidant defenses and changes in inflammatory cytokines induced by a sucrose-rich diet contribute to the dysregulation of adipose tissue and insulin resistance. Finally, these results show that the progressive deterioration of adipose tissue function, which begins in the absence of both visceral adiposity and overweight, is highly dependent on the length of time on the diet.Fil: D'alessandro, Maria Eugenia Guadalupe. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Selenscig, Dante Alejandro. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Illesca, Paola Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Chicco, Adriana Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Lombardo, Yolanda B.. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Dietary soy protein improves adipose tissue dysfunction by modulating parameters related with oxidative stress in dyslipidemic insulin-resistant rats

The present study investigates the benefits of the dietary intake of soy protein on adipose tissue dysfunction in a rat model that mimics several aspects of the human metabolic syndrome. Wistar rats were fed a sucrose-rich diet (SRD) for 4 months. After that, half of the animals continued with SRD until month 8 while in the other half, casein protein was replaced by isolated soy protein for 4 months (SRD-S). A reference group consumed a control diet all the time. In adipose tissue we determined: i) the activities of antioxidant enzymes, gene expression of Mn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glutathione redox state ii) the activity of xanthine oxidase (XO), ROS levels and the gene expression of NAD(P)H oxidase iii) the expression of the nuclear factor erythroid-2 related factor-2 (Nrf2). Besides, adiposity visceral index, insulin sensitivity, and tumor necrosis factor-α (TNF-α) in plasma were determined. Compared with the SRD-fed rats, the animals fed a SRD-S showed: activity normalization of SOD and glutathione reductase, improvement of mRNA SOD and normalization of mRNA GPx without changes in the expression of the Nrf2, and improvement of glutathione redox state. These results were accompanied by a normalization of XO activity and improvement of both the ROS production as well as TNF-α levels in plasma. Besides, adipocyte size distribution, adiposity visceral index and insulin sensitivity improved. The results suggest that soy protein can be a complementary nutrient for treating some signs of the metabolic syndrome.Fil: Illesca, Paola Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Alvarez, Silvina Monica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Selenscig, Dante Alejandro. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Ferreira Cordoneda, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Gimenez, Maria Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Bolzon, Yolanda Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: D'alessandro, Maria Eugenia Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin