Dietary fish oil reverse epididymal tissue adiposity, cell hypertrophy and insulin resistance in dyslipemic sucrose fed rat model small star, filled

The present work was designed to assess the possible benefits of (7% w/w) dietary fish oil in reversing the morphological and metabolic changes present in the adipose tissue of rats fed an SRD for a long time. With this purpose, in the epididymal fat tissue, we investigated the effect of dietary fish oil upon: i) the number, size and distribution of cells, ii) the basal and stimulated lipolysis, iii) the lipoprotein lipase (LPL) and the glucose 6-phosphate dehydrogenase activities, and iv) the antilipolytic action of insulin. The study was conducted on rats fed an SRD during 120 days with fish oil being isocaloric substituted for corn oil for 90-120 days in half the animals. Permanent hypertriglyceridemia, insulin resistance and abnormal glucose homeostasis were present in the rats before the source of fat in the diet was replaced. The major new findings of this study are the following: i) Dietary fish oil markedly reduced the fat pads mass, the hypertrophy of fat cells and improved the altered cell size distribution. ii) The presence of fish oil in the diet corrected the inhibitory effect of high sucrose diet upon the antilipolytic action of insulin, reduced the "in vitro" enhanced basal lipolysis and normalized isoproterenol-stimulated lipolysis. Fat pads lipoprotein lipase activity decreased reaching values similar to those observed in age-matched controls fed a control diet (CD). These effects were not accompanied by any change in rat body weight. All these data suggest that the dyslipemic rats fed a moderate amount of dietary fish oil constitute a useful animal model to study diet-regulated insulin action.     

Role of skeletal muscle on impaired insulin sensitivity in rats fed a sucrose-rich diet: effect of moderate levels of dietary fish oil

In the present study we investigated: (1) the contribution of the skeletal muscle to the mechanisms underlying the impaired glucose homeostasis and insulin sensitivity present in dyslipemic rats fed a sucrose-rich diet (SRD) over a long period of time and (2) the effect of fish oil on these parameters when there was a stable hypertriglyceridemia before the source of fat (corn oil) in the diet was replaced by isocaloric amounts of cod liver oil. Our results show an increased triglyceride content in the gastrocnemius muscle with an impaired capacity for glucose oxidation in the basal state and during euglycemic clamp. This was mainly due to a decrease of the active form of pyruvate dehydrogenase complex (PDHa) and an increase of PDH kinase activities. Hyperglycemia, normoinsulinemia, and diminished peripheral insulin sensitivity also were found. Even though there were no changes in the insulin levels, the former metabolic abnormalities were completely reversed when the source of fat was changed from corn oil to cod liver oil. The data also suggest that in the gastrocnemius muscle of rats fed a SRD over an extended period, an increased availability and oxidation of the lipid fuel, which in turn impairs the glucose oxidation, contributes to the abnormal glucose homeostasis and to the peripheral insulin insensitivity. Moreover, the parallel effect on insulin sensitivity, glucose, and lipid homeostasis attained through the manipulation of dietary fat (n-3) in the SRD suggests a role of n-3 fatty acid in the management of dyslipidemia and insulin resistance.     

Diazoxide prevents the development of hormonal and metabolic abnormalities present in rats fed a sucrose rich diet

We have previously reported that normal Wistar rats fed an isocaloric, sucrose-rich (63%) diet (SRD) developed glucose intolerance and elevated triglyceride levels in plasma (P) as well as in heart (H) and liver (L) tissue. This metabolic state was accompanied by hyperinsulinism both in vivo and in vitro, suggesting that a state of insulin resistance has developed. In order to gather information on the role of hyperinsulinemia and glucose intolerance in the development of the above lipid metabolism abnormalities, diazoxide, a known insulin release blocking agent was administered (120 mg/kg/day) together with the diet (SRD + DZX) for 22 days. Control groups fed a standard chow (STD) or the STD plus diazoxide (STD + DZX) were included in the study. Under the present experimental design, DZX was able to prevent the development of hyperinsulinism, glucose intolerance and elevated levels of triacylglycerol in plasma, heart and liver present in animals fed on a sucrose rich diet. Our results suggest that mechanisms involved in the development of this nutritionally induced syndrome may include an interaction of hyperinsulinemia, with a direct effect of sucrose on several steps of lipid metabolism.     

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Background

Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.

Methodology/Principal Findings

We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.

Conclusions/Significance

The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.     

Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids.

The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.     

Soy protein isolate in the presence of cornstarch reduces body fat gain in rats

The objective of the present study was to determine the combined effects of dietary protein and carbohydrate sources on total body energy and protein and fat gains as well as on plasma insulin and glucose and tissue lipoprotein lipase activity in male Sprague-Dawley rats fed semipurified diets for 28 days. The diets varied in both protein and carbohydrate sources, namely, casein-cornstarch, casein-sucrose, soy protein isolate (SPI)-cornstarch, SPI-sucrose, cod protein-cornstarch, and cod protein-sucrose. When SPI was combined with cornstarch, lower total body energy and fat gains were observed compared with the combination of either casein and sucrose, casein and cornstarch, or SPI and sucrose. Plasma glucose and insulin concentrations in addition to total and metabolizable energy intake and body weight gain were lower in rats fed the SPI-cornstarch diet than in those fed the casein-sucrose diet. Feeding the SPI-cornstarch diet compared with feeding either the casein-cornstarch or the SPI-sucrose diet also caused lower plasma glucose concentrations and a concomitant trend (p = 0.06) to reduced energy intake and body weight gain. Therefore, the reducing effects of the SPI-cornstarch diet compared with the casein-cornstarch, the casein-sucrose, and the SPI-sucrose diets on body energy and fat gains may result from reductions in energy intake and in plasma glucose concentrations.     

"In vitro" effects of insulin on the PDH complex of the isolated perfused heart of rats fed a sucrose-rich diet.

We have recently reported that the "in situ" myocardial concentrations of the active form of the Pyruvate Dehydrogenase Complex (PDHa) were significantly decreased in hearts obtained from normal rats fed for 3 weeks on an isocaloric sucrose rich (63%) diet (SRD) when compared to age matched controls fed on the standard laboratory chow (STD). Since, on the one hand SRD rats present glucose intolerance and impaired "in vivo" insulin action and, on the other hand the effects of insulin on the interconversion of heart PDH remains a controversial matter, we found it relevant to study the effects of insulin on the PDH complex in the "in vitro" perfused (Langendorff technique) heart preparations obtained from SRD rats. After a 35 minute perfusion period with 5.5 mM glucose as the only nutrient in the perfusate, PDHa as a percentage of total PDH was found to remain significantly lower in SRD hearts (M +/- SEM 32.6 +/- 2.3) when compared to STD hearts (68.3 +/- 4.6, P less than 0.05) in spite of comparable total PDH activities in both groups of animals. Although the addition of insulin to the perfusate (20 mu/ml) resulted in a significant increase in the percentage of PDHa (45.8 +/- 3.4) of SRD heart, values attained still remained significantly lower than those obtained in STD controls (67.5 +/- 3.6; P less than 0.05). Simultaneously, the addition of insulin to the perfusate, significantly reduced the Acetyl-CoA/CoASH ratio in SRD hearts although this ratio remained still much higher than those observed in STD controls under the same experimental conditions.     

The effect of iron overload on urinary excretion of immunoreactive prostaglandin E2

The effect of in vivo lipid peroxidation on the excretion of immunoreactive prostaglandin E2 (PGE2) in the urine of rats was studied. Weanling, male Sprague-Dawley rats were fed a vitamin E-deficient diet containing 10% tocopherol-stripped corn oil (CO) or 5% cod liver oil (CLO) with or without 40 mg dl-alpha-tocopheryl acetate/kg. To induce a high, sustained level of lipid peroxidation, some rats were injected intraperitoneally with 100 mg of iron as iron dextran after 10 days of feeding. Iron overload stimulated in vivo lipid peroxidation in rats, as measured by the increase in expired ethane and pentane. Dietary vitamin E reversed this effect. Rats fed the CLO diet excreted 9.5-fold more urinary thiobarbituric acid-reactive substances (TBARS) than did rats fed the CO diet. Iron overload increased the excretion of TBARS in the urine of rats fed the CO diet, but not in urine of rats fed the CLO diet. Dietary vitamin E decreased TBARS in the urine of rats fed either the CO or the CLO diet. Iron overload decreased by 40% the urinary excretion of PGE2 by rats fed the CO diet, and dietary vitamin E did not reverse this effect. Iron overload had no statistically significant effect on urinary excretion of PGE2 by rats fed the CLO diet. A high level of lipid peroxidation occurred in iron-treated rats, as evidenced by an increase in alkane production and in TBARS in urine in this study, and by an increase in alkane production by slices of kidney from iron-treated rats in a previous study [V. C. Gavino, C. J. Dillard, and A. L. Tappel (1984) Arch. Biochem. Biophys. 233, 741-747]. Since PGE2 excretion in urine was not correlated with these effects, lipid peroxidation appears not to be a major factor in renal PGE2 flux.     

Protective effect of ascorbic acid against lipid peroxidation and oxidative damage in cardiac microsomes

Effects of feeding sucrose rich diet supplemented with and without the insulinmimetic agent vanadate for a period of six weeks were studied in rats. Sucrose diet caused hypertriglyceridemia (140% increase), hyperinsulinemia (120% increase) and significant elevations in the levels of glucose (p<0.001) and cholesterol (p<0.05) in plasma as compared to control starch fed rats. Activities of hepatic lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme increased by 100–150% as a result of sucrose feeding. However, glycogen content and the activities of glycogen synthase and phosphorylase in liver remained unaltered in these animals. The plasma levels of triacylglycerols and insulin in the rats fed on vanadate supplemented sucrose diet were 65% and 85% less, respectively as compared to rats on sucrose diet without vanadate. The concentrations of glucose and cholesterol in plasma and the activities of lipogenic enzymes in liver did not show any elevation in sucrose fed rats when supplemented with vanadate. These data indicate that the sucrose diet-induced metabolic aberrations can be prevented by the insulin-mimetic agent, vanadate.     

Effects of a Fat Substitute,Sucrose Polyester,on Food Intake,Body Composition,and Serum Factors in Lean and Obese Zucker Rats

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight-week-old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one-half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control-fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O-FS) gained less weight as compared to obese control-fed animals (O-C). Lean rats given fat substitute (L-FS) did not have significantly different body weights as compared to the L-C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O-FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O-C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.     

Plasma lipoprotein cholesterol and triglycerides and lipoprotein lipase activity in epididymal white adipose tissue of rats fed high sucrose or high corn oil diets

The present study was undertaken to compare plasma lipoprotein lipid composition, as well as white adipose tissue lipoprotein lipase activity, in rats fed purified diets high in either sucrose or corn oil. The experimental diets (65% of calories as sucrose or corn oil, 15% as the opposite nutrient, and 20% as casein) were given ad libitum for 4 weeks. An additional group was fed a nonpurified diet as a reference diet. Both sucrose and oil diets were spontaneously consumed in isocaloric amounts by the animals. Despite energy intakes that were 35% lower than that of the reference group, the sucrose and oil groups exhibited final body weights that were only 6 and 9% lower, respectively, than that of the reference group, and accumulated more fat in the epididymal depots. Postprandial as well as fasting total cholesterol levels were similar in the sucrose and oil groups, while the high-density lipoprotein to total cholesterol ratio was highest in the animals fed corn oil. In both the fasted and fed states, plasma total triglyceride levels were 73% higher in the sucrose group than in the corn oil group. The largest triglyceride differences due to diet were observed in the chylomicron + very-low-density lipoprotein fraction. The oil-fed rats accumulated large amounts of triglycerides in their livers. Postprandial lipoprotein lipase activity in epididymal adipose tissue was almost twice as high in the sucrose group as in the oil group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The mouse bioassay for the detection of estrogenic activity in rodent diets: III. Stimulation of uterine weight by dextrose, sucrose and corn starch

We have shown previously that mice fed the American Institute of Nutrition (AIN-76A) purified diet experience a significant increase in uterine:body weight (U:BW) ratios when compared to the U:BW ratios of mice fed a closed formula natural ingredient diet (Certified Rodent Chow #5002) for 7 days. The AIN-76A purified diet contains 5% corn oil and 65% carbohydrates with 50% of the carbohydrates coming from sucrose or dextrose and 15% from corn starch. The objective of this study was to determine whether the fat and carbohydrate content contributed to the unexpected uterine growth promoting activity observed in mice fed the AIN-76A diet. Estrogen bioassays were performed using CD-1 mice weaned at 15 days of age and assigned randomly to the negative control diet (Certified Rodent Chow #5002) or to the positive control diet (#5002) containing 4 or 6 ppb DES for comparison or to the test diets. The test diets were prepared by adding sucrose, dextrose, corn starch, corn oil or soybean oil to the #5002 negative control diet at 10% w/w concentration. Uterine:BW ratios were determined at 7 days post-feeding. The uterine weights and the U:BW ratios of mice fed the test diets containing dextrose, corn starch, or corn oil, were increased significantly (P less than 0.05) over those of mice fed the negative control diet. The uterine weights and U:BW ratios of mice fed the test diets containing sucrose or soybean oil also were increased over those of mice fed the negative control diet. These increases in uterine weights and U:BW ratios were similar to the increases in uterine weights and U:BW ratios of mice fed the positive control diet containing 4 ppb DES. It was concluded that the fats and carbohydrates caused preferential increases in uterine weights and in U:BW ratios and may account for the estrogen-like uterine growth promoting activity observed in mice fed the AIN-76A purified diet.     

The control of lipogenesis by dietary linoleic acid and its influence on the deposition of fat.

The replacement of dietary starch by sucrose results in an increase in hepatic lipogenesis in the rat. When corn oil (4% by weight or 9% of the energy content of the diet) was included with the sucrose (20% by weight, 20% of the energy content) the lipogenic effect of the sucrose was completely suppressed. In contrast, when beef tallow replaced the corn oil, the induced activity caused by the sucrose was reduced by only approximately 20%. No significant differences were observed between males and females. These diets containing sucrose supplemented with either 4% (w/w) corn oil or 4% (w/w) beef tallow, were then used to ascertain whether or not the effects on hepatic lipogenesis were reflected in changes in the amount of fat deposited during growth from 4--24 weeks of age. It was shown that the percentage body fat was only statistically different (P less than 0.05) when animals fed sucrose-supplemented diets were compared with animals fed diets supplemented with sucrose and beef tallow. However, there were no significant differences in total carcass weight of these rats. The results are discussed in terms of the relative contribution of liver and adipose tissue to total lipogenesis and the factors which control the lipogenic activity in the two tissues.     

Effects of dietary lipid source on reproductive performance and tissue lipid levels of Nile tilapia Oreochromis niloticus (Linnaeus) broodstock

Nile tilapia were fed diets supplemented with one of the following lipid sources at 5% level: cod liver oil, corn oil, soybean oil, a coconut oil-based cooking oil or a combination of cod liver oil and corn oil (1 : 1). The control diet had no lipid supplement and tad fish meal as a sole protein source. A diet with soybean meal as a protein source was also tested. The number of females that spawned, spawning frequency, number of fry per spawning, and total fry production were increased at varying degrees by the supplemental lipid sources except for the cod liver oil. Fish fed the soybean oil diet tad the best overall reproductive performance over a 24-week period. Fish fed the cod liver oil diet had the highest weight gain but the poorest reproductive performance. The suplemental lipids significantly increased crude fat levels in the liver and ovaries. Both males and females Ld the cod liver oil diet had the highest levels of fat in the liver and muscle. The ratio of total n-6/n-3 fatty acid in the liver, ovaries and testes was influenced by the supplemental lipid sources. It was highest in fish fed either the soybean oil diet, the corn oil diet, or the soybean meal diet and lowest in fish fed the control diet or the cod liver oil diet.     

Protein-restriction diet during the suckling phase programs rat metabolism against obesity and insulin resistance exacerbation induced by a high-fat diet in adulthood

Protein restriction during the suckling phase can malprogram rat offspring to a lean phenotype associated with metabolic dysfunctions later in life. We tested whether protein-caloric restriction during lactation can exacerbate the effect of a high-fat (HF) diet at adulthood. To test this hypothesis, we fed lactating Wistar dams with a low-protein (LP; 4% protein) diet during the first 2 weeks of lactation or a normal-protein (NP; 23% protein) diet throughout lactation. Rat offspring from NP and LP mothers received a normal-protein diet until 60 days old. At this time, a batch of animals from both groups was fed an HF (35% fat) diet, while another received an NF (7% fat) diet. Maternal protein-caloric restriction provoked lower body weight and fat pad stores, hypoinsulinemia, glucose intolerance, higher insulin sensitivity, reduced insulin secretion and altered autonomic nervous system (ANS) function in adult rat offspring. At 90 days old, NP rats fed an HF diet in adulthood displayed obesity, impaired glucose homeostasis and altered insulin secretion and ANS activity. Interestingly, the LP/HF group also presented fat pad and body weight gain, altered glucose homeostasis, hyperleptinemia and impaired insulin secretion but at a smaller magnitude than the NP-HF group. In addition, LP/HF rats displayed elevated insulin sensitivity. We concluded that protein-caloric restriction during the first 14 days of life programs the rat metabolism against obesity and insulin resistance exacerbation induced by an obesogenic HF diet.     

Effects of chronic modification of dietary fat and carbohydrate on the insulin, corticosterone and metabolic responses of rats fed acutely with glucose, fructose or ethanol

1. Male rats were fed for 14 days on powdered diets containing (by weight) 53% of starch, or on diets in which 20g of starch per 100g of diet was replaced by lard or corn oil. They were then fed acutely by stomach tube with a single dose of glucose, fructose or ethanol of equivalent energy contents, or with 0.15m-NaCl. The serum concentrations of corticosterone, insulin, glucose, glycerol, triacylglycerol and cholesterol were measured up to 6h after this treatment. 2. Feeding saline (0.9% NaCl) acutely to the rats maintained on the three powdered diets produced a small transient increase in circulating corticosterone that was similar to that in rats maintained on the normal 41B pelleted diet. 3. Feeding glucose acutely to the rats on the powdered diets produced peak concentrations of corticosterone that were 2–3-fold higher than those seen in rats maintained on the 41B diet. The duration of this response increased in the order starch diet<lard diet<corn-oil diet. This abnormal corticosterone response to glucose feeding appeared to be responsible for an increased activity in phosphatidate phosphohydrolase in the livers of rats fed the starch and lard diets of 2.9- and 4.9-fold respectively. The latter increase was similar to that produced by ethanol, whereas glucose did not increase the phosphohydrolase activity in the liver of rats maintained on the 41B diet. 4. Feeding fructose acutely produced even more marked increases than glucose in the concentrations of circulating corticosterone in rats given the powdered diets, but unlike glucose did not increase circulating insulin. The duration of the corticosterone response again increased in the order starch diet<lard diet<corn-oil diet. The concentrations of circulating glucose were increased by fructose feeding in rats maintained on these diets, but they were not altered in the rats maintained on the 41B pellets. A prolonged increase in serum corticosterone concentrations was also observed when fructose was fed to rats maintained on pelleted diets enriched with corn oil or beef tallow rather than with starch or sucrose. However, these effects were less marked than those seen with rats fed on the powdered diets. 5. These results are discussed in relation to the mechanism whereby high dietary fat exaggerates the effects of ethanol, fructose and sorbitol in stimulating triacylglycerol synthesis in the liver.     

Changes in glucose tolerance and leptin responsiveness of rats offered a choice of lard, sucrose, and chow

Rats offered chow, lard, and 30% sucrose solution (choice) rapidly become obese. We tested metabolic disturbances in rats offered choice, chow+lard, or chow+30% sucrose solution [chow+liquid sucrose (LS)] and compared them with rats fed a composite 60% kcal fat, 7% sucrose diet [high-fat diet (HFD)], or a 10% kcal fat, 35% sucrose diet [low-fat diet (LFD)]. Choice rats had the highest energy intake, but HFD rats gained the most weight. After 23 days carcass fat was the same for choice, HFD, chow+lard, and chow+LS groups. Glucose clearance was the same for all groups during an intraperitoneal glucose tolerance test (GTT) on day 12, but fasting insulin was increased in choice, LFD fed, and chow+LS rats. By contrast, only choice and chow+LS rats were resistant to an intraperitoneal injection of 2 mg leptin/kg on day 17. In experiment 2 choice rats were insulin insensitive during an intraperitoneal GTT, but this was corrected in an oral GTT due to GLP-1 release. UCP-1 protein was increased in brown fat and inguinal white fat in choice rats, and this was associated with a significant increase in energy expenditure of choice rats during the dark period whether expenditure was expressed on a per animal or a metabolic body size basis. The increase in expenditure obviously was not great enough to prevent development of obesity. Further studies are required to determine the mechanistic basis of the rapid onset of leptin resistance in choice rats and how consumption of sucrose solution drives this process.     

Hepatic expression of apolipoprotein A-I gene in rats is upregulated by monounsaturated fatty acid diet

The effect of the degree of dietary fat saturation on the hepatic expression of apolipoprotein A-I mRNA was studied in male rats. Animals were maintained for two months on a high fat diet (40% w/w) containing 0.1% cholesterol. Two groups of control animals received either chow diet or chow plus 0.1% cholesterol, while experimental groups received their fat supplement as coconut, corn or olive oil respectively. Dietary cholesterol did not affect apolipoprotein A-I mRNA levels as compared to control animals. Corn oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA than those receiving cholesterol, or coconut oil plus cholesterol. Olive oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA when compared to all other dietary groups. Our data indicate that monounsaturated fatty acids supplied as olive oil play a major role in regulating the hepatic expression of apolipoprotein A-I in male rats.     

The effect of insulin on the uptake and metabolic fate of glucose in isolated perfused hearts of dyslipemic rats

Male Wistar rats chronically (15 weeks) fed a sucrose-rich diet (SRD; 63% w/w) developed hypertriglyceridemia and impaired glucose homeostasis. Hearts from these animals were isolated and perfused using the Langendorff recirculating method. Glucose at levels similar to those found in the animal in vivo was used as the only exogenous substrate. The hearts were perfused for 30 minutes in the presence or absence of insulin (30 mU/mL) in the perfusion medium. In the absence of the hormone, glucose uptake was impaired and the glucose utilization was reduced, with a significant increase of lactate release. Glucose oxidation, which was estimated from the activation state of the enzyme pyruvate dehydrogenase complex (PDHc), was depressed mainly due to both an increase of PDH kinase and a decrease of PDHa (active form of PDHc) activities. Although the addition of insulin in the perfusion medium improved the above parameters, it was unable to normalize them. The present results suggest that at least two different mechanisms might contribute to insulin resistance and to the impaired glucose metabolism in the perfused hearts of the dyslipemic SRD-fed animals: (1) reduced basal and insulin-stimulated glucose uptake and its utilization or (2) increased availability and oxidation of lipids (low PDHa and high PDH kinase activities), which in turn decrease glucose uptake and utilization. Thus, this nutritional experimental model may be useful to study how impaired glucose homeostasis, increases plasma free fatty acid levels and hypertriglyceridemia could contribute to heart tissue malfunction.     

Early exposure to a high-fat diet has more drastic consequences on metabolism compared with exposure during adulthood in rats

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.