Efeitos nutracêuticos da curcumina e/ou do treinamento físico sobre morfologia e função do tecido adiposo marrom em ratas diabéticas ovariectomizadas

Abstract

Objective: To evaluate the effects of curcumin and physical exercise on morphological and functional parameters in brown adipose tissue of diabetic and ovariectomized Wistar rats. Methods: Twenty-four femele rats were divided into four experimental groups: sedentary (DOS), trained (DOT), sedentary treated with curcumin (DOS+CUR), and trained treated with curcumin (DOT+CUR). Diabetes mellitus type 1 was induced by streptozotocin (40mg/kg) and estrogenic restriction by bilateral ovariectomy surgeries. Nutraceutical curcumin was administered diluted in natural yogurt by gavage (100 mg/kg/day) and a moderate-intensity treadmill running protocol, five days a week, for eight weeks. At the end of the experiment, brown adipose tissue (BAT) and retroperitoneal (TAR), parametrial (TAP), mesenteric (TAME), and subcutaneous (TASC) white adipose tissue depots were removed and weighed. Morphological, histochemical, biochemical, and gene expression analyses were performed on TAM. Normality and homogeneity of data were assessed by the Shapiro-Wilk and Bartlett tests, respectively. The effects of treatments on the parameters studied were analyzed using a two-way ANOVA analysis, followed by multiple comparisons performed using Tukey's post hoc test. The significance level adopted was 5% (p ≤ 0.05) using the GraphPad Prism® statistical software, version 8.0. Results: The interaction between physical training and curcumin (DOT+CUR) promoted a significant increase in BAT, TAR, and TASC adipose tissue depots. Brown adipose tissue, despite not present mass alterations, showed variation in morphometry with a higher percentage of multilocular adipocytes and a lower percentage of unilocular adipocytes per field between the groups treated with curcumin or training and an increase in the total number of adipocytes and a reduction in the lipid area in the groups treated with curcumin. In the redox profile of BAT, a significant reduction in the levels of TBARS and nitrite was observed in the DOS+CUR and DOT groups when compared to the DOS group. These data were confirmed by the increase in immunostaining of the antioxidant enzymes HO-1, SOD-1 in the sedentary and trained groups supplemented with curcumin. Immunostaining for nuclear factor erythroid 2-related factor 2 (NRF2) increased in the DOS+CUR and DOT+CUR groups with significant interaction (p=0.0197). In contrast, immunostaining for nuclear factor κB (NF-κB), which is related to inflammation, was reduced in the groups treated with curcumin (DOS+CUR, DOT+CUR), and in the trained control group (DOT) (p=0.03). Regarding immunostaining for uncoupling protein 1 (UCP-1), a marker of thermogenesis and mitochondrial activity, an increase was observed following treatment with curcumin (p<0.0001) and training (p<0.0001). The enzymatic activities of the enzymes catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) increased with curcumin treatment, while exercise alone also increased GPx and SOD, for these enzymes the interaction was significant (p = 0.0001 and p = 0.0038 respectively). Finally, gene expression analysis of peroxisome proliferator-activated receptor g coactivator 1a (PGC-1a) revealed a main effect of curcumin (p < 0.0001) in the DOS + CUR and DTO + CUR groups compared to their controls, and in the expression of sirtuin 1 (SIRT-1) effects of curcumin (p = 0.0259) and training (p = 0.0155). The expression of IGF-1 (p < 0.0001) was reduced in the sedentary and trained groups treated with curcumin (p = 0.0001). Conclusion: Treatments with curcumin and physical exercise promoted effects in preserving body adiposity and improving the morphology and functionality of brown adipose tissue, activating antioxidant, anti- inflammatory, and thermogenic pathways, and mitochondrial biogenesis markers in rats with type I diabetes and ovariectomized. These effects may constitute important alternative pathways for preserving energy homeostasis and preventing thermogenic dysfunctions associated with BAT whitening in the model studied.