High dietary fructose load aggravates lipid metabolism in the liver of Wistar rats through imbalance between lipogenesis and fatty acid oxidation

Fructose ingestion is often associated with hepatic steatosis and hypertriglyceridemia. The homeostasis of hepatic lipids is mainly determined by the interplay of lipogenesis and fatty acid β‑oxidation. In this study, we hypothesized that high fructose intake disturbs hepatic lipid metabolism through an imbalance between these processes. Therefore, we analyzed the effects of a 9-weeklong consumption of a 60% fructose solution on physiological parameters, glycemia, and blood lipid profiles in male Wistar rats. The expression of key regulators of fatty acid oxidation (FAO) and lipogenesis in the liver were assessed by western blot and quantitative polymerase chain reaction. The results showed that fructose-fed rats were normoglycemic and hypertriglyceridemic with visceral adiposity, but without hepatic lipid deposition. A high-fructose diet is associated with increased nuclear levels of the lipogenic regulator sterol regulatory element binding protein 1c (SREBP-1c), which was followed by increased acetyl‑CoA carboxylase and fatty acid synthase mRNAs. The nuclear level of the FAO transcriptional regulators peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1) and lipin‑1 were unaltered, while carnitine palmitoyltransferase 1 (CPT1) mRNA was significantly decreased. Overall, our findings showed that liquid fructose overconsumption is associated with perturbation of hepatic lipid metabolism through predominance of lipogenesis over β-oxidation, resulting in spillover of triglycerides and visceral adiposity.Turkish Journal of Biology (2016), 40(6): 1235-124

Fructose-enriched diet affects hepatic lipid metabolism in young male and female rats in different ways

An increase in fructose consumption coincides with a rising incidence of metabolic disorders. Dietary fructose has been shown to affect hepatic lipid metabolism in a way that may lead to lipid deposition in the liver. In this study, we tested the hypothesis that the effects of fructose overconsumption on hepatic lipid metabolism differ between sexes. To that end we examined the effects of a high-fructose diet on the expression of key enzymes and transcription factors involved in the regulation of fatty acid oxidation and de novo lipogenesis in the liver of 12-week-old male and female Wistar rats. Immediately after weaning, the rats were subjected to a standard diet and 10% fructose solution or drinking water for 9 weeks. The fructose-enriched diet induced hypertriglyceridemia and increased hepatic de novo lipogenesis in both sexes, without lipid deposition in the liver. At the same time, visceral adiposity was observed only in female rats, while in males the treatment stimulated hepatic fatty acid oxidation. The fructose-enriched diet induced sex-specific effects on hepatic lipid metabolism in young rats. These results imply that male and female rats employ different strategies to cope with dietary fructose-related energy overload and to avoid lipid accumulation in the liver

Validation of endogenous controls for gene expression studies in peripheral lymphocytes from war veterans with and without PTSD

<p>Abstract</p> <p>Background</p> <p>Selection of appropriate endogenous control is a critical step in gene expression analysis. The aim of this study was to evaluate expression stability of four frequently used endogenous controls: β-actin, glyceraldehyde-3-phosphate dehydrogenase, β₂-microglobulin and RNA polymerase II polypeptide A in peripheral blood mononuclear cells from war veterans with and without posttraumatic stress disorder (PTSD). The study was designed as to identify suitable reference gene(s) for normalization of gene expression in peripheral blood mononuclear cells in response to war trauma and/or PTSD.</p> <p>Results</p> <p>The variability in expression of the four endogenous controls was assessed by TaqMan Real-time RT-PCR in peripheral blood mononuclear cells from: war veterans with current PTSD, those with lifetime PTSD, trauma controls and healthy subjects. Expression stability was analyzed by GeNorm and NormFinder software packages, and by direct comparison of Ct values. Both, GeNorm and NormFinder identified β-actin and glyceraldehyde-3-phosphate dehydrogenase as a pair of genes with the lowest stability value.</p> <p>Conclusions</p> <p>The combination of β-actin and glyceraldehyde-3-phosphate dehydrogenase appeared to be the most suitable reference for studying alterations in gene expression in peripheral blood mononuclear cells related to vulnerability and resilience to PTSD, as well as to trauma-provoked developing of this disorder and recovery from it. Using glyceraldehyde-3-phosphate dehydrogenase, β-actin and β_2-microglobulin as individual endogenous controls would provide satisfactory data, while RNA polymerase II polypeptide A could not be recommended.</p

Glucocorticoid-mediated effects of mif deficiency and fructose - enriched diet on energy metabolism in the mouse liver

Introduction: The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in the regulation of energy metabolism and glucocorticoid action in the liver. Genetic deletion of Mif may contribute to the development of systemic insulin resistance, especially in the setting of fructose overload that can be associated with perturbed hepatic metabolism. The aim: The aim of the present study was to elucidate the impact of combined effects of Mif deficiency and dietary sugar on energy metabolism and insulin sensitivity in the liver of male mice. Methods: Wild type (WT) and Mif deficient (MIF-/-) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on energy intake, and indicators of insulin sensitivity and glucocorticoid receptor (GR) signaling. Deregulation of Akt signaling pathway was used as a hallmark of hepatic insulin resistance. Changes in energy metabolism were estimated by AMP-activated protein kinase (AMPK) and SIRT1 protein levels. Results: All fructose-fed animals had increased energy intake, while elevated APMK and SIRT1 protein levels compared to the WT ones. Although enhanced glucocorticoid prereceptor metabolism was observed in all fructose-fed mice, GR protein level was increased only in MIF-/- animals. Mif deficient animals exibited impaired systemic insulin sensitivity. However, the impaired hepatic insulin signaling, revealed by decreased pAkt/total Akt ratio, was observed only in fructose-fed MIF-/- animals. Conclusion: The results showed that Mif deficiency under the conditions of dietary fructose overload leads to systemic insulin resistance, and impaired hepatic insulin signaling and energy metabolism, possibly through enhanced glucocorticoid signaling.Đorđević A, editor. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018; Petnica, Serbia. Belgrade: nstitute for Biological Research “Siniša Stanković”; 2018. p. 17

HSP70 level in the leaves of Phaseolus vulgaris intoxicated with cadmium.

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Gender modulates development of the metabolic syndrome phenotype in fructose-fed rats

We analyzed the effects of a fructose-rich diet (FRD) to test the assumption that the expression of metabolic syndrome phenotype is different in male and female rats. Two-way ANOVA revealed a significant effect of FRD on feeding behavior and carbohydrate/lipid metabolism. The increased caloric intake in FRD rats of both sexes was followed by a cluster of gender-specific changes typical for the metabolic syndrome. Female rats were characterized by decreased glycemia, increased triglycerides, enlarged visceral adipose tissue and increased absolute mass of liver, without changes in systolic blood pressure and insulin sensitivity. In contrast, male rats developed less disturbances in physical and biochemical characteristics, but blood pressure and insulin sensitivity were impaired by FRD. The results emphasize the detrimental effects of fructose consumption on cardiovascular risk and insulin action in males, whereas females are affected by other metabolic disturbances. These results support the idea of gender-dependent differences in the expression of the metabolic syndrome phenotype.Projekat ministarstva br. 4100

Gojaznost i reproduktivna funkcija žene - mehanizmi nastanka i terapijske implikacije

Gojaznost se danas smatra uzrokom nastanka kardiovaskularne bolesti, tipa 2 dijabetesa, osteoartritisa, maligniteta, ali i faktorom koji doprinosi nastanku reproduktivnih poremećaja i problema plodnosti. Postoji povećan relativni rizik za nastanak anovulatornog infertiliteta u žena sa izraženom gojaznošću i produženo vreme do koncepcije. U žena u reproduktivnom periodu gojaznost je povezana sa povećanim rizikom za nastanak hiperandrogenizma i anovulacije, kao što je slučaj u sindromu policističnih jajnika (PCOS) kao najčešćem hiperandrogenom poremećaju. Postoji veliki broj dokaza u prilog postojanja bliskog odnosa adipokina, gojaznosti, metaboličkog sindroma i reproduktivnih posledica. Redukcija težine za 5-10% dovodi do poboljšanja u kliničkim, metaboličkim i reproduktivnim karakteristikama, kao što je slučaj u žena sa PCOS. Primena insulinskih senzitajzera vodi sniženju hiperinsulinemije, insulinske rezistencije, uspostavljanju normalne menstrualne cikličnosti i ovulacije kod značajnog broja žena sa PCOS. Gojaznost može uticati na stimulaciju ovulacije njenim produžavanjem, povećanjem doze gonadotropina, incidence folikularne asinhronije i prekida stimulacije. Hirurško lečenje gojaznosti predstavlja alternativni vid terapije u slučaju kada ni promena načina života ni farmakoterapijske mere ne daju povoljne rezultate. Za sada ne postoji dovoljno dokaza u prilog preporuke da se barijatrijska hirurgija koristi u lečenju gojaznih žena sa PCOS.Projekat ministarstva br. 175032 i br. 4100

Gender modulates development of the metabolic syndrome phenotype in fructose-fed rats

We analyzed the effects of a fructose-rich diet (FRD) to test the assumption that the expression of metabolic syndrome phenotype is different in male and female rats. Two-way ANOVA revealed a significant effect of FRD on feeding behavior and carbohydrate/lipid metabolism. The increased caloric intake in FRD rats of both sexes was followed by a cluster of gender-specific changes typical for the metabolic syndrome. Female rats were characterized by decreased glycemia, increased triglycerides, enlarged visceral adipose tissue and increased absolute mass of liver, without changes in systolic blood pressure and insulin sensitivity. In contrast, male rats developed less disturbances in physical and biochemical characteristics, but blood pressure and insulin sensitivity were impaired by FRD. The results emphasize the detrimental effects of fructose consumption on cardiovascular risk and insulin action in males, whereas females are affected by other metabolic disturbances. These results support the idea of gender-dependent differences in the expression of the metabolic syndrome phenotype.Projekat ministarstva br. 4100

Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of superoxide dismutase and decreased metallothionein level, while rendering the level of copper importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi network unaffected. Stress had no effect on renal copper metabolism. The activity and expression of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose, independently of stress, decreased renal copper level, and modulated renal copper metabolism as to preserve vital cellular function including mitochondrial energy production and antioxidative defense, at the expense of intracellular copper storage