The effects of various carbohydrates on sympathetic activity in heart and interscapular brown adipose tissue of the rat

The present studies were undertaken to determine the effect of various carbohydrates on sympathetic nervous system (SNS) activity. Tritiated-norepinephrine (3H-NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed either chow or chow plus 50% caloric supplements of fructose, sucrose, dextrose, or corn starch. Additional studies were performed to examine whether absorption of carbohydrate plays a role in the SNS response, and to determine whether sweet taste in the form of artificial sweeteners may influence SNS activity. After five to ten days on the respective diets, 3H-NE turnover was increased to a similar extent by all carbohydrates tested (from 38% to 160% greater than controls in different studies). Addition of acarbose (which impairs sucrose absorption) to a sucrose-supplemented diet abolished the SNS stimulatory response, whereas cholestyramine (a drug that blocks fat absorption) had no effect. Finally, the addition of saccharin or aspartame to a chow diet failed to alter SNS activity. Thus, caloric supplementation with several carbohydrates, in addition to sucrose, stimulates both cardiac and IBAT SNS activity, absorption of carbohydrate is required for this effect, and noncaloric sugar substitutes do not alter SNS function.     

Effects of LY104119, a thermogenic weight-reducing compound, on norepinephrine concentrations and turnover in obese and lean mice

Dopamine (DA) accumulation in interscapular brown adipose tissue (IBAT), heart, and liver was linear for more than 60 min after injection of 1-cyclohexyl-2-mercapto-imidazole (CHMI), a DA beta-hydroxylase inhibitor, into mice and served as an index of the rate of synthesis of norepinephrine (NE) in these tissues. There was a marked diurnal rhythm of DA accumulation in all three tissues of mice fed ad libitum, the rhythm being dampened in obese mice in IBAT and liver but not in heart. LY104119 acutely decreased NE concentration in IBAT, heart and liver, but not in brain, and it also decreased DA accumulation after CHMI in IBAT, heart and liver. Chronic administration of LY104119 at doses that stimulated thermogenesis and reduced body weight decreased NE turnover in heart and liver but increased NE turnover in IBAT. These data suggest that the increased thermogenesis in IBAT after chronic LY104119 treatment may be mediated by increased noradrenergic tone.     

Effects of diet and exercise on the in vivo rates of the triglyceride-fatty acid cycle in adipose tissue and muscle of the rat

The effects of feeding a low-protein diet (5 percent w/w) and daily exercise on the rates of substrate (futile) cycling between triglyceride and fatty acids (TG-FA cycle) were studied in rats in vivo using a radiochemical assay that involves following the incorporation of tritium from 3H-H2O into the fatty acid and glycerol moieties of triglyceride. Sixty-four rats were fed either a purified control diet (COND) consisting of 70 percent carbohydrate, 20 percent protein, 5 percent fat or an experimental low protein (LPD) diet consisting of 80 percent carbohydrate, 5 percent protein and 10 percent fat (w/w) and were either exercised six days weekly or remained sedentary for six weeks. Both LPD and exercise training (EXT) were found to increase significantly the rate of TG-FA substrate cycling above the rates observed in dietary and sedentary control groups. The LPD increased significantly the rate of cycling in interscapular brown adipose (IBAT), while adipose (WAT) and diaphragm muscle. EXT increased the rates of substrate cycling in soleus, heart, and diaphragm muscle and WAT. Rate of cycling in cardiac or skeletal muscle was one-twentieth that found in adipose tissue. There were also sex differences in the rate of substrate cycling. Substrate cycling in soleus and heart muscle of male animals were consistently higher than respective female treatment groups. Sedentary and EXT LPD animals weighed significantly less than but consumed a similar amount of food to the respective COND animals. These data provide the first in vivo evidence that the rate of substrate cycling can be increased by diet or by exercise training. The possible importance of TG-FA and other substrate cycles on efficiency of energy metabolism and etiology of obesity are discussed.     

Reduced norepinephrine turnover in interscapular brown adipose tissue of obese rats after ovariectomy

Norepinephrine (NE) turnover, which is a reliable indicator of sympathetic nervous system (SNS) activity, was measured in the interscapular brown adipose tissue (IBAT), heart, and pancreas of ovariectomized (OVX), sham-operated rats receiving injections of estradiol benzoate (EB). Ovariectomized rats (OVX rats) ate much more than controls and became obese, whereas the administration of EB to obese OVX rats decreased their food intake to the level below that of sham-operated animals and body weight to the level of sham controls. The results from studies using the inhibition of NE biosynthesis with alpha-methyl-p-tyrosine or radiolabeled NE to measure NE turnover significantly demonstrated reductions in SNS activity in IBAT of OVX rats than in sham controls, whereas the injections of EB to OVX rats significantly restored the decrease of NE turnover in IBAT. NE turnover in heart and pancreas were similar in these three groups. It is suggested that reduced NE turnover in IBAT may be a major factor in the development of obesity after ovariectomy (OVX).     

Effects of monosodium glutamate and gold thioglucose on dietary regulation of sympathetic nervous system activity in rodents

Neonatal administration of monosodium glutamate (MSG) disrupts hypothalamic regulation of a number of neuroendocrine systems. Studies described in this report using techniques of norepinephrine (NE) turnover examined sympathetic nervous system (SNS) activity in heart and interscapular brown adipose tissue (IBAT) of animals given MSG as neonates. Although in every experiment overall rates of NE turnover were lower in MSG-treated mice and rats, the differences were due exclusively to diminished tissue NE content, especially in IBAT. Fractional rates of NE turnover did not differ between groups. In contrast to animals with lesions in the ventromedial hypothalamus produced by gold thioglucose (AuTG) or electric current, MSG-treated mice and rats varied SNS activity in heart and IBAT in accord with changes in nutrient intake. Thus, SNS activity, both at baseline and in response to dietary manipulation, is probably not affected by neonatal MSG administration.     

Metabolic and hormonal investigations in long-term streptozotocin diabetic rats on different dietary regimens

Summary Groups of diabetic rats (65 mg/kg streptozotocin SC) were fed ad lib on three different dietary regimens for 43 weeks: a standard control diet (68% of calories as carbohydrate, 20% as protein, and 12% as fat), a low carbohydrate high protein diet (6% carbohydrate, 63% protein, 31% fat) or a low carbohydrate-high fat diet (5% carbohydrate, 75% fat, 20% protein). The high fat diet resulted in a fall of blood glucose from 700 to 350 mg/100 ml. Rats fed the high protein diet showed a similar initial decrease in blood glucose concentration, and a further improvement was evident from the 28th week on. After 43 weeks blood glucose levels were below 180 mg/100 ml and glycosuria below 100 mg/24 h in all rats fed the high protein diet. When rats exhibiting blood glucose levels below 180 mg/dl were transferred temporarily to standard diet blood glucose levels increased and marked glycosuria was observed. Rats on the standard diet maintained blood glucose concentrations greater than 500 mg/100 ml and glycosuria of about 16 g/24 h throughout the experiment. The pancreatic insulin content at death of rats fed the standard diet or the high fat diet was 1% of normal rats, whereas the values for the rats on the high protein diet were increased to 9%. Animals fed the low carbohydrate diets showed greater weight gain. In the high fat diet group there was a marked rise after 43 weeks in plasma triglycerides, free fatty acids, 3-hydroxybutyrate and acetoacetate in the plasma. Urea excretion was raised in the animals on the high protein diet. Thus, treatment with low carbohydrate diets for 10 months regardless of fat and protein content markedly improved the diabetic state of rats.     

The effect of LXRα, ChREBP and Elovl6 in liver and white adipose tissue on medium- and long-chain fatty acid diet-induced insulin resistance

Aims

We aimed to investigate the effects of LXRα, ChREBP and Elovl6 in the development of insulin resistance-induced by medium- and long-chain fatty acids.

Methods

Sprague Dawley rats were fed a standard chow diet (Control group) or a high-fat, high sucrose diet with different fat sources (coconut oil, lard, sunflower and fish oil) for 8 weeks. These oils were rich in medium-chain saturated fatty acids (MCFA group), long-chain saturated fatty acids (LCFA group), n-6 and n-3 long-chain polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA groups), respectively, which had different chain lengths and degrees of unsaturation. Hyperinsulinemic–euglycemic clamp with [6-³H] glucose infusion was performed in conscious rats to assess hepatic insulin sensitivity.

Results

LCFA and n-6 PUFA groups induced hepatic insulin resistance and increased liver X receptor α (LXRα), carbohydrate response element binding protein (ChREBP) and long-chain fatty acid elongase 6 (Elovl6) expression in liver and white adipose tissue (WAT). Furthermore, LCFA and n-6 PUFA groups suppressed Akt serine 473 phosphorylation in liver and WAT. By contrast, in liver and WAT, MCFA and n-3 PUFA groups decreased LXRα, ChREBP and Elovl6 expression and improved insulin signaling and insulin resistance, but Akt serine 473 phosphorylation was not restored by MCFA group in WAT.

Conclusions

This study demonstrated that the mechanism of the different effects of medium- and long-chain fatty acids on hepatic insulin resistance involves LXRα, ChREBP and Elovl6 alternations in liver and WAT. It points to a new strategy for ameliorating insulin resistance and diabetes through intervention on Elovl6 or its control genes.     

The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo.

OBJECTIVE: To determine: (a) whether active pyruvate dehydrogenase (PDHa) activity in interscapular brown adipose tissue (IBAT) is acutely regulated by altered insulin status at euglycaemia; (b) the relationship between glucose uptake/phosphorylation and PDHa activities in IBAT in vivo; and (c) the impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in IBAT in comparison with that exerted on various white adipose tissue depots. DESIGN: Rats were provided with either a standard diet (8% fat, 72% carbohydrate, by energy) or a diet moderately high in saturated fat (47%, by energy) and low in carbohydrate (33%, by energy) for four weeks. Rats were studied in the absorptive state, in the post-absorptive state or after 2.5 h euglycaemic hyperinsulinaemia. Tissues sampled included IBAT and four white adipose tissue depots, two abdominal (parametrial (PM) and perirenal (PR)) and two superficial (subcutaneous (SC) and interscapular (IS)). MEASUREMENTS: Whole-body glucose disposal was estimated using [3-3H]glucose. Glucose uptake/phosphorylation in vivo was estimated using 2-deoxy[1-3H]-D-glucose. Insulin action was evaluated using the euglycaemic-hyperinsulinaemic clamp technique. PDHa activity was assayed spectrophotometrically in freeze-clamped tissue extracts. PDH kinase (PDK) activities were assayed in mitochondrial extracts by rates of ATP-dependent PDHa inactivation. RESULTS: Whole-body glucose disposal was decreased by high-fat-feeding in the post-absorptive state (P < 0.05) and during euglycaemic hyperinsulinaemia (P < 0.01). Glucose transport/phosphorylation in IBAT was decreased by high-fat feeding in the absorptive (P < 0.001) and post-absorptive states (by 84%, P < 0.05) and during steady-state euglycaemic hyperinsulinaemia (by 73%, P < 0.001). IBAT PDHa activities were suppressed by high-fat feeding. Euglycaemic hyperinsulinaemia in post-absorptive control rats increased PDHa activities in IBAT (P < 0.001) to values comparable to those found in the absorptive state. Although IBAT PDHa activities were increased by euglycaemic hyperinsulinaemia in post-absorptive high-fat-fed rats, they remained lower (by 55%; P < 0.01) than those of controls. The failure of hyperinsulinaemia to normalise IBAT pyruvate dehydrogenase complex (PDHC) activities in high-fat-fed rats was associated with a stable 1.4-fold increase in IBAT PDK activity. High-fat feeding decreased glucose utilisation rates in the post-absorptive state in IS, but not in SC, PM or PR white adipose tissue depots. Euglycaemic hyperinsulinaemia significantly increased glucose utilisation in three out of the four depots of the control rats, but did not elicit statistically-significant changes in high-fat-fed rats. High-fat feeding influenced PDHa activity in PR, but was without significant effect on PDHa activity in PM, SC and IS. CONCLUSIONS: The results demonstrate that PDHa activity in the IBAT of rats maintained on standard diet responds to changes in insulin concentrations over the low physiological range, and that inactivation of PDHa in IBAT after feeding a diet moderately high in saturated fat is a consequence of the induction of tissue insulin resistance. Effects of this dietary regime on PDHa activity are paralleled by changes in insulin-stimulated glucose uptake/phosphorylation by IBAT in vivo, and IBAT is specifically targeted, with only moderate effects in white adipose tissue. The finding of impaired activation of BAT glucose transport/phosphorylation and PDHa activity in response to insulin may contribute to impaired thermogenesis in rats maintained on diets containing a relatively high proportion of saturated fat.     

Developmental plasticity in sympathetic nervous system response to fasting in adipose tissues of male rats

While fasting suppresses sympathetic nervous system (SNS) activity in most peripheral tissues, the response of sympathetic nerves in white adipose tissue (WAT) is reportedly stimulatory. To confirm this finding and to determine if the fasting response in WAT is susceptible to developmental modification, SNS activity was compared in fed and fasted animals using techniques of [3H]norepinephrine ([3H]NE) turnover. Studies were performed in commercially reared 7-week-old male rats, in male rats reared in the local vivarium, and in male rats reared until 30 days of age at either 18 degrees C or 30 degrees C. In commercially reared animals, [3H]NE turnover was elevated in epididymal fat during the second day of fasting, a response not seen during the preceding or succeeding day of fasting. On the other hand, in rats reared from birth in the local vivarium a 1-day fast led to suppression of SNS activity in epididymal fat. In rats reared at 18 degrees C for the first 30 days of life, fasting suppressed SNS activity in retroperitoneal fat in contrast to the absence of this response noted in 30 degrees C-reared rats. These studies demonstrate that sympathetic responses in WAT to fasting in young adult, male rats are susceptible to modification by the environmental conditions present during the first month of life.     

Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation

Melanocortins are implicated in the control of energy intake/expenditure. Centrally administered melanotan II (MTII), a synthetic melanocortin 3/4-receptor agonist, decreases adiposity beyond that accountable by food intake decreases. Melanocortin-4 receptor (MC4-R) mRNA is expressed on sympathetic nervous system (SNS) outflow neurons to white adipose tissue (WAT) in Siberian hamsters, suggesting a role in lipid mobilization. Therefore, we tested whether third ventricular injections of MTII increased sympathetic drive to WAT and interscapular brown adipose tissue (IBAT) using norepinephrine turnover (NETO) as a measure of sympathetic drive. We also tested for MTII-induced changes in lipolysis-related WAT gene expression (beta3-adrenoceptors, hormone sensitive lipase) and IBAT thermogenesis (beta3-adrenoceptor, uncoupling protein-1). Finally, we tested whether third ventricularly injected MTII, a highly selective MC4-R agonist (cyclo[beta-Ala-His-D-Phe-Arg-Trp-Glu]NH2) increased or agouti-related protein decreased IBAT temperature in hamsters implanted with sc IBAT temperature transponders. Centrally administered MTII provoked differential sympathetic drives to WAT and IBAT (increased inguinal WAT, dorsosubcutaneous WAT and IBAT NETO, but not epididymal WAT and retroperitoneal WAT NETO). MTII also increased circulating concentrations of the lipolytic products free fatty acids and glycerol but not plasma catecholamines, suggesting lipid mobilization via WAT SNS innervation and not via adrenal medullary catecholamines. WAT or IBAT gene expression was largely unaffected by acute MTII treatment, but IBAT temperature was increased by MTII and the MC4-R agonist and decreased by agouti-related protein. Collectively, this is the first demonstration of central melanocortin agonist stimulation of WAT lipolysis through the SNS and confirms melanocortin-induced changes in BAT thermogenesis.     

Blood constituents and hepatic lipids in rats fed sucrose or starch with or without cyclamate

To study the effect of type of dietary carbohydrate and cyclamate on selected tissue components, rats were fed basal diets that contained sucrose or cornstarch: dextrin (2:1) with 0, 2, or 10% calcium cyclamate. Substitution of starch:dextrin for sucrose in the basal diet did not significantly affect the concentrations of blood hemoglobin, serum protein, cholesterol or total lipids in liver, or weight gain of the animals. Substitution of 2% cyclamate for sucrose did not appear to affect significantly the parameters studied, except that liver weight and total amino acid concentration decreased. Animals fed starch:dextrin with 2% cyclamate had lower weight gains than those of their respective controls, whereas liver cholesterol and total lipid concentrations were increased. Dietary cyclamate decreased the liver weight of all experimental groups. Weight gains of animals fed sucrose or starch:dextrin with 10% cyclamate in replacement of carbohydrate were, respectively, 41 and 58% lower than those of their respective controls. Substitution of 10% cyclamate for sucrose or starch:dextrin decreased blood hemoglobin. The total concentration of essential amino acids in sera of rats fed 10% cyclamate with sucrose or starch:dextrin approached or exceeded that of the respective controls. The data indicate that the effect of cyclamates on the level of certain tissue components may be related to the type of carbohydrate fed with cyclamate.     

High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis

High-fat diet intake often leads to obesity, insulin resistance and hypertension, which present a common and detrimental health problem. However, precise mechanism underlying tissue damage due to high-fat diet-induced obesity has not been carefully elucidated. The present study was designed to examine the effect of high-fat diet intake on visceral advanced glycation end products (AGEs) formation, nuclear O-Glc-NAc modification and apoptosis in heart, liver and kidney. Adult male Sprague-Dawley weight-matched rats were fed for 12 weeks with a high-fat diet (45% kcal from fat) or an isocaloric low-fat diet (10% kcal from fat). High-fat diet feeding significantly elevated body weight. Blood pressure and heart rate were comparable between the two rat groups. Competitive enzyme-linked immunosorbent assay showed significantly elevated serum AGE levels, visceral AGE formation, caspase-3 activation and cytoplasmic DNA fragmentation in heart and liver but not kidney samples of high-fat diet fed rats compared with those from low-fat diet fed group. Western blot analysis further revealed that high-fat diet feeding induced overt nuclear O-Glc-NAc modification and p38 mitogen-activated protein kinase activation in heart and liver although not in kidney samples of the high-fat diet-fed rats. Collectively, our results indicated that high-fat diet intake is associated with obesity accompanied by elevated serum and visceral AGEs, visceral post-translational nuclear O-Glc-NAcylated modification and apoptosis, which may contribute to high-fat diet-induced tissue damage.     

Thermogenesis and brown adipose tissue activity in high fat fed Osborne-Mendel rats

The consequences of hyperlipidic feeding on interscapular brown adipose tissue (IBAT) activity were examined in the cold-acclimated rat. Male Osborne-Mendel rats (7 weeks old) were exposed for 10 weeks at either 28 or 5 degrees C. The rats were fed a semipurified diet (normal fat (NL): 5% lard; high fat (HL): 54% lard) for the last 9 weeks. IBAT weight was greater in HL than in NL rats. This increase was entirely due to accumulation of neutral lipids. Among different IBAT components (proteins, DNA, phospholipids) no variations were observed in HL 28 degrees C rats. HL diet did not modify lipoprotein lipase and cytochrome oxidase activities, but an increase in purine nucleotide binding (taken as an index of thermogenic activity) was observed in HL 28 degrees C rats. Cold acclimation led to comparable stimulation in NL and HL rats. The calorigenic effect of norepinephrine in vivo was not modified by HL diet. Study of arteriovenous differences showed that IBAT fatty acid and glycerol release by norepinephrine was slightly increased in HL 28 degrees C rats. No effect of HL diet was observed at 5 degrees C. These results indicate that HL feeding leads to a moderate increase in the IBAT thermogenic capacity of Osborne-Mendel rats. HL diet does not modify the normal development of nonshivering thermogenesis when rats are kept in a cold environment.     

Glucose-induced sympathetic activation in obesity-prone and resistant rats

Half of the 3-month-old male Sprague-Dawley rats fed a diet enriched in calories, sucrose and fat (CM diet) for 3 months developed diet-induced obesity (DIO) while the remainder were diet resistant (DR), gaining the same amount of weight as chow-fed controls. DIO was associated with basal hyperinsulinemia and 196 percent heavier retroperitoneal fat pads than DR and chow-fed rats. Intravenous glucose infusion (lg/kg) also produced greater insulin release in DIO rats associated with a 25 percent reduction in glucose disposal rates; areas under the insulin curve were 273 and 51 percent higher than chow-fed and DR rats, respectively. DR rats, on the other hand, showed normal glucose disposal rates but increased insulin release to a glucose load (148 percent greater area under the curve than chow-fed rats). Glucose infusion produced activation of the sympathetic nervous system with release of norepinephrine (NE) into the plasma in chow-fed and DIO but not DR rats which had 40-50 percent lower areas under the NE curve. Also, the areas under the NE curve correlated with body weight gain (r = 0.632; P = 0.040) and retroperitoneal fat pad weight (r = 0.707; P = 0.030) in DR and DIO rats suggesting that glucose-induced sympathetic activation was in some way related to an underlying mechanism of body weight regulation in Sprague-Dawley rats.     

Increase of microsomal glucose-6-phosphatase activity after chronic ethanol administration

To study the effect of chronic ethanol administration on the activity of hepatic microsomal glucose-6-phosphatase, female rats were pair-fed liquid diets with 36% of total calories either as ethanol or isocaloric carbohydrate (controls). The remainder of the diet contained 35% of total calories as fat, 18% as protein, and 11% as additional carbohydrate. Six weeks of ethanol feeding as isocaloric substitution for carbohydrate increased significantly the activity of glucose-6-phosphatase (expressed per mg microsomal protein) both in fed (38%; p < 0.001) and fasted 18%; p < 0.02) rats. When expressed per unit of body weight, the enzyme activity was increased even further both in fed (66%; p < 0.01) and fasted (43%; p < 0.01) rats. Another group of rats received diets containing 36% of calories either as ethanol or isocaloric fat. The remainder of the diet contained 11% of total calories as carbohydrate, 18% as protein, and 35% as additional fat. Six weeks of this ethanol feeding as isocaloric substitution for fat again increased glucose-6-phosphatase activity significantly. Ultracentrifugation in a Cs⁺-containing sucrose gradient to separate rough and smooth microsomes revealed that the increase in glucose-6-phosphatase activity after ethanol feeding occurred mainly in the smooth microsomal membranes.     

Development of compensatory thermogenesis in response to overfeeding in hypothyroid rats.

Intact or surgically thyroidectomized (Tx) adult male Wistar rats, weighing 150-200 g, were fed a standard chow diet (approximately 1.8 Cal/g) or a high calorie (approximately 3.8 Cal/g) diet (cafeteria diet) for up to 30 days. Daily energy intake was about 5-fold higher in the rats fed the cafeteria diet regardless of their thyroid status. The cafeteria diet caused the retroperitoneal white fat pad to increase by approximately 2-fold, the volume of isolated white adipocytes to increase by 2-fold, and the total body fat to increase by a factor of approximately 3, again regardless of thyroid status. It also increased basal metabolic rate by about 20% in intact rats and by about 50% in Tx rats. The brown fat thermal response to norepinephrine (NE) infusion was approximately 2-fold increased in the intact rats fed the cafeteria diet. However, in the Tx rats, the brown fat thermal response to NE was blunted regardless of the dietary regimen adopted. In both intact and Tx rats, the cafeteria diet increased total brown fat mitochondria, uncoupling protein percentage, and total brown fat uncoupling protein by about 3-, 2-, and 5-fold, respectively. Serum leptin levels also increased approximately 4-fold in intact rats fed the cafeteria diet. However, in Tx rats, leptin levels did not change significantly during overfeeding. In conclusion, hypothyroidism caused the brown fat to become unresponsive to NE, even after 1 month on the cafeteria diet. However, these rats were able to increase basal metabolic rate and, as assessed by several different parameters, did not gain fat beyond that observed in intact controls kept on a similar overfeeding schedule.     

Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.     

Effect of feeding a high-fat diet during pregnancy on glucose metabolism in the rat

To alter glucose homeostasis in a period of great glucose demand, pregnant rats were submitted to a high-fat diet and compared to virgin rats. In virgin rats, blood glucose, ketone bodies, plasma insulin, and free fatty acids were not affected by the diet consumed. Glucose turnover measured in the postabsorptive period was slightly decreased in virgin rats fed a high-fat diet compared to rats fed a standard diet. Assuming that the glucose turnover rate is representative for the 24-hour average endogenous glucose production, in rats fed a standard diet the daily carbohydrate intake (9.2 +/- 0.7 g/d) exceeded the glucose turnover rate (4 +/- 0.2 g/d) and could meet the glucose requirement. In rats fed a high-fat diet the carbohydrate intake (2.7 +/- 0.2 g/d) was lower than the glucose turnover rate (3.8 +/- 0.2 g/d), which demonstrated the need for an active endogenous glucose production. Blood glucose, ketone bodies, plasma insulin, and free fatty acid concentrations followed the same patterns during pregnancy in rats fed a standard diet compared to rats fed a high-fat diet. The glucose turnover rate in the postabsorptive period was no more decreased by the high-fat diet in pregnant rats compared to virgin rats despite the greater glucose demand. In late pregnancy the glucose turnover rate was increased up to 70%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alcohol consumption aggravates copper deficiency

Male weanling Sprague-Dawley rats were fed a copper-deficient (0.6 microgram Cu/g) diet containing either fructose or starch. Half of the animals fed the starch diet drank a 20% solution of ethanol in water. Ethanol was chosen as an agent to mimic fructose metabolism with the intention that ethanol will exacerbate the signs of copper deficiency and will negate the protective effect of dietary starch. The consumption of a 20% ethanol drink for 6 weeks by copper-deficient rats fed starch resulted in the exacerbation of the deficiency similar to that exerted by fructose. The signs associated with the deficiency in both alcohol and fructose consumption included anemia, heart hypertrophy with gross abnormalities, and mortality. In contrast, none of the copper-deficient control rats that drank water exhibited anemia or heart abnormalities, and none died of the deficiency. In addition, sorbitol pathway in the kidney and liver was stimulated by the consumption of alcohol and fructose. The data support the contention that the combination of certain metabolic pathways of carbohydrate metabolism with copper deficiency are responsible for the exacerbation of the deficiency.     

High fructose diet increases mortality in hypertensive rats compared to a complex carbohydrate or high fat diet

BACKGROUND: Chronic hypertension leads to cardiac hypertrophy, heart failure, and premature death. Little is known about the impact of dietary macronutrient composition on hypertension-induced cardiac hypertrophy and mortality. We investigated the effects of consuming either a high complex carbohydrate diet, a high simple sugar diet, or a high fat diet on cardiac hypertrophy and mortality in hypertensive Dahl salt-sensitive (DSS) rats. METHODS: Rats were assigned to four diets: complex carbohydrate (CC; 70% starch, 10% fat, 20% protein by energy), high fat (FAT; 20% carbohydrates, 60% fat, 20% protein), high fructose (FRU; 70% fructose, 10% fat, 20% protein), and "western" (WES; 35% fructose, 45% fat, 20% protein). Hypertension was initiated by adding 6% NaCl (+S) to the chow of half the animals within each diet (n = 10 to 13/group). Tail cuff blood pressure measurements were assessed after 5 and 11 weeks of treatment, and echocardiography were assessed after 12 weeks of treatment. RESULTS: All rats fed a high salt diet had similar levels of hypertension (CC+S 220 +/-2 mm Hg, FAT+S 221 +/- 3 mm Hg, FRU+S 221 +/- 1 mm Hg, WES+S 226 +/- 3 mm Hg). Echocardiography results show that the addition of salt to FRU resulted in increased regional wall thickness that was not observed in other dietary groups. All rats fed a low salt diet (CC, FAT, FRU, WES) and the FAT+S group survived 90 days. On the other hand, there was 90-day mortality in the WES+S group (18% mortality) and the CC+S group (30% mortality). In addition, FRU+S rats started dying after 45 days of salt feeding, and only 15% survived the full 90 days. CONCLUSIONS: These results demonstrate that a high fructose diet consumed during hypertension increases mortality and left ventricular (LV) wall thickness compared to either a high fat, high starch, or a "western" diet.