Dietary Salvia hispanica L. reduces cardiac oxidative stress of dyslipidemic insulin-resistant rats.

Salvia hispanica L., commonly known as chia seed, has beneficial effects upon some signs of metabolic syndrome (MS), such as dyslipidemia and insulin resistance. However, its action on cardiac oxidative stress associated with MS remains unknown. The goal of this study was to analyze the possible beneficial effects of chia seed (variety Salba) upon the oxidative stress of left ventricle heart muscle (LV) of a well-established dyslipidemic insulin-resistant rat model induced by feeding them a sucrose-rich diet (SRD). Male Wistar rats received an SRD for 3 months. After that, for 3 additional months, half of the animals continued with the SRD, while the other half received the SRD containing chia as the source of dietary fat instead corn oil (SRD+chia). In the LV of SRD-fed rats, chia seed improved/reverted the depleted activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase, and ameliorated manganese superoxide dismutase messenger RNA (mRNA) levels increasing the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2). Improved the glutathione redox estate, reactive oxygen species, and thiobarbituric acid reactive substances contents normalizing the p47NOX subunit mRNA level. Furthermore, chia normalized hypertension and plasma levels of pro-inflammatory cytokines and oxidative stress biomarkers. The findings show that chia seed intake impacts positively upon oxidative imbalance of LV of dyslipidemic insulin-resistant rats. Novelty Healthy effects of chia seed involve an improvement of cardiac antioxidant defenses through Nrf2 induction. Chia seed intake reduces cardiac oxidative stress markers of dyslipidemic insulin-resistant rats. Dietary chia seed restores cardiac unbalanced redox state of dyslipidemic insulin-resistant rats.

Dietary fish oil ameliorates adipose tissue dysfunction in insulin-resistant rats fed a sucrose-rich diet improving oxidative stress, peroxisome proliferator-activated receptor γ and uncoupling protein 2.

This work aims to assess the possible beneficial effects of dietary fish oil (FO) on the pre-existing adipose tissue dysfunction through the improvement or reversion of the mechanisms underlying oxidative stress and pro-inflammatory cytokines in dyslipemic insulin-resistant rats. Wistar rats were fed a sucrose rich diet (SRD) for 6 months. After that half of the animals continued with the SRD until month 8 while in the other half corn oil was replaced by FO for 2 months (SRD + FO). A reference group consumed a control diet all the time. In an epididymal fat pad, we analyzed antioxidant and oxidant enzyme activities, ROS content, glutathione redox state, the protein level of peroxisome proliferator-activated receptor gamma (PPARγ) and the expression and protein levels of uncoupling protein 2 (UCP2) as well as oxidative stress biomarkers and TNF-α and IL-6 plasma levels. Besides these, insulin sensitivity and the composition of fatty acid phospholipids of adipose tissue were measured. Compared with the SRD the SRD + FO fed group showed a decrease of fat pad weight and the antioxidant and oxidant enzyme activities and ROS content returned to control values along with normal plasma TNF-α and IL-6 levels. FO normalized both the decrease of PPARγ protein and the increase of protein and expression of UCP2. Furthermore, FO increased the n-3/n-6 fatty acid ratio in the adipose tissue phospholipids and normalized dyslipidemia and insulin resistance. Finally, these findings reinforce the view that dietary FO may exert a beneficial effect in ameliorating the dyslipidemia and insulin resistance in this animal model.

Dietary soya protein improves intra-myocardial lipid deposition and altered glucose metabolism in a hypertensive, dyslipidaemic, insulin-resistant rat model.

This study investigates the effects of replacing dietary casein by soya protein on the underlying mechanisms involved in the impaired metabolic fate of glucose and lipid metabolisms in the heart of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). To test this hypothesis, Wistar rats were fed an SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed an SRD in which casein was substituted by soya. The control group received a diet with maize starch as the carbohydrate source. Compared with the SRD-fed group, the following results were obtained. First, soya protein significantly (P<0·001) reduced the plasma NEFA levels and normalised dyslipidaemia and glucose homoeostasis, improving insulin resistance. The protein levels of fatty acid translocase at basal state and under insulin stimulation and the protein levels and activity of muscle-type carnitine palmitoyltransferase 1 were normalised. Second, a significant (P<0·001) reduction of TAG, long-chain acyl CoA and diacylglycerol levels was observed in the heart muscle. Third, soya protein significantly increased (P<0·01) GLUT4 protein level under insulin stimulation and normalised glucose phosphorylation and oxidation. A reduction of phosphorylated AMP protein kinase protein level was recorded without changes in uncoupling protein 2 and PPARα. Fourth, hydroxyproline concentration decreased in the left ventricle and hypertension was normalised. The new information provided shows the beneficial effects of soya protein upon the altered pathways of glucose and lipid metabolism in the heart muscle of this rat model.

Effects of post-suckling n-3 polyunsaturated fatty acids: prevention of dyslipidemia and liver steatosis induced in rats by a sucrose-rich diet during pre- and post-natal life.

The interaction between fetal programming and the post-natal environment suggests that the post-natal diet could amplify or attenuate programmed outcomes. We investigated whether dietary n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) at weaning resulted in an amelioration of dyslipidemia, adiposity and liver steatosis that was induced by a sucrose-rich diet (SRD; where the fat source is corn oil) from the onset of pregnancy up to adulthood. During pregnancy and lactation, dams were fed an SRD or the standard powdered rodent commercial diet (RD). At weaning and until 150 days of life, male offspring from SRD-dams were divided into two groups and fed an SRD or SRD-with-fish oil [where 6% of the corn oil was partially replaced by fish oil (FO) 5% and corn oil (CO) 1%], forming SRD-SRD or SRD-FO groups. Male offspring from RD-dams continued with RD up to the end of the experimental period, forming an RD-RD group. The presence of FO in the weaning diet showed the following: prevention of hypertriglyceridemia and liver steatosis, together with increased lipogenic enzyme activity caused by a maternal SRD; the complete normalization of CPT I activity and PPARα protein mass levels; a slight but not statistically significant accretion of visceral adiposity; and limited body fat content and reduced plasma free fatty acid levels. All of these results were observed even in the presence of a high-sucrose diet challenge after weaning. SRD-dams' breast milk showed a more saturated fatty acid composition. These results suggest the capacity of n-3 PUFAs to overcome some adverse outcomes induced by a maternal and post-weaning sucrose-rich diet.

Time course of adipose tissue dysfunction associated with antioxidant defense, inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats.

The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated following the time course of the development of oxidative stress, changes in proinflammatory cytokines and adiponectin levels, and their relationship with insulin resistance. We analyzed the morphometric characteristics of epididymal adipocytes, de novo lipogenesis enzyme activities and cellular antioxidant defense, inflammatory mediators, adiponectin levels and insulin resistance in rats fed a sucrose-rich diet for 3, 15 or 30 weeks and compared to those fed a control diet. The results showed a depletion of antioxidant enzyme activities in the fat pads of rats fed a sucrose-rich diet, with an increase in xanthine oxidase activity and lipid peroxidation after 3, 15 and 30 weeks on the diet. Superoxide dismutase activity and the redox state of glutathione showed a significant decrease at weeks 15 and 30. This was accompanied by visceral adiposity and enhanced lipogenic enzyme activities. An increase in the plasma levels of proinflammatory markers (TNF-α and IL-6) was recorded only after 30 weeks on the diet. A reduction in plasma adiponectin levels accompanied the time course of deterioration of whole-body insulin sensitivity. The results suggest that lipid peroxidation, depletion of antioxidant defenses and changes in inflammatory cytokines induced by a sucrose-rich diet contribute to the dysregulation of adipose tissue and insulin resistance. Finally, these results show that the progressive deterioration of adipose tissue function, which begins in the absence of both visceral adiposity and overweight, is highly dependent on the length of time on the diet.

Maternal sucrose-rich diet and fetal programming: changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis in adult offspring.

Nutritional insults during pregnancy and lactation (P + L) are often associated with offspring health risks. We investigated the effect of maternal exposure to a sucrose-rich diet (SRD) during P + L on glucose and lipid metabolism of adult offspring regardless of post-weaning diet. Dams were fed an SRD or a control diet (CD) during P + L. After weaning, male offspring from SRD and CD dams were divided into two groups and fed a CD or SRD until 150 days old forming CD-CD, CD-SRD, SRD-SRD and SRD-CD groups. Offspring where SRD was fed at any period of life showed: (1) increased adipose tissue weight without changes in the final body weight; (2) dyslipidemia as a result of increased very low density lipoprotein triglyceride secretion rate and decreased triglyceride clearance; (3) hepatic steatosis associated with increased activity of key enzymes involved in liver de novo lipogenesis and significant decrease of the activity of mitochondrial fatty acid oxidation enzyme. These results were more pronounced in CD-SRD and SRD-SRD groups. (4) Hyperglycemia without changes in insulin levels, plus a deterioration of intravenous glucose tolerance and intraperitoneal insulin tolerance test. We hypothesized that SRD during P + L could be associated with a programming effect on glucose homeostasis and hepatic lipid metabolism that predispose offspring to develop later-life insulin resistance and metabolic disorders, regardless of post-natal diet.

Changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis induced by an acetyl-L-carnitine and nicotinamide treatment in dyslipidaemic insulin-resistant rats.

Normal rats fed a sucrose-rich diet (SRD) develop dyslipidaemia and insulin resistance. The present study examined whether administration of the mitochondrial nutrients nicotinamide and acetyl-L-carnitine reversed or improved these metabolic abnormalities. Male Wistar rats were fed an SRD for 90 days. Half the rats then received daily injections of nicotinamide (25 mg/kg, i.p.) and acetyl-L-carnitine (50 mg/kg, i.p.) for a further 90 days. The remaining rats in the SRD-fed group and those in a normal chow-fed control group were injected with an equal volume of saline solution for the same period. The following parameters were determined in all groups: (i) liver activity of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and carnitine-palmitoyl transferase-1 (CPT-1); (ii) hepatic and skeletal muscle triacylglycerol content, plasma glucose, insulin, free fatty acid (FFA) and triacylglycerol levels and pancreatic insulin content; and (iii) glucose tolerance. Administration of nicotinamide and acetyl-L-carnitine to the SRD-fed rats reduced dyslipidaemia, liver steatosis, muscle triacylglycerol content and hepatic FAS and ACC activities and increased CPT-1 activity. In addition nicotinamide and acetyl-L-carnitine improved the glucose disappearance rate (K(g)), normalized plasma glucose levels and moderately increased insulinaemia without altering pancreatic insulin content. Finally, nicotinamide and acetyl-l-carnitine administration reduced bodyweight gain and visceral adiposity. The results of the present study suggest that altering key hepatic lipogenic and fatty acid oxidative enzymatic activity could improve dyslipidaemia, liver steatosis and visceral adiposity. Indeed, administration of nicotinamide and acetyl-l-carnitine improved glucose intolerance and normalized plasma glucose levels.

Dietary chia seed induced changes in hepatic transcription factors and their target lipogenic and oxidative enzyme activities in dyslipidaemic insulin-resistant rats.

The present study analyses the effect of dietary chia seed rich in n-3 α-linolenic acid on the mechanisms underlying dyslipidaemia and liver steatosis developed in rats fed a sucrose-rich diet (SRD) for either 3 weeks or 5 months. The key hepatic enzyme activities such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), glucose-6-phosphate dehydrogenase (G-6-PDH), carnitine palmitoyltransferase-1 (CPT-1) and fatty acid oxidase (FAO) involved in lipid metabolism and the protein mass levels of sterol regulatory element-binding protein-1 (SREBP-1) and PPARα were studied. (1) For 3 weeks, Wistar rats were fed either a SRD with 11 % of maize oil (MO) as dietary fat or a SRD in which chia seed replaced MO (SRD+Chia). (2) A second group of rats were fed a SRD for 3 months. Afterwards, half the rats continued with the SRD while for the other half, MO was replaced by chia for 2 months (SRD+Chia). In a control group, maize starch replaced sucrose. Liver TAG and the aforementioned parameters were analysed in all groups. The replacement of MO by chia in the SRD prevented (3 weeks) or improved/normalised (5 months) increases in dyslipidaemia, liver TAG, FAS, ACC and G-6-PDH activities, and increased FAO and CPT-1 activities. Protein levels of PPARα increased, and the increased mature form of SREBP-1 protein levels in the SRD was normalised by chia in both protocols (1 and 2). The present study provides new data regarding some key mechanisms related to the fate of hepatic fatty acid metabolism that seem to be involved in the effect of dietary chia seed in preventing and normalising/improving dyslipidaemia and liver steatosis in an insulin-resistant rat model.

Fish oil reverses the altered glucose transporter, phosphorylation, insulin receptor substrate-1 protein level and lipid contents in the skeletal muscle of sucrose-rich diet fed rats.

The role and underlying mechanisms by which n-3 polyunsaturated fatty acids (PUFA) prevent/reverse SRD-induced insulin resistance (IR) in the muscle are not completely understood. Therefore, we examined: triglyceride, diacylglycerol, PKCθ, Glut-4, enzymatic hexokinase activity, IRS-1 protein mass level, and fatty acid composition of muscle phospholipids. Rats were fed a SRD during 6 months. Thereafter, half the animals continued with SRD up to 8 months; the other half was fed a SRD in which CO (8% wt/wt) was replaced by FO (7%+1% CO) for 2 months. Results were compared with those obtained in rats fed a control diet (CD). In SRD-fed rats, FO oil normalized/improved lipid storage and PKCθ protein mass level. Effects of insulin were comparable with those of CD-fed rats. FO reversed impaired glucose phosphorylation, IRS-1, and, under insulin stimulation, Glut-4 protein mass level. FO normalized insulin resistance and increased n-3 PUFAs in muscle phospholipids.

Sucrose-rich feeding during rat pregnancy-lactation and/or after weaning alters glucose and lipid metabolism in adult offspring.

1. Adverse fetal and early life environments predispose to the development of metabolic disorders in adulthood. The present study examined whether offspring of normal Wistar dams fed a high-sucrose diet (SRD) developed impaired lipid and glucose homeostasis when fed a control diet (CD) after weaning. In addition, we investigated whether there were more pronounced derangements in lipid and glucose homeostasis when offspring of SRD-fed Wistar were fed an SRD after weaning compared with those in offspring of CD-fed dams weaned on an SRD. 2. During pregnancy and lactation, female rats were fed either an SRD or CD. After weaning, half the male offspring from both groups were fed a CD or SRD, up to 100 days of age (CD-CD, CD-SRD, SRD-SRD and SRD-CD groups). 3. Final bodyweight was similar between all groups, although offspring of SRD-fed dams had lighter bodyweight at birth. Plasma lipid and glucose levels were significantly higher (P < 0.05) without changes in insulin levels in the CD-SRD, SRD-SRD and SRD-CD groups compared with the CD-CD group. Dyslipidaemia in the CD-SRD and SRD-SRD groups resulted from increased secretion of very low-density lipoprotein triacylglycerol, as well as decreased triacylglycerol (TAG) clearance that was associated with increased liver TAG content (P < 0.05) compared with the CD-CD group. The hypertriglyceridaemia observed in the SRD-CD group was mostly associated with decreased TAG clearance. Altered glucose and insulin tolerance were observed when the SRD was fed during any period of life. 4. These data support the hypothesis that early life exposure to SRD is associated with changes in lipid and glucose metabolism, leading to an unfavourable profile in adulthood, regardless of whether offspring consumed an SRD after weaning.

Fish oil normalizes plasma glucose levels and improves liver carbohydrate metabolism in rats fed a sucrose-rich diet.

A sucrose-rich diet (SRD) induces insulin resistance and dyslipidemia with impaired hepatic glucose production and gluconeogenesis, accompanied by altered post-receptor insulin signaling steps. The aim of this study was to examine the effectiveness of fish oil (FO) to reverse or improve the impaired hepatic glucose metabolism once installed in rats fed 8 months a SRD. In the liver of rats fed SRD in which FO replaced corn-oil during the last 2 months, as dietary fat, several key enzyme activities and metabolites involved in glucose metabolisms (phosphorylation, glycolysis, gluconeogenesis and oxidative and non oxidative glucose pathway) were measured. The protein mass levels of IRS-1 and αp85 PI-3K at basal conditions were also analyzed. FO improved the altered activities of some enzymes involved in the glycolytic and oxidative pathways observed in the liver of SRD fed rats but was unable to restore the impaired capacity of glucose phosphorylation. Moreover, FO reversed the increase in PEPCK and G-6-Pase and reduced the G-6-Pase/GK ratio. Glycogen concentration and GSa activity returned to levels similar to those observed in the liver of the control-fed rats. Besides, FO did not modify the altered protein mass levels of IRS-1 and αp85 PI-3K. Finally, dietary FO was effective in reversing or improving the impaired activities of several key enzymes of hepatic carbohydrate metabolism contributing, at least in part, to the normalization of plasma glucose levels in the SRD-fed rats. However, these positive effects of FO were not observed under basal conditions in the early steps of insulin signaling transduction.

Soya protein ameliorates the metabolic abnormalities of dysfunctional adipose tissue of dyslipidaemic rats fed a sucrose-rich diet.

The present study investigates whether the replacement of dietary casein by soya protein isolate could be able to improve and/or even revert the morphological and metabolic abnormalities underlying the adipose tissue dysfunction of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). For this purpose, Wistar rats were fed a SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed a SRD in which the source of protein, casein, was substituted by soya. The control group received a diet in which the source of carbohydrate was maize starch. Compared with the SRD-fed group, the results showed that: (1) soya protein decreased body-weight gain, limited the accretion of visceral adiposity and decreased adipose tissue cell volume without changes in total cell number; (2) soya protein increased the protein mass expression of PPARγ, which was significantly reduced in the fat pad of the SRD-fed rats; (3) the activity of the enzymes involved in the de novo lipogenesis of adipose tissue was significantly decreased/normalised; (4) soya protein corrected the inhibitory effect of SRD upon the anti-lipolytic action of insulin, reduced basal lipolysis and normalised the protein mass expression of GLUT-4. Dyslipidaemia, glucose homeostasis and plasma leptin levels returned to control values. The present study provides data showing the beneficial effects of soya protein to improve and/or revert the adipose tissue dysfunction of a dyslipidaemic insulin-resistant rat model and suggests that soya could maintain the functionality of the adipose tissue-liver axis improving/reverting lipotoxicity.

Is Lipotoxicity presents in the early stages of an experimental model of autoimmune diabetes? Further studies in the multiple low dose of streptozotocin model.

An increased availability of plasma free fatty acids (FFA) seems to play a role in the early stages of experimental type 1 diabetes mellitus induced in C57BL/6J mice by multiple low doses of streptozotoxin (mld-STZ). We analyzed the temporal changes of: (1) plasma and skeletal muscle lipids and their relationship with glucose metabolism; (2) triglyceride (Tg) concentration in isolated islets; (3) intraperitoneal glucose tolerance test; and (4) insulin secretion patterns when the three mutually interactive glucose signaling pathways were activated. Animals were killed by cervical dislocation at days 4, 6, 7, 8, 9 and 12 post first injection of mld-STZ. Compared with control mice, we observed: (1) at day 6, a significant increase of plasma FFA and both muscle and islet Tg content and a significant decrease of muscle pyruvate dehydrogenase activity. These parameters further deteriorated with time. (2) plasma Tg, glucose and insulin levels and glucose tolerance test were significantly different only after day 8. (3) an increase in both phases of the glucose plus palmitate-stimulated insulin secretion was observed at day 4. This effect progressively decreased since day 7 up to day 9. Moreover, an inhibitory action of cerulenin over glucose plus palmitate-stimulated insulin secretion was observed between days 6 and 9. Taken together these results suggest that early alteration in carbohydrate and lipid metabolism could represent a "metabolic window" which would develop between days 6 and 8. Afterwards, subsequent immunological alterations, apoptosis and necrosis induced the destruction of ß cells and would mask the results mentioned above.

ß-Cell adaptation/dysfunction in an animal model of dyslipidemia and insulin resistance induced by the chronic administration of a sucrose-rich diet.

Glucose stimulated insulin secretion (GSIS) was different in rats chronically fed a sucrose-rich diet (SRD) for 3 or 30 wk. This work proposes possible mechanisms underlying insulin secretion changes from ß-cell throughout these feeding periods. In isolated islets of rats fed the SRD or a control diet (CD) we examined: 1- the glucokinase and hexokinase activities and their protein mass expression; 2- pyruvate dehydrogenase activity; 3- uncoupling protein 2 (UCP2) and peroxisome proliferators-activated receptor γ (PPAR γ) protein mass expression. At 3 wk on diet the SRD-fed rats showed: a marked increase in the first peak of GSIS; increased glucokinase protein mass expression without changes in glucokinase and hexokinase activities; increased PPARγ protein mass expression without changes in the UCP2 protein mass expression. No changes in either glucose oxidation and triglyceride content within the ß-cell were observed. After 30 wk of feeding, a significant decrease of both glucokinase activity and its protein mass expression was accompanied by altered glucose oxidation, a triglyceride increase within the ß-cell and a significant increase of PPARγ and UCP2 protein mass expression. Moreover GSIS depicted an absence of the first peak with an increase in the second phase. Finally, the SRD chronic administration altered GSIS by different mechanisms depending on the time on diet. At an early stage, the increased protein mass expression of the glucokinase and a fatty acid cooperative effect inducing PPARγ expression seem to be the mechanisms involved. At a late stage, glucolipotoxicity appears to be the cellular mechanism contributing to progressive ß-cell dysfunction.

Nuclear receptors and hepatic lipidogenic enzyme response to a dyslipidemic sucrose-rich diet and its reversal by fish oil n-3 polyunsaturated fatty acids.

A sucrose-rich diet (SRD), compared with a starch diet, induces time-dependent metabolic disorders and insulin resistance with hypertriglyceridemia, similar to type 2 diabetes. In this study, we examined the effect of SRD, after 8 mo, on nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha), and liver X receptor-alpha (LXRalpha), stearoyl-CoA desaturase-1 (SCD-1), and Delta6 and Delta5 desaturases mRNA and activity, hepatic enzymes involved in lipid metabolism, and fatty acid (FA) composition as well as the reversal produced by cod liver oil. SRD induced triglyceride increase in plasma and liver, increasing the anabolic FA synthase, malic enzyme, and glucose-6-phosphate dehydrogenase, but not the prooxidative enzymes FA oxidase and carnitine palmitoyltransferase I, and correspondingly decreased PPARalpha and increased LXRalpha expressions. Results suggest a contribution of both nuclear receptors' interaction on these enzymatic activities. SRD depressed SCD-1 without altering oleic acid proportion and increased Delta6 and Delta5 desaturases and the proportion of n-6 arachidonic acid. Therefore, the data do not support that SRD hypertriglyceridemia is produced by increased SCD-1-dependent oleic acid biosynthesis. The administration of 7% cod liver oil for 2 mo depressed LXRalpha, enhancing PPARalpha in control and SRD-fed rats, reversing the activity of the hepatic enzymes involved in lipid metabolism and therefore the hyperlipidemia produced by the SRD. Fish oil increased n-3 PUFA and depressed n-6 PUFA of liver lipids without altering the 18:1/18:0 ratio, suggesting that its effects were produced mainly by competition of dietary n-6 and n-3 FA and not through desaturase activity modification.

Lipogenic enzyme activities and glucose uptake in fat tissue of dyslipemic, insulin-resistant rats: effects of fish oil.

OBJECTIVE: The purposes of the present work were twofold: (1) investigate same mechanisms involved in the development of fat cell hypertrophy in the experimental model of dyslipidemia and whole-body insulin resistance induced in rats chronically fed a sucrose-rich diet (SRD); and (2) analyze the possible beneficial effect of fish oil on these mechanisms. METHODS: For 6 mo, male Wistar rats received a sucrose-rich diet (62.5% w/w sucrose, 8% corn oil) or a control diet in which sucrose was replaced by starch. After this period, the sucrose-fed animals were divided randomly into two groups: the first one continued with the same diet up to 8 mo and the second one received the same diet, but with corn oil replaced by 7% fish oil+1 % corn oil. Rats were fed with this diet for the next 2 mo. RESULTS: Although an enlarged fat cell lipolysis and an impaired insulin-stimulated glucose uptake were present in the fat cells of SRD-fed rats, an increase of several key enzymes of the novo lipogenesis could be one of the possible mechanisms involved in visceral adiposity. The addition of dietary fish oil restored or improved the above abnormalities. CONCLUSION: This study shows possible mechanisms conditioning the influence of nutrients on the development and management of dyslipidemia, insulin sensitivity, and fat cell accretion, all abnormalities present in the metabolic syndrome.

Increased leptin storage with altered leptin secretion from adipocytes of rats with sucrose-induced dyslipidemia and insulin resistance: effect of dietary fish oil.

This study examined the effect of long-term feeding a high-sucrose diet (SRD) on the modulation of rat adipocyte's leptin secretion and storage. For this purpose, we analyzed (a) basal and insulin-stimulated leptin release and the role of isoproterenol and palmitate on insulin-stimulated leptin secretion, (b) the correlation between leptin and glycerol released, (c) the relationship between leptin contents and adiposity, and (d) the effect of fish oil (FO) administration on the above parameters. Wistar rats were fed an SRD for 6 months. Whereas half the animals continued with SRD up to month 8, the other half was fed an SRD in which FO partially replaced corn oil from months 6 to 8. Total leptin release was reduced both basally and under insulin stimulation in SRD-fed rats. However, the ratio of leptin released after hormone stimulation to basal leptin levels was similar in the 3 dietary groups. Isoproterenol inhibited insulin-stimulated leptin release in the 3 groups, but the percentage was lower in the SRD. Palmitic acid mimicked the effect of isoproterenol. Leptin release from adipocyte of SRD-fed rats negatively correlated with glycerol release. Leptin store increased in fat pads of SRD and positively correlated with adiposity. Fish oil reduced leptin content and fat pad hypertrophy, and normalized basal lipolysis, leptinemia, and glucose homeostasis. This suggests that enhanced lipolysis and altered insulin sensitivity could play a role in the decrease of leptin released in SRD-fed rats. This is consistent with the reversion of all the alterations after FO administration.

Dietary chia seed (Salvia hispanica L.) rich in alpha-linolenic acid improves adiposity and normalises hypertriacylglycerolaemia and insulin resistance in dyslipaemic rats.

The present study investigates the benefits of the dietary intake of chia seed (Salvia hispanica L.) rich in alpha-linolenic acid and fibre upon dyslipidaemia and insulin resistance (IR), induced by intake of a sucrose-rich (62.5 %) diet (SRD). To achieve these goals two sets of experiments were designed: (i) to study the prevention of onset of dyslipidaemia and IR in Wistar rats fed during 3 weeks with a SRD in which chia seed was the dietary source of fat; (ii) to analyse the effectiveness of chia seed in improving or reversing the metabolic abnormalities described above. Rats were fed a SRD during 3 months; by the end of this period, stable dyslipidaemia and IR were present in the animals. From months 3-5, half the animals continued with the SRD and the other half were fed a SRD in which the source of fat was substituted by chia seed (SRD+chia). The control group received a diet in which sucrose was replaced by maize starch. The results showed that: (i) dietary chia seed prevented the onset of dyslipidaemia and IR in the rats fed the SRD for 3 weeks--glycaemia did not change; (ii) dyslipidaemia and IR in the long-term SRD-fed rats were normalised without changes in insulinaemia when chia seed provided the dietary fat during the last 2 months of the feeding period. Dietary chia seed reduced the visceral adiposity present in the SRD rats. The present study provides new data regarding the beneficial effect of chia seed upon lipid and glucose homeostasis in an experimental model of dislipidaemia and IR.

Soya protein reverses dyslipidaemia and the altered capacity of insulin-stimulated glucose utilization in the skeletal muscle of sucrose-rich diet-fed rats.

The present study investigates the benefits of dietary intake of soya protein upon dyslipidaemia and insulin resistance in rats chronically (8 months) fed a sucrose-rich (63 %) diet (SRD). For this purpose, we analysed the effectiveness of soya protein isolate in improving or reversing these metabolic abnormalities. Wistar rats were fed a SRD for 4 months. By the end of this period, stable dyslipidaemia and insulin resistance were present in the animals. From months 4 to 8, half the animals continued with the SRD and the other half were fed a SRD in which the source of protein casein was substituted by soya. The control group received a diet in which the source of carbohydrate was maize starch. The results showed that: (1) soya protein normalized plasma TAG, cholesterol and NEFA levels in the SRD-fed rats. Moreover, the addition of soya protein reversed the hepatic steatosis. (2) Glucose homeostasis was normalized without changes in circulating insulin levels. Whole-body peripheral insulin sensitivity substantially improved. Besides, soya protein moderately decreases body weight gain limiting the accretion of visceral fat. (3) By shifting the source of dietary protein from casein to soya during the last 4 months of the feeding period it was possible to reverse both the diminished insulin-stimulated glucose oxidation and disposal in the skeletal muscle of SRD-fed rats. This study provides new data showing the beneficial effect of soya protein upon lipid and glucose homeostasis in the experimental model of dyslipidaemia and insulin resistance.

Dietary fish oil reverses lipotoxicity, altered glucose metabolism, and nPKCepsilon translocation in the heart of dyslipemic insulin-resistant rats.

The present study analyzes several markers of energy metabolism in the heart muscle of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD, 62.5% wt/wt) for 8 months. It also explores the possible beneficial effects of dietary fish oil supplementation on cardiac lipids and glucose metabolism. With this purpose, male Wistar rats were fed an SRD for 6 months. Whereas half of the animals continued with the same diet for up to 8 months, the other half was fed an SRD in which fish oil (7% + 1% corn oil wt/wt) replaced corn oil (8% wt/wt) from months 6 to 8. The results were compared with rats fed a control diet (starch 62.5% wt/wt). The cardiac muscle of SRD-fed rats showed (1) a significant reduction (P < .05) in key enzymes activities and metabolites involved in glucose metabolism, accompanied by a significant (P < .05) increase of lipid storage (triglyceride, long-chain acyl coenzyme A, and diacylglycerol), and (2) a significant increase (P < .05) of nPKCepsilon protein mass expression in the membrane fraction without changes in the cPKCbetaII. Dietary fish oil, which reduces the availability of plasma lipid flux and normalizes glucose homeostasis, was able to reverse heart muscle lipotoxicity. Fish oil benefits key enzymes activities in glucose metabolism and normalizes glycogen and glucose-6-phosphate concentration, and the altered nPKCepsilon protein mass expression translocation in the heart of SRD-fed rats. Our findings suggest that manipulation of dietary fats may play a key role in the management of lipid disorders, offering a protection against the development of cardiovascular diseases.