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.
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.
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
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.
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 (
= 0.0422,
= 0.000045,
= 0.00958, respectively). In addition, Lipin1, FOXO1, and SIRT1 were increased in nuclear extract after exercise compared with the control group (
= 0.000043,
= 0.0417,
= 0.0329, respectively). In cardiac lysate, low-intensity exercise caused significantly increased protein level of PPARα, PGC1, FOXO1, and SIRT1 compared with control (
= 0.0377,
= 0.0275,
= 0.0096,
= 0.0282, respectively) and PGC1 level compared with the fructose group (
= 0.0417).
The obtained results imply that the heart with a metabolic burden additionally relies on FA as an energy substrate after low-intensity running.
The study aimed to determine the concentration of energy-related hormones in cow’s milk and to consider them from a public health perspective. Fourteen Holstein cows were subjected to milk and blood ...sampling on the following days in lactation (DIL): 10, 30, 60, 90, 150, 180, 210, 250 and 280 to determine milk hormones, fat and protein content and blood biochemical parameters. For the same purpose, bulk-tank milk was sampled and samples of retail m ilk with 1.5% (CM
) and 3.2% (CM
) fat was purchased. Milk insulin-like growth factor-1 (IGF-1) values were significantly lower at 90, 150, 180, 210 and 250 and significantly higher at 10, 30 and 60 DIL than lactation average (LA). Milk insulin concentrations were significantly lower at 30, 60 and 90 and higher at 210, 250 and 280 DIL than LA. Free thyroxine (fT
) level in the milk was higher at 250 DIL, while milk free triiodothyronine (fT
) concentrations were lower at 30, 60, 90 and 280 DIL, and significantly higher at 10 and 180 DIL than respective LA. Milk cortisol levels were lower at 60 and 280 DIL than LA. All measured milk hormones were significantly lower in CM
compared to CM
, bulk-tank milk and LA. An exception was the LA of IGF-1, which was significantly lower than the IGF-1 content in CM
. Blood biochemical parameters fluctuated evenly during lactation and were within the reference range. Hormone concentrations in cow’s milk fluctuate during lactation, giving milk an important role in the context of public health.
Excessive fructose consumption causes ectopic lipid storage leading to metabolic disorders and cardiovascular diseases associated with defective substrate utilisation in the heart.
Examining the ...preventive impact of low-intensity exercise on alterations related to fructose-rich diet (FRD) on cardiac fatty acid (FA) transport and metabolism.
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.
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.
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.
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.
Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined ...the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet.
•The protective role of exercise against cardiac insulin resistance is proposed.•Fructose diet disturbs cardiac insulin signaling.•Exercise decreased visceral adiposity and increased insulin sensitivity.•Exercise prevented most of insulin signaling disturbances caused by fructose diet.•Consequently exercise restored function of endothelial nitric oxide synthase.
Fructose rich diet increases hepatic triglycerides production and has deleterious cardiac effects. Estrogens are involved in regulation of lipid metabolism as well, but their effects are cardio ...beneficial. In order to study effects of fructose rich diet on the main heart fatty acid transporter CD36 and the role of estrogens, we subjected ovariectomized female rats to the standard diet or fructose rich diet, with or without estradiol (E2) replacement. The following parameters were analyzed: feeding behavior, visceral adipose tissue mass, plasma lipids, cardiac CD36 expression, localization and insulin regulation, as well as the profile of cardiac lipids. Results show that fructose rich diet significantly increased plasma triglycerides and decreased plasma free fatty acid (FFA) concentration, while E2 additionally emphasized FFA decrease. The fructose diet increased cardiac plasma membrane content of CD36 in the basal and insulin-stimulated states, and decreased its low density microsomes content. The E2 in fructose-fed rats raised the total cardiac protein content of CD36, its presence in plasma membranes and low density microsomes, and cardiac deposition of triglycerides, as well. Although E2 counteracts fructose in some aspects of lipid metabolism, and separately they have opposite cardiac effects, in combination with fructose rich diet, E2 additionally enhances CD36 presence in plasma membranes of cardiac cells and triglycerides accumulation, which paradoxically might promote deleterious effects of fructose diet on cardiac lipid metabolism. Taken together, the results presented in this work are of high importance for clinical administration of estrogens in females with a history of type 2 diabetes.
Polycystic ovary syndrome (PCOS) is associated with an altered plasma lipid profile and increased risk for cardiovascular diseases. We hypothesized that molecular mechanisms underlying cardiac ...pathology in PCOS involve changes in expression and subcellular localization of several key proteins involved in cardiac lipid transport and metabolism, such as fatty acid transporter CD36, lipin 1, peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1 (PGC1), and carnitine palmitoyltransferase 1 (CPT1). We used the animal model of PCOS obtained by treating female rats with dihydrotestosterone (DHT). Protein levels of CD36, lipin 1, PPARα, PGC1, and antioxidative enzymes were assessed by Western blot in different cardiac cell compartments. Cardiac triglycerides (TG) and lipid peroxidation were also measured. The content of CD36 was decreased in both the cardiac plasma membranes and intracellular pool. On the other hand, total content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast to decreased microsomal lipin 1 content. An increase in nuclear content of lipin 1 was observed together with elevation of nuclear PPARα and PGC1, and an increase in CPT1 expression. However, lipid peroxidation was reduced in the heart, without alterations in antioxidative enzymes expression and cardiac TG content. The results indicate that treatment of female rats with DHT is accompanied by a decrease of fatty acid uptake and a reduction of lipid peroxidation in the heart. The observed elevation of lipin 1, PPARα, PGC1, and CPT1 expression suggests that cardiac fatty acid metabolism is shifted toward mitochondrial beta oxidation.
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