Oestradiol Treatment Counteracts the Effect of Fructose-Rich Diet on Matrix Metalloproteinase 9 Expression and NF kappa B Activation

Fructose-rich diet induces metabolic changes similar to those observed in metabolic syndrome. Among other matrix metalloproteinases, MMP-9 has an important role in adverse cardiac remodelling and might have a role in the development of cardiovascular disorders associated with metabolic syndrome. The changes of MMP-9 expression could be mediated via the NF kappa B pathway. In this study we investigated the effect of fructose-rich diet on MMP-9 expression in the heart of male and female rats, along with the effect of fructose-rich diet and oestradiol on MMP-9 expression in ovariectomized females. We further assessed the effect of fructose-rich diet and oestradiol on NF kappa B activation, measured as the level of p65 phosphorylation at Ser 276. The results showed that the diet regime did not affect the heart mass. Higher MMP-9 gene expression was found in cardiac tissue of male rats fed the fructose-rich diet than in females on the same diet regime. In ovariectomized females, fructose-rich diet upregulated MMP-9 protein and mRNA expression in the heart, as well as phosphorylation of the p65 subunit of NF kappa B at Ser 276. Oestradiol replacement therapy reverted these changes in the heart of ovariectomized females. This study has shown that oestradiol could revert the early molecular changes in MMP-9 expression induced by fructose-rich diet that occurred before cardiac hypertrophy development by decreasing phosphorylation of the NF kappa B p65 subunit at Ser 276

Improvement of lipid metabolism regulation by low-intensity exercise in fructose-fed rats

Excessive dietary fructose consumption in parallel with limited physical activity contributes to the global increase in prevalence of metabolic disorders. Metabolic syndrome represents a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia, and it is undoubtedly linked to increased risk for two global maladies, type 2 diabetes, and cardiovascular diseases. Fructose-rich diet is accompanied by the development of insulin resistance in the heart, and it could change the use of cardiac energy substrates towards increased fatty acid (FA) uptake, and catabolism. Exercise may be beneficial in prevention and treatment of the metabolic syndrome. The aim of this study was to analyse the impact of low-intensity exercise on protein expression of nuclear transcription factors involved in regulating FA β- oxidation in a heart of fructose fed rats. Male Wistar rats were divided into control group, and two groups that received 10% fructose for 9 weeks, one which was sedentary and one which was additionally exposed to low intensity exercise. The protein expression of important transcriptional regulators of fatty acid β-oxidation PPARα, and FOXO1, and coregulators Lipin1, PGC-1, and SIRT1 are analyzed in cardiac lysate and/or nuclear fraction by Western blot. Gene expression of ACADL, the enzyme that catalyzes the initial step of mitochondrial β-oxidation, was quantified by real-time PCR. Fructose-rich diet decreased nuclear PPARα compared to control. Exercise increased nuclear PPARα, nuclear FOXO1, lysate PGC1, and nuclear Lipin1 in fructose-fed rats compared to sedentary fructose-fed rats. Exercise increased lysate PPARα, lysate and nuclear FOXO1, lysate PGC1, lysate and nuclear SIRT1, and nuclear Lipin1 in fructose-fed rats compared to control. In conclusion, running at low intensity is accompanied by increased expression of key regulators of fatty acid oxidation. The results indicate that exercise achieves its effect by increasing the nuclear content of PPARα, Lipin1, and FOXO1

Fructose-Rich Diet-Induced Changes in the Expression of the Renin Angiotensin System Molecules in the Heart of Ovariectomized Female Rats Could be Reversed by Estradiol

The renin-angiotensin system has been implicated in the development of metabolic syndrome and appears to be a key in the local tissue control of normal cardiac functions. Physiological concentrations of estrogens have been shown to be cardioprotective, especially against the damaging effects of fructose-rich diet. The aim of the study was to investigate the expression of the renin-angiotensin system molecules with potentially deleterious effect on the heart (angiotensin-converting enzyme and angiotensin II type 1 receptor) and those with potentially protective effects, (angiotensin-converting enzyme 2 and angiotensin II type 2 receptor), in ovariectomized fructose fed female rats with 17-estradiol replacement. Real-time PCR and Western blot analysis were used for quantification of gene and protein expression in the heart. Fructose diet increased the expression of angiotensin-converting enzyme and angiotensin II type 1 receptor and decreased the expression of angiotensin-converting enzyme 2 and angiotensin II type 2 receptor. On the other hand, estradiol replacement seems to undo fructose diet effects on cardiac renin-angiotensin system. Downregulation of angiotensin-converting enzyme and angiotensin II type 1 receptor, and reversion of expression of both potentially protective molecules, angiotensin-converting enzyme 2 and angiotensin II type 2 receptor, to the control level in cardiac tissue took place. Obtained results suggest that estradiol may reverse the harmful effect of fructose-rich diet on the expression of renin-angiotensin system molecules. These findings may also be important in further research of phenotypes like insulin resistance, metabolic syndrome, and following cardiovascular pathology in females

Consumption of walnuts suppresses the conversion of palmitic to palmitoleic acid and enhances omega-3 fatty acid metabolism in the heart of fructose-fed rats

Walnut consumption mostly has a positive implication for cardiovascular health. Walnut diet effects on the cardiac fatty acid (FA) metabolism of healthy rats and those with fructose diet-induced metabolic burden were analysed. Both walnuts and fructose increased CD36 transporter level and the nuclear content of some/all of Lipin 1/PPARα/PGC-1 complex partners, as well as cytosolic and nuclear FOXO1. However, fructose, independently of walnuts, increased the content of palmitic (PA), oleic, and vaccenic acid (VA), while in walnut-fed rats failed to increase palmitoleic acid (POA) level and the POA/PA ratio, as well as total MUFA content. In opposite, walnuts reduced the level of PA and VA and increased alpha-linolenic, eicosapentaenoic and docosapentaenoic acid level, regardless of fructose. In conclusion, both fructose and walnuts stimulated the uptake and oxidation of FA in the heart, but the walnuts, opposite to fructose, favourably altered cardiac FA profile in healthy and metabolically compromised rats.Ministry of Education, Science and Technological Development, Republic of Serbia12 month embargo; published online: 02 August 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Consumption of walnuts suppresses the conversion of palmitic to palmitoleic acid and enhances omega-3 fatty acid metabolism in the heart of fructose-fed rats

Walnut consumption mostly has a positive implication for cardiovascular health. Walnut diet effects on the cardiac fatty acid (FA) metabolism of healthy rats and those with fructose diet-induced metabolic burden were analysed. Both walnuts and fructose increased CD36 transporter level and the nuclear content of some/all of Lipin 1/PPARα/PGC-1 complex partners, as well as cytosolic and nuclear FOXO1. However, fructose, independently of walnuts, increased the content of palmitic (PA), oleic, and vaccenic acid (VA), while in walnut-fed rats failed to increase palmitoleic acid (POA) level and the POA/PA ratio, as well as total MUFA content. In opposite, walnuts reduced the level of PA and VA and increased alpha-linolenic, eicosapentaenoic and docosapentaenoic acid level, regardless of fructose. In conclusion, both fructose and walnuts stimulated the uptake and oxidation of FA in the heart, but the walnuts, opposite to fructose, favourably altered cardiac FA profile in healthy and metabolically compromised rats

Low-intensity exercise diverts cardiac fatty acid metabolism from triacylglycerol synthesis to beta oxidation in fructose-fed rats

Context: Excessive fructose consumption causes ectopic lipid storage leading to metabolic disorders and cardiovascular diseases associated with defective substrate utilisation in the heart. Objective: Examining the preventive impact of low-intensity exercise on alterations related to fructose-rich diet (FRD) on cardiac fatty acid (FA) transport and metabolism. Materials and methods: Male Wistar rats were divided into control and two groups that received 10% fructose for 9 weeks, one of which was additionally exposed to exercise. Results: FRD elevated plasma and cardiac TAG, FATP1 in plasma membrane, Lipin 1 in microsomes and HSL mRNA, while mitochondrial CPT1 was decreased. Exercise decreased plasma free FA level, raised CD36 in plasma membrane and FATP1 in lysate, mitochondrial CPT1 and decreased microsomal Lipin 1 in fructose-fed rats. Conclusions: FRD changed plasma lipids and augmented partitioning of FA to TAG storage in the heart, whereas exercise in FRD rats switched metabolism of FA towards β-oxidation

Cholecalciferol affects cardiac proteins regulating malonyl-CoA availability and intracellular calcium level

Cholecalciferol improves insulin signaling and glucose metabolism in the heart and reduces circulating non-esterified fatty acids. Cholecalciferol effects on the cardiac fatty acid (FA) metabolism and the consequences on calcium handling were examined. Blood lipid profile was determined. Western blot and qRT-PCR were used to examine protein and mRNA expression. Cholecalciferoltreated rats had increased acetyl CoA carboxylase 2 protein expression and decreased expression of malonyl CoA decarboxylase. In addition, the expression of uncoupling protein 3 was elevated. Also, the level of peroxisome proliferator-activated receptor-gamma coactivator in the nucleus of heart cells was increased along with the level of sarcoplasmic/endoplasmic reticulum Ca2+ATPase in the microsomal fraction. In parallel, the L-type calcium channel and ryanodine receptor expression was reduced. In the heart of healthy rats, cholecalciferol affects proteins regulating malonyl CoA availability and intracellular Ca2+ handling proteins

The effects of low‐intensity exercise on cardiac glycogenesis and glycolysis in male and ovariectomized female rats on a fructose‐rich diet

We previously reported that low-intensity exercise prevented cardiac insulin resistance induced by a fructose-rich diet (FRD). To examine whether low-intensity exercise could prevent the disturbances of key molecules of cardiac glucose metabolism induced by FRD in male and ovariectomized (ovx) female rats, animals were exposed to 10% fructose solution (SF) or underwent both fructose diet and exercise (EF). Exercise prevented a decrease in cardiac GSK-3β phosphorylation induced by FRD in males (p <.001 vs. SF). It also prevented a decrease in PFK-2 phosphorylation in ovx females (p <.001 vs. SF) and increased the expression of PFK-2 in males (p <.05 vs. control). Exercise did not prevent a decrease in plasma membrane GLUT1 and GLUT4 levels in ovx females on FRD. The only effect of exercise on glucose transporters that could be indicated as beneficial is an augmented GLUT4 protein expression in males (p <.05 vs. control). Obtained results suggest that low-intensity exercise prevents harmful effects of FRD towards cardiac glycogenesis in males and glycolysis in ovx females. Practical applications: Low-intensity exercise, equivalent to brisk walking, was able to prevent disturbances in cardiac glycolysis regulation in ovx female and the glycogen synthesis pathway in male rats. In terms of human health, although molecular mechanisms of beneficial effects of exercise on cardiac glucose metabolism vary between genders, low-intensity running may be a useful non-pharmacological approach in the prevention of cardiac metabolic disorders in both men and postmenopausal women. © 2021 Wiley Periodicals LLC

Low-Intensity Exercise Affects Cardiac Fatty Acid Oxidation by Increasing the Nuclear Content of PPARα, FOXO1, and Lipin1 in Fructose-Fed Rats

Background and Aim: Excessive fructose consumption along with a sedentary lifestyle provokes metabolic disorders and cardiovascular diseases. Fructose overload causes cardiac insulin resistance and increases reliance on fatty acid (FA) uptake and catabolism. The cardiometabolic benefits of exercise training have long been appreciated. The goal of the presented study is to shed a new light to the preventive role of exercise training on cardiac lipid metabolism in fructose-fed rats. Methods: Male Wistar rats were divided into control (C), sedentary fructose (F), and exercised fructose (EF) groups. Fructose was given as a 10% fructose solution in drinking water for 9 weeks. Low-intensity exercise training was applied for 9 weeks. The protein expression and subcellular localization of Lipin1, peroxisome proliferator-activated receptor α (PPARα), and peroxisome proliferator-activated receptor-γcoactivator 1 α (PGC1) were analyzed in the heart using Western blot. Cardiac forkhead box transcription factor 1 (FOXO1) and sirtuin 1 (SIRT1) protein levels were also evaluated. Gene expression of long-chain acyl-CoA dehydrogenase was analyzed by quantitative polymerase chain reaction. Results: Exercise training has augmented the expression of main regulators of FA oxidation in the heart and achieves its effect by increasing the nuclear content of PPARα, Lipin1, and FOXO1 compared with the fructose group (P = 0.0422, P = 0.000045, P = 0.00958, respectively). In addition, Lipin1, FOXO1, and SIRT1 were increased in nuclear extract after exercise compared with the control group (P = 0.000043, P = 0.0417, P = 0.0329, respectively). In cardiac lysate, low-intensity exercise caused significantly increased protein level of PPARα, PGC1, FOXO1, and SIRT1 compared with control (P = 0.0377, P = 0.0275, P = 0.0096, P = 0.0282, respectively) and PGC1 level compared with the fructose group (P = 0.0417). Conclusion: The obtained results imply that the heart with a metabolic burden additionally relies on FA as an energy substrate after low-intensity running. © Copyright 2023, Mary Ann Liebert, Inc., publishers 2023