RESUMEN
Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling.
RESUMEN
BACKGROUND: Metabolic imprinting describes associations between nutritional experiences of early life and the development of diseases later in life. The goal of this study was to evaluate the metabolic imprinting induced by a high-sugar diet (HSD) and its effects on microRNA (miRNA) expression and insulin resistance (IR) in young rats. We assessed the effects of expression of adipogenic (miR-200c) and metabolic (miR-126a) miRNAs in retroperitoneal white adipose tissue (rWAT) on IR development. METHODS AND RESULTS: Weaned male Wistar rats (N = 6) were fed a standard chow diet or HSD (68% carbohydrates) for 4-, 8-, or 12-weeks. Serum samples were collected to measure triacylglycerol and VLDL-cholesterol, and we assessed glucometabolic parameters (glucose, insulin, HOMA-IR, and QUICKI). rWAT was collected for microRNA analysis (N = 3). The HSD resulted in body fat accretion and IR after 8-weeks, which resolved by 12-weeks. Moreover, the HSD had a time-dependent effect on miRNA relative expression, downregulating rno-miR-200c-3p at week 8 and rno-miR-126a-3p at week 12. CONCLUSIONS: MiR-200 family dysregulation has been related to IR, and miR-126a downregulation could be associated with the improvement in IR observed after a 12-week HSD feeding period. This is the first time that excessive sugar intake post-weaning has been associated with miRNA production by rWAT with an impact on IR development.
Asunto(s)
Resistencia a la Insulina , MicroARNs , Animales , Dieta , Glucosa/metabolismo , Resistencia a la Insulina/genética , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Ratas WistarRESUMEN
INTRODUCTION: The intake of sugar-sweetened beverages (SSBs) has increased rapidly, but the effects of this habit on health and physical performance are unknown. This study assessed the effect of excessive SSB intake on biochemical, physical performance, and biochemical and cardiovascular parameters of physically active males. METHODS: Seventeen volunteers consumed a placebo drink (Pd; carbohydrate free) and an excessive SSB drink (eSSBd = Pd plus 300 g sucrose). In a blind randomized crossover study, the subjects were assigned to Pd or eSSBd groups for 15 days. After an interval of 7 days, subjects were reassigned to the other condition. RESULTS: After eSSBd intake, there was an increase in weight (69.34 ± 13.71 vs. 70.62 ± 14.06), body mass index (24.49 ± 4.01 vs. 24.97 ± 4.13), waist circumference (75.33 ± 11.22 vs. 76.79 ± 11.51), VLDL (19.54 ± 9.50 vs. 25.52 ± 11.18), triglycerides (78.94 ± 23.79 vs. 114.77 ± 43.65), and peak systolic blood pressure (178.57 ± 26.56 vs. 200.71 ± 24.64). The cardiorespiratory response to exercise (VO2max) (48.15 ± 10.42 vs. 40.98 ± 11.20), peak heart rate (186.64 ± 8.00 vs. 179.64 ± 6.28), total exercise time (15.02 ± 1.57 vs. 14.00 ± 2.18), and mechanical work (15.83 ± 4.53 vs. 13.68 ± 5.67) decreased after eSSBd intake (all values expressed in initial mean ± DP vs. final). The rates of perceived exertion were higher (1.300 vs.1.661 slope and -0.7186 vs. -1.118 y-intercept) after eSSBd intake. CONCLUSION: The present study shows that 15 days of eSSBd intake may negatively modulate biochemical parameters associated with cardiovascular risk. In addition, this overintake can impair the physical performance and cardiovascular responses to physical exercise.
RESUMEN
Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming without workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (without workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in Pgc1α expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming without workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis.