Liver fat and plasma ethanol are sharply lower in rats fed ethanol in conjunction with high carbohydrate compared with high fat diets

The effects of high fat and high carbohydrate diets on alcohol metabolism were studied on blood alcohol and liver fat concentration. In Experiment 1, rats consumed an alcohol-containing liquid diet. Blood was collected for ethanol, glucose and lactate analyses and livers were excised for lipid determination. Blood ethanol and liver fat were lower when rats consumed the high carbohydrate diet. Glucose concentrations were lower in rats fed the high fat diet compared with those fed the high carbohydrate diet when ethanol was consumed. In Experiment 2, rats consumed a high fat, ethanol-containing diet for 13 d. Half of the rats were switched to a high carbohydrate, ethanol-containing diet for an additional 11 d. The same analyses were carried out as for Experiment 1. Switching the high fat-fed rats to the high carbohydrate diet reversed the high blood ethanol and high liver fat values, even though the rats consumed significantly more alcohol with the high carbohydrate diet. In Experiment 3 the same high fat and high carbohydrate diets without ethanol were consumed for 2 wk, at which time ethanol was administered acutely, intraperitoneally, at 2 g/kg. Blood was analyzed for ethanol, glucose and lactate 30, 60 and 120 min after injection. Rats fed the high carbohydrate diet had lower blood ethanol but higher lactate at 120 min compared with those fed the high fat diet. The results suggest that the rate of ethanol elimination is slower in rats fed high fat than in those fed high carbohydrate diets, resulting in elevated blood ethanol and liver fat levels for the former.     

Lipoprotein lipase activity in skeletal muscle and brown adipose tissue of pregnant and lactating rats

Changes in lipoprotein lipase (LPL) activity during pregnancy and lactation were followed in skeletal muscles and interscapular brown adipose tissue (BAT) of rats fed two diets differing in energy density (high carbohydrate or high fat). Rats were decapitated after 7, 19 or 21 d of pregnancy or after 3 or 12 d of lactation. Virgin rats and females separated from their litter just after delivery were used as nonpregnant and nonlactating controls, respectively. Blood was collected for determination of plasma glucose, triglycerides (TG) and nonesterified fatty acids (NEFA). Soleus, extensor digitorum longus (EDL), diaphragm and interscapular BAT were rapidly removed and frozen in liquid nitrogen for LPL activity measurement. LPL activity was not significantly higher in muscles and BAT of virgin rats fed the high fat diet than in those of rats fed the high carbohydrate diet. No significant change of skeletal muscle LPL activity was observed during pregnancy, regardless of the diet fed. Although BAT exhibited a transitory hypertrophy during pregnancy, its LPL activity was not significantly altered; during lactation BAT lost weight and its LPL activity dropped sharply when either diet was fed, leaving more TG available for milk production.     

Effects of high-fat diet intake on glucose uptake in central and peripheral tissues of non-obese rats

We previously demonstrated that plasma glucose concentration was higher while plasma insulin concentration was lower in rats fed a high-fat diet. In the present study, we examined the effects of high-fat diet on glucose uptake in central and peripheral tissues in non-obese rats. Forty male Sprague-Dawley rats were fed high- or low-fat diets for 4 wk. Body weight and body fat accumulation were not different between the two diet groups after 4 wk. Glucose uptake in the skeletal muscles and adipose tissues, estimated by the 2-deoxy-D-glucose method, was lower in the rats fed the high-fat diet than that in the rats fed the low-fat diet, whereas uptake in the liver and pancreas did not differ between the two groups. Glucose uptake in the hypothalamus and cortex was higher in the high-fat diet group as compared with that in the low-fat diet group. These results suggest that increased plasma glucose levels in rats fed the high-fat diet were caused by a decrease in glucose uptake in the skeletal muscles and adipose tissues. Reduced plasma insulin level in the high fat diet group with no difference in glucose uptake in the pancreas may be due to increased sympathetic activity in the pancreas resulting from the increased glucose uptake in the brain regions involved in autonomic functions.     

Effect of insulin administration on cardiac glycogen synthase and synthase phosphatase activity in rats fed diets high in protein, fat or carbohydrate

Rats were fed a 70% carbohydrate, 70% protein, 70% fat, or a standard purified diet for 7 d to determine the effect of the diet on heart glycogen synthase response to an acute insulin challenge. Rats fed the high protein or the high fat diets, i.e., the carbohydrate-free diets, exhibited insulin resistance as evidenced by higher plasma glucose levels following insulin administration when compared to rats fed high carbohydrate or standard diet. The diets had no effect on the initial proportion of synthase in the active or I form. Insulin injection resulted in an increase in the proportion of synthase in the active form in rats fed the standard, high carbohydrate or high protein diets, but not in rats fed the high fat diet. Synthase phosphatase activity was similar in rats fed one of the four diets compared to rats fed a nonpurified diet. Thus the lack of synthase response to insulin in fat-fed rats was not due to diminished synthase phosphatase activity. Neither the diets nor insulin administration had any effect on the proportion of phosphorylase in the active or a form. Cardiac glycogen was significantly lower in rats fed the high fat diet than in those fed the standard diet. The latter was a surprising observation since the high fat diet was used to simulate a starved state and cardiac glycogen concentrations increase with starvation.     

Contribution of 500 g naturally labeled 13C dextrin maltose to total carbohydrate utilization and the effect of the antecedent diet, in man

Exogenous carbohydrate oxidation was studied for 24 h in 14 healthy young male volunteers after ingestion of 500 g naturally labeled 13C carbohydrate. Prior to the test, the antecedent diet was high in fat (4 subjects), mixed (4 subjects), or high in carbohydrate (6 subjects). The rate of exogenous carbohydrate oxidation was greater in the high carbohydrate and mixed diet groups than in the high fat group and endogenous carbohydrate continued to contribute to total carbohydrate oxidation for approximately 10 h after ingestion of the carbohydrate load in all groups. After 14 h, 178 +/- 5 g, 241 +/- 11 g and 260 +/- 9 g carbohydrate had been utilized of which 130 +/- 8 g, 155 +/- 6 g and 180 +/- 7 g was of exogenous origin in the high fat, mixed and high carbohydrate groups respectively. At the end of the test, postabsorptive glucose oxidation was of exogenous origin whatever the antecedent diet indicating that much of basal hepatic glucose production was covered by glycogenolysis of recently synthesized labeled glycogen.     

Dietary self-selection patterns of rats with mild diabetes

Rats were allowed a free selection of a diet from among separate sources of protein, fat and carbohydrate or were fed a composite diet formulated to approximate the nutrient composition of a commonly used nonpurified diet. Immediately after streptozotocin injections, diabetic rats displayed polyuria, polydipsia and glycosuria as well as elevated fasting plasma glucose levels and glucose intolerance indicative of mild diabetes. Diabetic rats allowed a free choice tended to consume more protein and consumed significantly less carbohydrate than nondiabetics. This pattern of nutrient choice was associated with a reduction of diabetic signs including reduced polyuria, polydipsia and glycosuria. Diabetic rats permitted to choose their diets were not hyperphagic and maintained a slow but steady rate of body weight gain, accompanied by a sparing of body fat stores. In contrast, diabetic rats consuming the composite diet experienced no improvement in diabetic status; these rats displayed a deterioration of fasting plasma glucose, severe polydipsia, polyuria and glycosuria as well as hyperphagia and wasting of fat stores. These data demonstrate that when mildly diabetic rats are given the opportunity to select their own diets, they choose a diet that leads to improvement of their diabetic status.     

Effect of the alpha-glucosidase inhibitor Bay-O-1248 on the metabolic response of nondiabetic and diabetic rats to a high-carbohydrate diet

The metabolic consequences of the addition of a new alpha-glucosidase inhibitor (BAY-O-1248) to a high carbohydrate diet (67% by calories) in which the carbohydrate comprised equal quantities (50% wt/wt) of wheat starch and sucrose (Diet A) or 100% glucose (Diet B) was studied in diabetic and nondiabetic rats. BAY-O-1248 led to a significant reduction in daily food intake and weight gain in rats fed Diet A but not Diet B. In diabetic rats fed Diet A with BAY-O-1248, daily urinary glucose was significantly diminished (6820 +/- 402 vs 3796 +/- 210 mg), while the postprandial plasma glucose excursions were similar. In nondiabetic rats, the addition of BAY-O-1248 decreased the postprandial plasma glucose level with no change in urine glucose. In summary, addition of an alpha-glucosidase inhibitor to a starch plus sucrose containing diet led to reductions in glycosuria (diabetic rats) and serum glucose levels (normal rats).     

Relation of body energetic status to dietary self-selection in Sprague-Dawley rats

Self-selection from carbohydrate, protein and fat sources including essential micronutrients was studied in male Sprague-Dawley rats that were 4 weeks of age at the beginning of the experiment. During the experimental period of 14 days, the intake of carbohydrate and fat was quite constant, whereas that of protein increased gradually. The mean intake of carbohydrate, protein, and fat was 31.1 +/- 3.5%, 56.1 +/- 4.6%, and 12.8 +/- 2.8% of the total energy intake, respectively. Animals fed on a mixed diet consisting of high sucrose, consumed 65.1% of their daily energy as carbohydrate, 17.6% as protein, and 17.3% as fat. Total energy intake and body weight gain were not significantly different between the rats on self-selection and those fed on the mixed diet. These results indicate that young rats on dietary self-selection were able to gain body weight comparable to that of rats fed on the mixed diet. Body energetic status affected self-selection patterns. In rats fasted for 5 days or fed on a protein-free diet for 21 days, fat intake increased, but protein intake decreased. On the other hand, fat intake decreased in animals given a sucrose diet higher in energy content than the stock diet; these animals exhibited increased accumulation of body energy. These results indicate that dietary self-selection is closely related to nutritional and physiological body requirements.     

Influence of dietary carbohydrate-to-fat ratio on whole body nitrogen retention and body composition in adult rats

Experiments have shown that the amount and source of dietary energy may alter protein metabolism. A high fat diet has resulted in greater nitrogen retention than a high carbohydrate (CHO) diet. To examine this question further, adult rats were fed diets providing ratios of CHO:FAT as a percentage of energy of 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 for 6 wk. Mean energy and protein intakes were 93.0 +/- 0.8 kcal/d and 5.3 +/- 0.1 g/d, respectively. Final body weight was lower in rats fed the high fat diet (CHO:FAT, 0.5) than in rats fed the high carbohydrate diet (CHO:FAT, 3.0) (P less than 0.05), and a linear response was observed over the entire range of treatments (r = 0.92). Rats fed the high fat diet had the highest nitrogen balance; values were significantly (P less than 0.05) different from those of rats fed high carbohydrate diets (CHO:FAT, 2.0 or 2.5) when expressed as mg nitrogen/kcal energy gain. Rats fed the high fat diet had the highest protein gain and the lowest fat gain as a function of energy gain. It is concluded that alterations in nonprotein energy source result in metabolic changes, which may be related to adaptations in energy expenditure and/or protein deposition.     

Self-selection of a high calcium diet by vitamin D-deficient lactating rats increases food consumption and milk production

Lactating and nonlactating rats, both deficient and replete in cholecalciferol, were allowed a free selection among three diets containing 0.47% Ca, 0.3% P (normal Ca, normal P diet); 2.0% Ca, 0.3% P (high Ca diet); and 0.47% Ca, 1.0% P (high P diet). An additional group of vitamin D-deficient lactating rats was fed only the normal Ca, normal P diet. Vitamin D-deficient rats showed a strong selection preference for the high Ca diet but avoided the high P diet, whereas cholecalciferol-replete rats consumed the normal Ca, normal P diet predominantly. Compared to the nonselecting rats, the selection of the high Ca diet by the lactating rats deficient in vitamin D resulted in an increase in plasma calcium levels, hypophosphatemia, a doubling of food consumption, a reduction in maternal body weight loss and a stimulation of milk production as indicated by pup growth. These results demonstrate that vitamin D-deficient rats select a high Ca diet and that the decrease in milk production found in vitamin D deficiency results from a decrease in food consumption and that this anorexia is at least partially dependent on the hypocalcemia normally occurring in vitamin D deficiency.     

Effects of carbohydrate-free diets on the insulin-carbohydrate relationships in rats.

Insulin-carbohydrate relationships were investigated in four groups of young rats fed low protein diets differing in carbohydrate and fat contents: (1) a diet in which the nonprotein energy was provided by fatty acids (FA); (2) a similar diet in which the fatty acids were substituted by neutral fat (NF); (3) FA diet supplemented with glycerol (FA-Glyc); and (4) a carbohydrate-rich diet (HC). Control rats were fed a stock diet. Rats fed the FA diet lost weight, were hypoglycemic and hypoinsulinemic in the fed state and normoglycemic and normoinsulinemic in the fasted state, and had an impaired glucose tolerance and hyperinsulinemia after a glucose load. Liver and muscle glycogen were low in fed rats. Fasting increased glycogen in liver and decreased glycogen in muscle. NF animals gained weight, were hypoglycemic in both fed and fasted states, and their plasma glucose level after an oral glucose load was almost normal. Plasma insulin/glucose ratio, both in fed and fasted states and after a glucose load indicated hyperinsulinism, which was accompanied by obesity. Muscle and liver glycogen were low in fed animals and did not change after a fast. Supplementation of the FA diet with glycerol (FA-Glyc) abolished weight loss and fasting hyperglycemia and normalized plasma glucose and insulin response to a glucose load. Rats fed the HC diet had an improved glucose tolerance and an increased sensitivity to insulin. Liver glycogen was high in the fed state and normal in the fasted state, whereas muscle glycogen was normal in both nutritional states.     

Lipid composition of liver plasma membranes isolated from rats fed a high glucose or a high fat diet.

Several plasma membrane associated functions have been shown to differ in rats fed a high lard, carbohydrate free diet (L rats) from those observed in preparations from rats fed a high glucose, fat free diet (G rats). To explore the possibility that differences in the lipid components of the plasma membranes might contribute to these functional changes, groups of rats were fed each diet for 5 days and the lipids of their plasma membranes were separated and analyzed. The major differences found were a greater cholesterol content in the plasma membranes from L rats compared to those of G rats (12.2 +/- 2.20 versus 7.8 +/- 1.40 mg/100 mg membrane protein) and more than twice as much phosphatidyl serine and phosphadidyl inositol in the plasma membranes of the former group. Of several variations in fatty acid distribution found in the phospholipid and neutral lipid fractions, the most notable quantitatively were an increase in phospholipid oleic acid (18:1) and a decrease in phospholipid stearic acid (18:0) in L rat plasma membranes. Whether these changes are related to altered membrane function is not known.     

Retrospective analysis of the impact of a low glycaemic index diet on hospital stay following coronary artery bypass grafting: a hypothesis

OBJECTIVE: Glucose tolerance and insulin resistance influence medical outcome in subjects with coronary artery disease, these metabolic parameters also influence general perioperative surgical outcome. We hypothesize that glucose tolerance and insulin resistance can be favourably modified by reducing the glycaemic index of the diet. DESIGN: The present study is a retrospective analysis of a low and high glycaemic index diet on glucose tolerance, insulin resistance and perioperative outcome, as assessed by the length of hospital stay following coronary artery bypass surgery. Thirty-five adults awaiting bypass surgery were randomized, for the 4 weeks prior to surgery, to either a low glycaemic index diet (17 subjects) or high glycaemic index diet (18 subjects). Glucose and insulin responses during a 75 g oral glucose tolerance test were assessed before and after dietary intervention and insulin-mediated glucose uptake was assessed in isolated adipocytes obtained at surgery. RESULTS: The patients who consumed a low glycaemic diet had improved glucose tolerance and significantly greater in vitro adipocyte insulin sensitivity at the time of surgery compared with the high glycaemic diet group (78.87 +/- 10.64% versus 41.11 +/- 7%, respectively). The total length of stay in the patients on the low glycaemic diet was less than patients consuming the high glycaemic diet (7.06 +/- 0.38 days versus 9.53 +/- 1.44 days, P < 0.5). CONCLUSION: This study provides further support that carbohydrate and fat metabolism influence cardiac outcome and provides new evidence that dietary modification prior to coronary artery bypass surgery can shorten hospital stay.     

Effects of high sucrose or starch-bran diets on glucose and lipid metabolism of normal and diabetic rats.

Normal and streptozotocin-diabetic rats were fed a low carbohydrate diet or one of two high carbohydrate diets (sucrose or starch-bran). High carbohydrate diets were associated with slightly higher plasma glucose levels in both control and diabetic rats. However, glucose tolerance tests were not altered by the diets in either the control or diabetic rats. Plasma and liver triglyceride values for control and diabetic rats fed the high sucrose diet were similar to those of rats fed the low carbohydrate diet. The starch-bran diet was associated with lower plasma and liver triglyceride values in both control and diabetic rats. Plasma triglyceride values of diabetic rats fed the high sucrose diet or the low carbohydrate diet were significantly higher than values of control rats fed the same diets. On the other hand, plasma triglyceride values of diabetic rats fed the starch-bran diet were similar to values for control rats fed the same diet. These studies suggest that a high carbohydrate diet containing starch and wheat bran is associated with a reduction in plasma triglyceride values in both normal and diabetic rats. Liver glycolytic enzyme activities were significantly lower in diabetic rats than in control rats in all three dietary groups.     

Replacement of digestible wheat starch by resistant cornstarch alters splanchnic metabolism in rats.

Splanchnic metabolism was investigated in rats fed either a diet containing highly digestible wheat starch (DS diet) or amylase-resistant cornstarch (RS diet). In rats fed the latter diet, there was a considerable enlargement of the cecum and an increase in the production and absorption of volatile fatty acids (VFA), chiefly acetic and propionic acids. As a result, the major substrates absorbed from the digestive tract were glucose in rats fed the DS diet and both glucose and VFA in rats fed the RS diet. The liver removed about one-third of the absorbed glucose in rats fed the DS diet, whereas there was a slight release of glucose by the liver in rats fed the RS diet. Plasma insulin was higher in rats fed the DS diet, and there were smaller fluctuations of plasma insulin and liver glycogen between the fed and postabsorptive periods in rats adapted to the RS diet. In these animals, propionate was the major VFA taken up by the liver and approximately 50% of absorbed acetate was also removed by the liver. During the postabsorptive period, there was still a substantial contribution of VFA, especially propionate, to liver metabolism. A depressive effect of the RS diet on plasma triglycerides, cholesterol and free fatty acids was observed only during the postabsorptive period. Replacement of a large part of absorbed glucose by VFA apparently allows time for absorption of energy fuels to be extended and dampens the fluctuations of glucose metabolism during the light: dark cycle.     

Tocotrienols Reverse Cardiovascular,Metabolic and Liver Changes in High Carbohydrate,High Fat Diet-Fed Rats

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.     

The redox state and the concentration of ketone bodies in tissues of rats fed carbohydrate free diets.

The effect of carbohydrate free-low protein diets on the redox potential and ketone body concentrations in liver, muscle, and blood was investigated. Two carbohydrate free diets were fed: 1) A diet in which all the non-protein energy was provided by fatty acids (FA); 2) A similar diet in which the fatty acids were substituted by neutral fat (NF). A carbohydrate rich diet (HC) was fed for comparison. The redox potentials in cytoplasma and mitochondria were calculated from the relative concentrations of the [lactate]:[pyruvate] and [beta-hydroxy-butyrate]:[acetoacetate] couples respectively. In fed rats the cytoplasmic redox potential in liver was much higher in FA than in NF rats, but in fasted NF rats it increased markedly and equaled that of FA rats. In liver mitochondria the redox potential was lower in fed FA than in fed NF rats, while after a 24 hour fast it increased in FA rats and decreased in NF rats. Total ketone body concentrations were high in fed NF rats and increased further in fasted rats, however, in FA rats the high concentrations in the fed state decreased after the short fast. The changes of total ketone-bodies in blood and muscle followed those in liver in both fed and fasted states.     

Dietary fat saturation affects hepatocyte insulin binding and glucose metabolism in BHE rats

The influence of feeding 6% hydrogenated coconut oil, corn oil or menhaden oil on hepatocyte insulin binding, receptor number and glucose use was studied. Hepatocytes isolated from rats fed menhaden oil had a significantly greater affinity for insulin than hepatocytes from rats fed hydrogenated coconut oil. Glucose use was not influenced by diet; uniformly labeled glucose was metabolized to CO2 or to lipid similarly in cells isolated from rats fed the three oils. Thus, dietary fat type in a low fat diet influenced events at the plasma membrane without influencing intracellular events.     

Effects of intravenous nutrition on lipoprotein metabolism, body composition, weight gain and uremic state in experimental uremia in rats

The effect on serum lipids, lipoprotein fractions, body composition, weight gain and uremic state of including fat in intravenous nutrition was evaluated in rats with chronic uremia. Uremic rats were given high energy (1385 kJ.kg body weight-1.day-1), low nitrogen (0.6 g N.kg body weight-1.day-1) total parenteral nutrition (TPN) for 12 d with either glucose or glucose plus 30% lipids (Intralipid) as the energy source. Additional uremic and nonuremic groups were fed a standard diet orally. During TPN, serum triglyceride and cholesterol levels were slightly higher in rats fed lipid-based TPN compared to those administered glucose-based TPN or fed the oral diet; but there were no differences 8 h after feeding. The serum lipoprotein fractions showed accumulation of lipids in LDL resulting from the lipid-based TPN but no differences in VLDL. In orally fed uremic rats, more lipids were found in HDL than in the TPN-treated rats. The fractional clearance of the fat emulsion was normal and independent of the nutrition composition. Uremic rats administered lipid-based TPN for 21 d had the same weight gain as orally fed, nonuremic control rats (23 +/- 3 vs. 22 +/- 2%); glucose-based TPN did not support normal growth (10 +/- 1%). Uremic rats fed orally did not grow and retained significantly more body water than TPN-fed uremic rats. In uremic animals, lipid-based TPN also was associated with normal body composition despite significantly lower levels of carnitine in plasma, skeletal muscle and heart tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipoprotein lipid and protein responses to dietary fat and diabetes in rats

Dietary and insulin-deficiency types of hyperlipidemia were compared in adult normal and streptozotocin-induced diabetic male breeder rats. High beef tallow, high corn oil or low fat diets (BT, CO and LF, respectively) were fed ad libitum for 2 months. Glucose and insulin were measured in plasma and total cholesterol, free cholesterol, cholesteryl ester, triglycerides and apoproteins in very low density, low density and high density lipoproteins (VLDL, LDL and HDL, respectively). Diet did not affect plasma glucose or insulin levels. LDL-triglycerides were higher in BT and diabetic than in CO and LF rats. HDL-free cholesterol levels were higher in CO- and LF-than in BT-fed rats. Diabetes resulted in a decrease in HDL-cholesterol. Diabetic animals had higher HDL-apoA-I (apolipoprotein A-I) levels than did CO- and LF- but not BT-fed rats. VLDL-triglycerides were higher in diabetic than in normal rats, with no dietary differences in normal rats. In LDL, apoB levels were lower and apoE levels were higher in LF-fed rats than in animals fed high fat diets. Diabetes resulted in an increase in LDL-apoB but a decrease in LDL-apoE. HDL-apoE levels were higher, although HDL-apoA-I levels were lower in LF than in high fat-fed rats. The results related to lipoprotein composition supported the hypothesis that excess intake of a diet high in saturated fat may contribute to a metabolic pattern that resembles that of a diabetic state.