High fructose exposure modifies the amount of adipocyte-secreted microRNAs into extracellular vesicles in supernatants and plasma (original) (raw)
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Frontiers in Cell and Developmental Biology, 2023
Dietary high fructose (HFrD) is known as a metabolic disruptor contributing to the development of obesity, diabetes, and dyslipidemia. Children are more sensitive to sugar than adults due to the distinct metabolic profile, therefore it is especially relevant to study the metabolic alterations induced by HFrD and the mechanisms underlying such changes in animal models of different ages. Emerging research suggests the fundamental role of epigenetic factors such as microRNAs (miRNAs) in metabolic tissue injury. In this perspective, the aim of the present study was to investigate the involvement of miR-122-5p, miR-34a-5p, and miR-125b-5p examining the effects induced by fructose overconsumption and to evaluate whether a differential miRNA regulation exists between young and adult animals. We used young rats (30 days) and adult rats (90 days) fed on HFrD for a short period (2 weeks) as animal models. The results indicate that both young and adult rats fed on HFrD exhibit an increase in systemic oxidative stress, the establishment of an inflammatory state, and metabolic perturbations involving the relevant miRNAs and their axes. In the skeletal muscle of adult rats, HFrD impair insulin sensitivity and triglyceride accumulation affecting the miR-122-5p/PTP1B/P-IRS-1(Tyr612) axis. In liver and skeletal muscle, HFrD acts on miR-34a-5p/SIRT-1: AMPK pathway resulting in a decrease of fat oxidation and an increase in fat synthesis. In addition, liver and skeletal muscle of young and adult rats exhibit an imbalance in antioxidant enzyme. Finally, HFrD modulates miR-125b-5p expression levels in liver and white adipose tissue determining modifications in de novo lipogenesis. Therefore, miRNA modulation displays a specific tissue trend indicative of a regulatory network that contributes in targeting genes of various pathways, subsequently yielding extensive effects on cell metabolism.
BioMed Research International, 2016
Circulating microRNAs (miRNAs) and the functional implications of miRNAs contained in extracellular vesicles (EVs) have gained attention in the last decade. Little is known about the regulation of the abundance of plasma miRNAs in response to chronic ingestion of carbohydrates. Therefore, we explored the circulating levels of miR-21, miR-146a, miR-155, and miR-223 in rats consuming sucrose in drinking water. Weanling Wistar rats were 25 weeks with 30% sucrose in drinking water, and miRNAs expression was determined in total plasma and in microvesicles, by RT-qPCR with TaqMan probe based assays for miR-21, miR-146a, miR-155, and miR-223, using cel-miR-39 (as spike in control and reference). Endotoxemia was also measured. Sucrose-fed animals showed higher body weight and retroperitoneal adipose tissue as well as higher glucose and triglyceride plasma levels than controls. Plasma endotoxin levels were low and not different among groups. Plasma miR-21 and miR-223 were higher in the sucro...
Nutrients
Noncoding microRNAs are involved in lipid and carbohydrate metabolism pathways and are powerful regulators of gene expression. The goals of this study were to evaluate the temporal expression profiles of miRNAs in rat adipose tissue and predict mRNA–microRNA interactions. Newly weaned Wistar rats were divided into groups fed a standard diet and high-sucrose diet (HSD). The HSD contains 66.86% carbohydrates (40.45% standard diet, 40.45% condensed milk, and 8.58% crystal sugar), and the HSD was provided for 4, 8 and 15-week periods to investigate the expression levels of miRNAs in visceral adipose tissue using RT–qPCR. Target selection, enriched pathways and networks were analyzed in silico. The factor consumption time significantly was associated to decreases (p < 0.05) in the expression levels of the following miRNAs: 124-5p, 125-5p, 126-5p, 200c-3p, and 212-3p in all experimental groups. The factor diet significantly influenced rno-miR-124-5p, 200c-3p, and 212-3p expression (p &...
Total Plasma and in Extracellular Vesicles from Rats with Chronic Ingestion of Sucrose
Circulating microRNAs (miRNAs) and the functional implications of miRNAs contained in extracellular vesicles (EVs) have gained attention in the last decade. Little is known about the regulation of the abundance of plasma miRNAs in response to chronic ingestion of carbohydrates. Therefore, we explored the circulating levels of miR-21, miR-146a, miR-155, and miR-223 in rats consuming sucrose in drinking water. Weanling Wistar rats were 25 weeks with 30% sucrose in drinking water, and miRNAs expression was determined in total plasma and in microvesicles, by RT-qPCR with TaqMan probe based assays for miR-21, miR-146a, miR-155, and miR-223, using cel-miR-39 (as spike in control and reference). Endotoxemia was also measured. Sucrose-fed animals showed higher body weight and retroperitoneal adipose tissue as well as higher glucose and triglyceride plasma levels than controls. Plasma endotoxin levels were low and not different among groups. Plasma miR-21 and miR-223 were higher in the sucrose group (í µí± < 0.05), whereas miR-155 tended to be lower (í µí± = 0.0661), and miR-146a did not show significant differences. In the plasma EVs the same trend was found except for miR-146a that showed significantly higher levels (í µí± < 0.05). Overall, our results show that high carbohydrate ingestion modulates circulating miRNAs levels related to an inflammatory response.
Sains Malaysiana, 2018
Fructose is commonly used as a taste enhancer in many processed foods. Excessive fructose consumption is highly associated with obesity and development of cancer particularly prostate cancer. This study aimed to investigate the biochemical and molecular changes in the prostate tissue of rats treated with 20% fructose for six months. A total of 18 rats weighted 200-250 g were divided into two groups, where each group consisted of 9 rats. Control group is given normal diet, while the treated group was given normal diet and 20% fructose in drinking water. After six months of treatment, both groups were sacrificed for further analysis. Body weight, blood pressure and glucose were measured. Lipid profiles were determined using quantitative colorimetric assay. Transcripts level of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), leptin (LEP), angiopoietin 1 (ANGPT1), microRNA (miR)-34a, miR-10b and miR-192 were determined using quantitative PCR, while the protein levels of 11β-HSD1 and leptin were determined using ELISA. The results showed that 20% fructose diet significantly increased blood glucose level as compared to the control (p<0.05). The transcript levels of LEP and miR-192 were significantly lower in the fructose-treated group as compared to the control (p<0.05). There was a significant linear relationship between prostate LEP and serum LDL/VLDL level as well as between the level of prostate LEP and serum total cholesterol level (p<0.05). Thus, our results showed that chronic consumption of fructose could down-regulate LEP and miR-192 expression in prostate tissue, and promote higher accumulation of fat in the tissue. Additionally, downregulation of miR-192 has been reported to be associated with the pathogenesis of prostate cancer. Thus, it can be concluded that long-term fructose diet leads to higher blood glucose level and down-regulation of LEP and miR-192 expression in prostate tissue.
Extra fructose in the growth medium fuels lipogenesis of adipocytes
Journal of obesity, 2014
Fructose in excessive amounts exerts negative effects on insulin sensitivity, blood pressure, and liver metabolism. These adverse outcomes were attributed to its disturbances of key metabolic pathways in the liver. Recently, possible consequences of high fructose levels directly on adipocytes in vivo have been considered. We have cultured adipocytes in growth media containing 1 g/L fructose additionally to glucose and monitored the cells fate. Cells developed lipid vesicles much earlier with fructose and showed altered kinetics of the expression of mRNAs involved in lipogenesis and hexose uptake. Adiponectin secretion, too, peaked earlier in fructose containing media than in media with glucose only. From these data it can be speculated that similar effects of fructose containing diets happen in vivo also. Apart from toxic action on liver cells, adipocytes might be stimulated to take up extra fructose and generate new lipid vesicles, further dysregulating energy homeostasis.
The Destiny of Glucose from a MicroRNA Perspective
Frontiers in endocrinology, 2018
Glucose serves as a primary, and for some tissues the unique, fuel source in order to generate and maintain the biological functions. Hyperglycemia is a hallmark of type 2 diabetes and is the direct consequence of perturbations in the glucose homeostasis. Insulin resistance, referred to as a reduced response of target tissues to the hormone, contributes to the development of hyperglycemia. The molecular mechanisms responsible for the altered glucose homeostasis are numerous and not completely understood. MicroRNAs (miRNAs) are now recognized as regulators of the lipid and glucose metabolism and are involved in the onset of metabolic diseases. Indeed, these small non-coding RNA molecules operate in the RNA silencing and posttranscriptional regulation of gene expression and may modulate the levels of kinases and enzymes in the glucose metabolism. Therefore, a better characterization of the function of miRNAs and a deeper understanding of their role in disease may represent a fundament...
The Journal of Clinical Endocrinology & Metabolism, 2014
Context: type 2 diabetes is a chronic disease characterized by inadequate beta-cell response to the progressive insulin resistance. MicroRNAs (miRNAs) are short, endogenous, non-coding, RNAs representing a class of powerful gene expression modulators. Previous population studies observed a modulation of circulating miRNAs in diabetic patients; however, little data are presently available on miRNA modulation in diabetic patients naïve to pharmacological treatment, as well as the effect of glycemic control on this.
In Vitro Culture of Human Brown Adipocytes: Effects of Fructose
International Journal of Life Science and Medical Research, 2016
Brown adipocytes can be distinguished from their white counterparts by markers such as UCP-1 or P2RX5. This study cultured brown human adipocytes in growth media containing 0.1 g/L and 1 g/L fructose in addition to glucose and monitored the cell growth. Unexpectedly, the cultured cells co-expressed markers for white adipocytes (ASC-1) and markers for brown adipocytes (P2RX5). Cells developed multilocular lipid vesicles and exhibited similar kinetics of mRNAs involved in lipogenesis with and without fructose. Excessive amounts of fructose induce negative effects on insulin sensitivity, blood pressure, and liver metabolism. These adverse outcomes were attributed to disturbances in key metabolic pathways in the liver. However, possible consequences of high fructose levels when in direct contact with human white adipocytes in vivo have been considered. No such data existed on the effects of fructose on human brown adipocytes. Results indicate that in addition to toxic effects on liver cells, human white and brown adipocytes consume extra fructose and generate new lipid vesicles, further deregulating energy homeostasis.
Frontiers in Endocrinology
As mediators of intercellular communication, circulating extracellular vehicles (EVs) can modulate tissue and cellular pathways by altering transcription profiles in recipient cells, and their content may reflect the status of their parent cells. However, whether their cargo is altered in the metabolic syndrome (Mets) remains unclear. We hypothesized that MetS altered mRNAs and miRNAs packed within circulating-EVs. EVs were collected from plasma of patients with MetS or age-matched Lean controls (n=4 each). RNA sequencing was performed to identify dysregulated mRNAs and miRNAs, and analyze genes targeted by miRNAs, top pathways, and diseases associated with MetS-EVs. MetS patients showed elevated body weight, blood pressure, glucose, insulin, and liver injury markers levels. 1,446 mRNAs were downregulated and 32 upregulated in MetS- compared to Lean-EVs, whereas 40 miRNAs were selectively enriched and 10 downregulated in MetS-EVs. MetS upregulated in EVs genes involved in apoptosis,...