Quercetin decreases fructose drinking in model of fructose-induced insulin resistance. Unexpected uric acid and TBARS lowering effect of methyl cellulose vehicle and fructose combination.

The aim of this study was to improve insulin sensitivity in fructose-treated animals by ingestion of flavonoid quercetin. Several signs of insulin resistance have been developed in rats by drinking 10% fructose solution for 9 weeks. The effect of 6-week-gavage-administrated quercetin (20 mg/kg/day in 1% methyl cellulose solution) was monitored. Rats of the control groups received methyl cellulose vehicle as well. The most striking result of the quercetin treatment was the normalization of the fructose solution drinking to the level of drinking water intake. In addition, quercetin supplementation considerably decreased the plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index in rats consuming fructose. Surprisingly, fructose ingestion did not elevate plasma uric acid, thiobarbituric acid reactive substances, nitrotyrosine, or advanced glycation end products fluorescence. Instead, a reduction of the above parameters was observed. In summary, these results indicate that quercetin supplementation reduces fructose drinking and decreases plasma glucose and the HOMA-IR index. Furthermore, methyl cellulose, in combination with fructose, causes uric acid - lowering, antioxidant and anti-glycation effects. Thus, methyl cellulose possibly shifts fructose metabolism in favor of the utilization of antioxidant features of fructose. Our results call for using methyl cellulose in sweetened beverages and other sweetened food.

Effects of Walnut-Rich Diet on Cation-Handling Proteins in the Heart of Healthy and Metabolically Compromised Male Rats.

The transport of cations in the cardiomyocytes, crucial for the functioning of the heart, can be affected by walnut diet due to the high content of polyunsaturated fatty acids. Healthy and metabolically compromised rats (drinking 10% fructose solution) were subjected to a diet supplemented with 2.4 g of walnuts for 6 weeks to investigate the effect on proteins involved in cation transport in the heart cells. Fructose increased the level of the α1 subunit of Na+/K+-ATPase and the phosphorylation of extracellular signal-regulated kinase 1/2 in the heart of control and walnut-eating rats, while elevated L-type calcium channel α (LTCCα), sodium-calcium exchanger 1 (NCX1), and Maxi Kα level were observed only in rats that did not consume walnuts. However, walnuts significantly increased the cardiac content of LTCC, NCX1, and Maxi Kα, as well as Kir6.1 and SUR2B subunits of KATP channel, but only in fructose-naive rats. In animals that drank fructose, a significant increasing effect of walnuts was observed only in Akt kinase phosphorylation, which may be a part of the antiarrhythmic mechanism of decreasing cation currents in cardiomyocytes. The walnut diet-induced increase in LTCC and NCX1 expression in healthy rats may indicate intense cardiac calcium turnover, whereas the effect on Kir6.1 and SUR2B subunits suggests stimulation of KATP channel transport in the cardiac vasculature. The effects of walnuts on the cation-handling proteins in the heart, mostly limited to healthy animals, suggest the possible use of a walnut-supplemented diet in the prevention rather than the treatment of cardiological channelopathies.

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.

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-γ coactivator 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.

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 ß-oxidation.

Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart.

Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.

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.

Obesity-related prepartal insulin resistance in dairy cows is associated with increased lipin 1 and decreased FATP 1 expression in skeletal muscle.

A number of alterations have been identified in lipid metabolism within adipose tissue and liver in obesity. Less is known about the capacity of skeletal muscle for the metabolism of fatty acids in obesity-related insulin resistance, though it is evident that dry cow muscles may contain increased triglyceride content. The current study was therefore undertaken to evaluate the skeletal muscle expression of proteins of the fatty acid metabolism in dry cows with different body condition scores (BCS). Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their BCS as optimal (3.25 ≤ BCS ≤ 3.5) and high (4.0 ≤ BCS ≤ 4.25). Blood samples collection and skeletal muscle biopsies were carried out at day 10 before calving. Blood serum was assayed for concentration of resistin using a bovine specific ELISA. Protein expression of insulin receptor beta subunit (IRß), glucose transporter 4 (GLUT4), fatty acid translocase (FAT/CD36), fatty acid transporter 1 (FATP1), carnitine palmitoyltransferase 1 (CPT1), AMP-acitvated protein kinase (AMPK) and lipin 1 were analyzed in semitendinosus muscle by immunoblot. Resistin differed non-significantly between high-BCS and optimal-BCS cows. Insulin-resistant lipid metabolism in obese cows was paralleled with increased skeletal muscle expression of lipin 1 and GLUT4, and decreased expression of IRß and FATP1. These data suggest that in obesity-related insulin resistance, metabolic capacity in dry cow skeletal muscles appears to be organized towards the synthesis of signaling intermediates rather than fatty acids oxidation and that altered fatty acid uptake does not contribute to this disposition.

Cholecalciferol ameliorates insulin signalling and insulin regulation of enzymes involved in glucose metabolism in the rat heart.

CONTEXT: The evidence on potential cross-talk of vitamin D and insulin in the regulation of cardiac metabolism is very scanty. OBJECTIVE: Cholecalciferol was administered to male Wistar rats for six weeks to study its effects on cardiac glucose metabolism regulation. MATERIALS AND METHODS: An expression, phosphorylation and/or subcellular localisation of insulin signalling molecules, glucose transport and metabolism key proteins were studied. RESULTS: Circulating non-esterified fatty acids (NEFA) level was lower after cholecalciferol administration. Cholecalciferol decreased cardiac insulin receptor substrate 1 Ser307 phosphorylation, while insulin-stimulated Akt Thr308 phosphorylation was increased. Cardiac 6-phosphofructo-2-kinase protein, hexokinase 2 mRNA level and insulin-stimulated glycogen synthase kinase 3ß Ser9 phosphorylation were also increased. Finally, FOXO1 transcription factor cytosolic level was reduced. CONCLUSION: Vitamin D-related improvement of insulin signalling and insulin regulation of glucose metabolism in the rat heart is accompanied by the decrease of blood NEFA level and dysregulation of cardiac FOXO1 signalling.

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-3ß 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.

Walnut Supplementation Restores the SIRT1-FoxO3a-MnSOD/Catalase Axis in the Heart, Promotes an Anti-Inflammatory Fatty Acid Profile in Plasma, and Lowers Blood Pressure on Fructose-Rich Diet.

The benefits of walnut (Juglans regia) consumption for metabolic health are known, but the molecular background underlying their putative antioxidant and anti-inflammatory/immunomodulatory effects is underexplored. We assessed that walnut supplementation (6 weeks) reverted unfavorable changes of the SIRT1/FoxO3a/MnSOD/catalase axis in the heart induced by fructose-rich diet (FRD). Intriguingly, Nox4 was increased by both FRD and walnut supplementation. FRD increased the cytosolic fraction and decreased the nuclear fraction of the uniquely elucidated ChREBP in the heart. The ChREBP nuclear fraction was decreased in control rats subjected to walnuts. In addition, walnut consumption was associated with a reduction in systolic BP in FRD and a decrease in fatty acid AA/EPA and AA/DHA ratios in plasma. In summary, the protective effect of walnut supplementation was detected in male rats following the fructose-induced decrease in antioxidative/anti-inflammatory capacity of cardiac tissue and increase in plasma predictors of low-grade inflammation. The current results provide a novel insight into the relationship between nutrients, cellular energy homeostasis, and the modulators of inflammatory/immune response in metabolic syndrome, emphasizing the heart and highlighting a track for translation into nutrition and dietary therapeutic approaches against metabolic disease.

Beneficial effect of walnuts on vascular tone is associated with Akt signalling, voltage-dependent calcium channel LTCC and ATP-sensitive potassium channel Kv1.2.

Consumption of walnuts is beneficial for cardiovascular health. To study walnut effects on proteins involved in vascular tone regulation, control and fructose-fed rats were subjected to walnut diet for 6 weeks. In contrast with increased energy intake and body mass gain, aortic protein level of L-type calcium channel alpha subunit was decreased and the level of SUR2B subunit of ATP-sensitive K + channel was increased in healthy rats subjected to walnuts, together with improved Akt phosphorylation. Upon the walnut diet in rats subjected to fructose overload, the rise in energy intake and body mass gain, was followed by an increase in blood insulin. Although SUR2B level was elevated, the level of sodium-calcium exchanger NCX1 and inducible nitric oxide synthase were reduced and increased, respectively. In summary, walnut consumption was accompanied with moderate beneficial vascular effect in healthy rats, while an effect of walnut in rats with metabolic disturbances was rather controversial.

Walnut Consumption Induces Tissue-Specific Omega-6/Omega-3 Decrease in High-Fructose-Fed Wistar Rats.

Increased dietary, blood, and tissue n-6/n-3 fatty acid ratios are associated with obesity and metabolic syndrome. Due to Westernized dietary patterns, the increasing n-6/n-3 ratio is of growing concern worldwide, and dietary strategies aimed at its lowering are of public health importance. Walnuts are rich in dietary fats, and their consumption promotes cardiometabolic health. This study aimed to examine the effect of 6-week walnut consumption on tissue-specific n-6/n-3 ratio and fatty acid metabolic conversion in fructose-fed rats with a cluster of metabolic disorders. Male Wistar rats were fed a standard diet with or without 10% fructose in drinking water for 9 weeks. Diets of half of the animals were then supplemented with walnuts (2.4 g/day) for 6 weeks, upon which fatty acid profiles were determined in plasma, liver, adipose tissue, and kidney total lipids. Results showed that walnuts induced significant decreases in the n-6/n-3 content of total lipid pool in plasma and examined tissues, irrespective of metabolic burden. Walnut intervention decreased plasma and liver palmitoleic/palmitic, arachidonic/linoleic, and docosahexaenoic/α-linolenic acid ratios. It also modulated individual fatty acid levels by reducing arachidonic and palmitic acid and increasing α-linolenic, eicosapentaenoic, and docosapentaenoic acid in plasma and most tissues. Our study demonstrated that 6-week consumption of walnuts favorably modulated n-6/n-3 plasma and tissue ratio in male Wistar rats regardless of high-fructose feeding, underscoring the promising potential of walnuts in both prevention and treatment of the metabolic syndrome.

Effects of a fructose-rich diet and chronic stress on insulin signaling and regulation of glycogen synthase kinase-3 beta and the sodium-potassium pump in the hearts of male rats.

Both a diet rich in fructose and chronic stress exposure induce metabolic and cardiovascular disturbances. The aim of this study was to examine the effects of the fructose-rich diet and chronic stress, separately and in combination, on insulin signaling and molecules regulating glycogen synthesis and ion transport in the heart, and to reveal whether these effects coincide with changes in glucocorticoid receptor (GR) activation. Male Wistar rats were subjected to 10% fructose in drinking water and/or to chronic unpredictable stress for 9 weeks. Protein expression and/or phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B, insulin receptor substrate 1 (IRS1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase-3ß (GSK-3ß) and Na+/K+-ATPase α-subunits in cardiac tissue were analyzed by western blot. GR distribution between cytosolic and nuclear fractions was also analyzed. The fructose-rich diet decreased the level of pERK1/2 (Thr202/Tyr204) and pGSK-3ß (Ser9) independently of stress, while chronic stress increased the IRS1 content and prevented the fructose diet-induced decrease of the pAkt (Ser473) level. The fructose-rich diet in combination with chronic stress reduced the protein content of cardiac IR and attenuated IRS1 upregulation. Separate treatments increased the protein content of Na+/K+-ATPase α1- and α2-subunits, while after combined treatment the α2 content was at the control level and the α1 content was lower than the control level. The effect of combined treatment on cardiac IR and α2-subunit expression could be mediated by increased GR nuclear accumulation. Our study provides new insights into the effects of chronic stress and a combination of the fructose diet and chronic stress on the studied molecules in the heart.

Low-intensity exercise in the prevention of cardiac insulin resistance-related inflammation and disturbances in NOS and MMP-9 regulation in fructose-fed ovariectomized rats.

Exercise is important nonpharmacological treatment for improvement of insulin sensitivity in menopause. However, its effect on menopausal cardiac insulin resistance is needing further research. We investigated protective effects of low-intensity exercise on cardiac insulin signaling, inflammation, regulation of nitric oxide synthase (NOS) and matrix metalloproteinase 9 (MMP-9) in ovariectomized (OVX) Wistar rats, submitted to 10% fructose solution for 9 weeks. OVX rats were divided into control, sedentary fructose, and exercise fructose groups. Measurements of physical and biochemical characteristics were carried out to evaluate metabolic syndrome development. Messenger RNA and protein levels and phosphorylation of cardiac insulin signaling molecules, endothelial and inducible NOS (eNOS and iNOS), p65 subunit of nuclear factor κB (NFκB), tumor necrosis factor α (TNF-α), suppressor of cytokine signaling 3 (SOCS3), and MMP-9 were analyzed. Fructose increased insulin level, homeostasis model assessment (HOMA) index, and visceral adipose tissue weight, while low-intensity exercise prevented insulin level and HOMA index increase. Fructose also decreased cardiac pAkt (Ser473), peNOS (Ser1177) and increased insulin receptor substrate 1 (IRS1) phosphorylation at Ser307, pNFκB (Ser276) and NFκB and MMP-9 content, without any effect on iNOS, protein-tyrosine phosphatase 1B, TNF-α, and SOCS3. Exercise prevented changes in pIRS1 (Ser307), pAkt (Ser473), peNOS (Ser1177), pNFκB (Ser276), and NFκB expression. In addition, exercise increased pIRS1 (Tyr632), pAkt (Thr308), and eNOS expression. Low-intensity exercise prevented cardiac insulin signaling disarrangement in fructose-fed OVX rats and therefore eNOS dysfunction, as well as pro-inflammatory signaling activation, without effect on tissue remodeling, suggesting physical training as a way to reduce cardiovascular risk.

Fructose-rich diet differently affects angiotensin II receptor content in the nucleus and a plasma membrane fraction of visceral adipose tissue.

The adipose tissue renin-angiotensin system (RAS) is proposed to be a pathophysiological link between adipose tissue dysregulation and metabolic disorders induced by a fructose-rich diet (FRD). RAS can act intracellularly. We hypothesized that adipocyte nuclear membranes possess angiotensin receptor types 1 and 2 (AT1R and AT2R), which couple to nuclear signaling pathways and regulate oxidative gene expression under FRD conditions. We analyzed the effect of consumption of 10% fructose solution for 9 weeks on biochemical parameters, adipocyte morphology, and expression of AT1R, AT2R, AT1R-associated protein (ATRAP), NADPH oxidase 4 (NOX4), matrix metalloproteinase-9 (MMP-9), and manganese superoxide dismutase (MnSOD) in adipose tissue of Wistar rats. We detected AT1R and AT2R in the nuclear fraction. FRD reduced the level of angiotensin receptors in the nucleus, while increased AT1R and decreased AT2R levels were observed in the plasma membrane. FRD increased the ATRAP mRNA level and decreased MnSOD mRNA and protein levels. No significant differences were observed for MMP-9 and NOX4 mRNA levels. These findings coincided with hyperleptinemia, elevated blood pressure and triglycerides, and unchanged visceral adipose tissue mass and morphology in FRD rats. Besides providing evidence for nuclear localization of angiotensin receptors in visceral adipose tissue, this study demonstrates the different effects of FRD on AT1R expression in different cellular compartments. Elevated blood pressure and decreased antioxidant capacity in visceral fat of fructose-fed rats were accompanied by an increased AT1R level in the plasma membrane, while upregulation of ATRAP and a decrease of nuclear membrane AT1R suggest an increased capacity for attenuation of excessive AT1R signaling and visceral adiposity.

Fructose-rich diet and insulin action in female rat heart: Estradiol friend or foe?

Increased intake of fructose in humans and laboratory animals is demonstrated to be a risk factor for development of metabolic disorders (insulin resistance, metabolic syndrome, type 2 diabetes) and cardiovascular diseases. On the other hand, estradiol is emphasized as a cardioprotective agent. The main goal of this review is to summarize recent findings on damaging cardiac effects of fructose-rich diet in females, mostly experimental animals, and to evaluate protective capacity of estradiol. Published results of our and other research groups indicate mostly detrimental effects of fructose-rich diet on cardiac insulin signaling molecules, glucose and fatty acid metabolism, nitric oxide production and ion transport, as well as renin-angiotensin system and inflammation. Some of these processes are involved in cardiac insulin signal transmission, others are regulated by insulin or have an influence on insulin action. Administration of estradiol to ovariectomized female rats, exposed to increased intake of fructose, was mostly beneficial to the heart, but sometimes it was ineffective or even detrimental, depending on the particular processes. We believe that these data, carefully translated to human population, could be useful for clinicians dealing with postmenopausal women susceptible to metabolic diseases and hormone replacement therapy.

Obesity- and age-related alterations in FAT/CD36 translocation and lipin-1 subcellular localization in skeletal muscle of the Zucker rats.

Fatty acid (FA) uptake and/or intramuscular triglyceride (TG) accumulation in skeletal muscle are increased in obesity, type 2 diabetes and aging. FA translocase (FAT/CD36) translocation, lipin-1 subcellular localization and nuclear factor kappa B (NF-κB) p65 protein content in quadriceps muscle of young and old obese Zucker fa/fa rats and their lean controls were analyzed by immunoblot to define obesity- and aging-related alterations in FA uptake, their subsequent metabolic fate and potential to activate pro-inflammatory signaling. As expected, obesity increased FAT/CD36 content in plasma membrane in quadriceps muscle of fa/fa rats. Aging increased cytosolic lipin-1 content in both, obese rats and their lean controls. Also, old obese rats had decreased level of nuclear extract lipin-1compared to that in old lean rats. Neither obesity nor age altered NF-κB p65 protein content in cytosol and nuclear extract of quadriceps muscle suggesting that obesity/aging-induced changes in FA handling are not accompanied by NF-κB-mediated inflammation. Increase in plasma membrane FAT/CD36 content in obese rats and failure in lipin-1 export to nucleus with progression of obesity, implying an increase in FA uptake and their different channeling into lipid intermediates synthesis pathway in old fa/fa rats versus FA usage in lean rats of the same age.

Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves.

The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin ß-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.

Obesity-driven prepartal hepatic lipid accumulation in dairy cows is associated with increased CD36 and SREBP-1 expression.

We investigated the hypothesis that obesity in dairy cows enhanced expression of proteins involved in hepatic fatty acid uptake and metabolism. Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their body condition score (BCS) as optimal (3.25≤BCS≤3.5) and high (4.0≤BCS≤4.25). Intravenous glucose tolerance test (GTT) and liver biopsies were carried out at day 10 before calving. Blood samples were collected before (basal) and after glucose infusion, and glucose, insulin and non-esterified fatty acid (NEFA) levels were determined at each sample point. In addition, ß-hydroxybutyrate and triglycerides levels were measured in the basal samples. The liver biopsies were analyzed for total lipid content and protein expression of insulin receptor beta (IRß), fatty acid translocase (FAT/CD36) and sterol regulatory element-binding protein-1 (SREBP-1). Basal glucose and insulin were higher in high-BCS cows, which coincided with higher circulating triglycerides and hepatic lipid content. Clearance rate and AUC for NEFA during GTT were higher in optimal-BCS cows. The development of insulin resistance and fatty liver in obese cows was paralleled by increased hepatic expression of the IRß, CD36 and SREBP-1. These results suggest that increased expression of hepatic CD36 and SREBP-1 is relevant in the obesity-driven lipid accumulation in the liver of dairy cows during late gestation.