Dietary carbohydrate level determines the effect of long-term ethanol ingestion on rat pancreatic amylase content

We studied the effects of long-term ethanol feeding on pancreatic amylase content in the rat. Because the level of pancreatic amylase depends on the carbohydrate content in the diet, the effects of ethanol ingestion were investigated at different levels of dietary carbohydrate, with fat providing the balance of calories. Animals were maintained on these diets for 3 weeks. In control animals, a reduction in carbohydrate from 47% to 11% of total calories lowered pancreatic amylase content by 60% (from 76.1 +/- 7 U/mg protein to 30.6 U/mg protein). However, in rats that consumed 11% of total calories as carbohydrate, long-term ethanol ingestion (36% of total calories) lowered the amylase content by a further 60% (from 30.6 U/mg protein to 11.8 U/mg protein). By contrast, when the dietary carbohydrate level was maintained at a high (40%) level, long-term ethanol ingestion slightly increased pancreatic amylase content. Pancreatic lipase was not affected by long-term ethanol ingestion at either low (6%) or high (35%) levels of fat. The reduction in the level of amylase caused by ethanol feeding with a low dietary carbohydrate intake was not associated with changes in the fasting blood levels of glucose, insulin, or glucagon. Long-term ethanol ingestion did not lead to morphologic changes in the acini or in the size, shape, or number of granules, as observed by light and electron microscopy. These results suggest that long-term ethanol ingestion has differential effects on pancreatic amylase, depending on the level of carbohydrate in the diet.     

一日三餐高脂低碳水化合物摄入对健康成人糖耐量的影响

目的观察葡萄糖耐量（OGTT）前1天高脂低碳水化合物撮入（热量相同但碳水化合物撮入减少,脂肪撮入增加）对健康成人糖耐量的影响,从而进一步确定是否OGTT前1天高脂低碳水化合物（HF）撮入导致糖耐量减低（IGT）的误诊。方法30例男性健康成人随机分为两组（HF组和对照组）进行交叉试验;分别于OGTT前1天早、中、晚餐时撮入热量相同的HF或对照配餐;次日清晨行75g OGTT;分别测定血糖、胰岛素、游离脂肪酸、甘油三酯厦胆固醇浓度;2次OGTT间隔1周。结果OGTT前1天HF使糖负荷后30、60、120分钟血糖分别升高33％、51％厦42％,胰岛素分泌指数（△I／△G）降低50％,空腹血浆游离脂肪酸（FFA）浓度上升100％,使30％健康成人被误诊为IGT。结论即使总热量撮入相同,OGTT前1天HF引起健康成人空腹血浆游离脂肪酸水平升高,抑制早期胰岛素分泌,引起糖负荷后血糖的升高,导致IGT的误诊。     

Urinary citrate excretion in patients with renal stone: roles of leucocyte ATP citrate lyase activity and potassium salts therapy

BACKGROUND: Hypocitraturia is a major metabolic abnormality in rural Northeast Thais with renal stones. These people also have low serum and urinary potassium and consume a high carbohydrate and low fat diet, which together might influence the intracellular metabolism and urinary excretion of citrate. METHODS: In Study A, we measured plasma and urinary chemistries and assayed leucocyte ATP citrate lyase (ACL) activity in 30 normal urban control subjects (Group A1) and 30 rural renal stone patients (Group A2) in Northeast Thailand. Some of the subjects from both groups were also used to evaluate the intake of carbohydrate, protein and fat. In Study B, we examined the effects of potassium salts therapy with another group of 30 rural renal stone patients: Group B1 (n = 15) treated with potassium chloride and Group B2 (n = 15) with potassium-sodium citrate (with an aim to achieve 42 mEq potassium, 21 mEq sodium and 62 mEq citrate per day for 1 month). RESULTS: In Study A, the leucocyte ACL activity of Group A1 was much lower than that of Group A2 (3.2 +/- 0.7 vs. 9.3 +/- 3.8 micromol acetylhydroxamate/mg protein/30 min, p < 0.0001). The plasma potassium, urinary excretions of potassium and citrate in Group A1 were higher than in Group A2. When data of the two groups were combined, urinary citrate excretion was inversely correlated with leucocyte ACL activity (r = 0.6783, p < 0.001). While the dietary protein intake did not differ between Groups A1 and A2, the carbohydrate intake by Group A1 was significantly lower (65.2 +/- 7.9% vs. 83.1 +/- 2.9%, p < 0.01) and fat higher (21.0 +/- 6.4% vs. 6.2 +/- 4.1%, p < 0.002) than Group A2. After treatment with potassium chloride (Group B1), only the potassium was increased (p < 0.001), while those treated with potassium-sodium citrate (Group B2) experienced a significant increase in urinary pH (p < 0.002), potassium (p < 0.001) and citrate (p < 0.001), and a decrease in leucocyte ACL activity (p < 0.001). CONCLUSIONS: Compared to normal subjects, renal stone patients have low urinary citrate excretion with high leucocyte ACL activity. In Northeast Thailand, low potassium status and a high carbohydrate and low fat diet may cause the increased ACL activity. However, hypokaliuria, hypocitraturia and high leucocyte ACL activity can be corrected by potassium-sodium citrate salt therapy.     

High protein diet complements resin therapy of familial hypercholesterolemia.

The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia.     

DIET AND TISSUE GROWTH : I. THE REGENERATION OF LIVER TISSUE ON VARIOUS ADEQUATE DIETS.

1. The toxicity of chloroform varies according to the diets used in these experiments in the following order of decreasing susceptibility of the animals: high fat > standard > high carbohydrate > high protein diets. 2. On the high fat and high carbohydrate diets there may be a more or less marked proliferation of the endothelium and the connective tissue stroma in the necrotic area producing in some instances scars resembling the picture of an early cirrhosis. 3. On the diets studied, standard, high carbohydrate, high protein, and high fat, the most active and rapid repair is observed on the standard balanced diet. On the high fat diet the reparative process is definitely delayed in comparison with the others. There are only slight differences between the high carbohydrate and high protein diets which suggest but do not conclusively show a more rapid repair with the latter diet.     

慢性阻塞性肺疾病缓解期患者膳食营养调查

目的：研究慢性阻塞性肺疾病（ＣＯＰＤ）缓解期患者膳食营养状况。方法：采用３天记录加询问法进行膳食调查。资料输入微机,采用笔者编制的“慢性阻塞性肺疾病患者营养状况和饮食指导软件”进行数据处理。结果：ＣＯＰＤ缓解期患者膳食中总热量、蛋白质、碳水化合物、锌、钙、硒、ＶｉｔＡ、ＶｉｔＢ１、ＶｉｔＢ２、ＶｉｔＣ摄入不足,其中低体重组较体重正常组摄入不足更为明显。三大产能营养素供能比例不够合理,碳水化合物比例过高（６０％）。三餐热量分配早餐偏低（２４％）,晚餐偏高（３９％）。结论：饮食摄入不足是ＣＯＰＤ缓解期患者营养不良的重要原因之一,应引起重视。     

Dietary fat selectively alters transport properties of rat jejunum.

The influence of dietary fatty acid composition on intestinal active and passive transport function, brush border membrane composition, and morphology was examined in rats. Animals fed a semisynthetic diet high in saturated fatty acids demonstrated enhanced in vitro jejunal uptake of decanoic, dodecanoic, palmitic, stearic, and linoleic acid, as well as cholesterol and chenodeoxycholic and taurochenodeoxycholic acid, as compared with uptake in animals fed a semisynthetic diet high in polyunsaturated fatty acids but equivalent in total content of fat and other nutrients, or as compared with Purina chow. Feeding the saturated fatty acid diet was also associated with reduced jejunal uptake of a range of concentrations of glucose, enhanced ileal uptake of leucine, unchanged uptake of galactose, and lower uptake of decanol. The semisynthetic diets did not alter brush border membrane protein, sucrase or alkaline phosphatase activities, cholesterol, or total phospholipids, although the percentage of jejunal amine phospholipids was higher than in rats fed chow. The morphologic differences between the jejunum and ileum were abolished in animals fed the high polyunsaturated fatty acid diet; in rats fed the high saturated fatty acid diet, there was reduced mean ileal villus height, width, thickness, surface area, cell size, and villus density, as well as reduced mucosal surface area. The changes in jejunal transport were not correlated with the alterations in morphology, unstirred layer resistance, food intake, or body weight gain. It is proposed that small changes in the percentage of total dietary lipids composed of essential and nonessential fatty acids (without concurrent alterations in dietary total fat, carbohydrate, or protein) influence active and passive intestinal transport processes in the rat.     

Outpatient management of diabetes mellitus with patient education to increase dietary carbohydrate and fiber

The impact of patient education on dietary fiber intake, diabetes control, and serum lipids was examined in patients with non-insulin-dependent diabetes mellitus. Customary outpatient personnel and procedures were used to teach three diet plans: the American Diabetes Association (ADA) diet, the ADA diet modified to increase high-fiber, high-carbohydrate foods (IF), and the IF diet supplemented with oat bran (IFOB). A control group was instructed on foot care to provide teaching visits. Fifty-two patients were recruited from an outpatient clinic and studied over a 6-wk period. Subjects were of low socioeconomic status and had completed a mean of 8.3 yr of education. Patients instructed to increase their intake of high-fiber foods reported a doubling of fiber intake and tolerated the diets well. Increased fiber and carbohydrate intake and decreased fat intake were associated with reductions in fasting plasma glucose levels. Increased fiber intake was also associated with reductions in total serum cholesterol and high-density lipoprotein cholesterol levels. Changes in fiber, carbohydrate, and fat intake were unrelated to changes in weight, serum insulin levels, or hemoglobin A1c levels over the study period.     

Glucose Metabolism and the Response to Insulin by Human Adipose Tissue in Spontaneous and Experimental Obesity: EFFECTS OF DIETARY COMPOSITION AND ADIPOSE CELL SIZE

[1-(14)C]glucose oxidation to CO(2) and conversion into glyceride by adipose tissue from nonobese and obese subjects has been studied in vitro in the presence of varying medium glucose and insulin concentrations as functions of adipose cell size, the composition of the diet, and antecedent weight gain or loss.Increasing medium glucose concentrations enhance the incorporation of glucose carbons by human adipose tissue into CO(2) and glyceride-glycerol. Insulin further stimulates the conversion of glucose carbons into CO(2), but not into glyceride-glycerol. Incorporation of [1-(14)C]glucose into glyceride-fatty acids by these tissues could not be demonstrated under any of the conditions tested.Both adipose cell size and dietary composition influence the in vitro metabolism of glucose in, and the response to insulin by, human adipose tissue. During periods of ingestion of weight-maintenance isocaloric diets of similar carbohydrate, fat, and protein composition, increasing adipose cell size is associated with (a) unchanging rates of glucose oxidation and increasing rates of glucose carbon incorporation into glyceride-glycerol in the absence of insulin, but (b) decreasing stimulation of glucose oxidation by insulin. On the other hand, when cell size is kept constant, increasing dietary carbohydrate intake is associated with an increased basal rate of glucose metabolism and response to insulin by both small and large adipose cells. Thus, the rate of glucose oxidation and the magnitude of the insulin response of large adipose cells from individuals ingesting a high carbohydrate diet may be similar to or greater than that in smaller cells from individuals ingesting an isocaloric lower carbohydrate diet.The alterations in basal glucose metabolism and insulin response observed in adipose tissue from patients with spontaneous obesity are reproduced by weight gain induced experimentally in nonobese volunteers; these metabolic changes are reversible with weight loss. The relationships among adipose cell size, dietary composition, and the metabolism of adipose tissue are similar in spontaneous and in experimental obesity.     

EXPERIMENTAL PRODUCTION OF PYLOROSPASM AND GASTRIC RETENTION IN RATS

1. A method was found whereby the development of gastric retention could be studied in intact animals without the necessity of recourse to the use of x-rays. 2. Gastric retention was found to develop as a result of protein restriction in 7 out of 10 rats studied. Such retention could again be cleared up with protein realimentation or by allowing the animals free choice of protein, fat and carbohydrate. 3. A diet high in protein following periods of undernutrition or prolonged protein restriction usually gave rise to a transient gastric retention. 4. Diets with a solution of 25 per cent or more of alcohol added promptly gave rise to gastric retention in rats even when the protein content of the diet was adequate. 5. Evidence is given indicating that the gastric retention which occurred in this study involved more or less pylorospasm and the possible influence of mechanical and chemical irritation and of changes in gastric mucin and bile flow upon the development of pylorospasm are discussed. 6. Spira''s theory that fat in the diet gives rise to pylorospasm and ulceration is not supported by the results of our experiments.     

A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities, as well as on the ability of plasma to stimulate cellular cholesterol efflux. Twelve male type 1 diabetic patients with plasma cholesterol >5.0 mmol/L were studied while consuming their usual diet and after 6 weeks of a low-fat, low-cholesterol diet. Pre beta-HDL formation was measured using crossed immuno-electrophoresis. Plasma LCAT, CETP and PLTP activities were assayed by exogenous substrate methods. The ability of plasma to promote cellular cholesterol efflux out of Fu5AH rat hepatoma cells and out of human skin fibroblasts was also determined. Saturated fat intake was lowered (p = 0.001) due to replacement with carbohydrates, while mono- and polyunsaturated fat intake remained unchanged. Cholesterol intake decreased as well (p = 0.003). The changes in plasma total cholesterol, very low and low-density lipoprotein (VLDL+LDL) cholesterol, HDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, plasma LCAT activity and PLTP activity were not significant. Plasma CETP activity (p = 0.008) and pre beta-HDL formation (p = 0.008) decreased. The ability of plasma to promote cholesterol efflux out of fibroblasts and Fu5AH cells remained unchanged. Reduction in dietary saturated fat and cholesterol intake does not adversely affect cellular cholesterol efflux to plasma from type 1 diabetic patients, despite a drop in pre beta-HDL formation.     

Effect of protein on sympathetic nervous system activity in the rat. Evidence for nutrient-specific responses.

Increased energy intake activates the sympathetic nervous system (SNS) in animals and man. While dietary carbohydrate and fat stimulate, the impact of dietary protein on the SNS is not well defined. The present studies examine the effect of protein ingestion on sympathetic function based upon the measurement of [3H]norepinephrine (NE) turnover in heart and interscapular brown adipose tissue (IBAT) as the index of SNS activity. In these experiments, animals were pair-fed mixtures of laboratory chow and refined preparations of casein, sucrose, and lard to permit comparisons among nutrients with total energy intake held constant or with additional energy provided in the form of a single nutrient. After 5 d of eating a 2:1 mixture of chow and either casein or sucrose cardiac, [3H]NE turnover was less (P less than 0.005) in casein-fed rats (6.4%/h and 28.9 ng NE/h) than in animals given sucrose (11.2%/h and 46.5 ng NE/h). Similar results were obtained in IBAT and in experiments using 1:1 mixtures of chow and casein/sucrose. Casein-fed animals also displayed slower rates of NE turnover than lard-fed rats in both heart (7.8%/h vs. 13.2, P less than 0.001) and IBAT (7.0%/h vs. 12.8, P less than 0.01). Addition of casein (50% increase in energy intake) to a fixed chow ration raised NE turnover slightly, but not significantly, in heart (an average increase of 15% in six experiments). Thus, in distinction to SNS activation seen with dietary carbohydrate or fat, the SNS response to dietary protein is minimal in both heart and IBAT, indicating that the effect of increased energy intake on the SNS is dependent upon diet composition.     

Short-term effects of varying glucose intake on body composition of malnourished adult patients

Changes in weight and body content of protein, carbohydrate, fat, total body water, intra- and extracellular water, Na, and K were estimated from balance measurements in malnourished adult patients receiving total parenteral nutrition for consecutive 8-day periods, containing either a low or high carbohydrate content. Total caloric intake was 65% of energy expenditure on the low intake and 119% on the high intake, with a difference of 54% due entirely to carbohydrate. Although there are many assumptions and approximations necessarily involved in multiple balance studies, the accuracy is sufficient to produce useful information in short-term studies of this type. It is particularly useful in looking at differences between diets, since most of the methodologic errors cancel out. The effect of the increased glucose intake was to significantly increase storage, or decrease loss, of fat, carbohydrate, protein, intracellular water, and K. Changes in Na and extracellular water varied widely among patients, but were not affected by the increase in glucose. Most of the increase in K content (83%) was associated with glycogen deposition; a much smaller amount (17%) was associated with protein deposition. Thus, the ratio of K/N deposited (15 mEq of K:1 g of N) was very different from the 3:1 ratio seen in most tissues. Changes in any one constituent of body cell mass may not, therefore, be good indicators of changes in another. Since protein is the most important active component of body cell mass, changes in body cell mass components other than N should be interpreted with caution when used as indices of nutritional therapy.     

Dietary protein suppresses feedback control of glomerular filtration in rats.

We have examined the possibility that changes in glomerular filtration rate (GFR) after changes in dietary protein intake may depend on altered function of the tubuloglomerular (TG) feedback system. We studied male Sprague-Dawley rats after dietary pretreatment for 9.6 +/- 3.6 (SD) d with isocaloric diets containing either 6% or 40% casein. We found that GFR in rats fed the high protein diet was 24-29% higher than in rats fed the low protein diet. Simultaneous measurements of single nephron GFR (SNGFR) in the distal tubule were 6.3 nl/min or 21% higher in the rats fed the high protein diet whereas proximally measured SNGFR was not statistically different in the two groups. The higher distally measured SNGFR of rats receiving the high protein diet was associated with a 4.2 nl/min or 50% smaller suppression of SNGFR by TG feedback (-4.3 vs. -8.5 nl/min, P less than 0.001). Loop perfusion experiments demonstrated that in rats fed the high protein diet the TG feedback mechanism was less sensitive than in rats fed the low protein diet. The TG feedback response in rats fed the low protein diet, as assessed by reductions in stop-flow pressure and SNGFR, was half-maximal at flows of 14-15 nl/min. In contrast, the TG feedback response in rats fed the high protein diet was half-maximal at 22-24 nl/min. Maximal suppression of stop-flow pressure and SNGFR and the slope of the TG feedback response to increasing loop flow rates were not different in the two groups. We conclude that the sensing mechanism of the TG feedback system is rendered less responsive by a high protein intake, and that this change permits GFR to increase.     

Effects of low-protein diet on experimental diabetic nephropathy in the rat

To evaluate the role of glomerular hyperfiltration in the development and progression of diabetic nephropathy, we performed clearance and histopathologic studies in 24 rats with streptozocin-induced diabetes after 3 months of diets with different protein compositions. Calcium phosphate was added to an 8% protein diet in group I (nine rats), and calcium carbonate to a 24% protein diet in group II (nine rats) to equalize calcium and phosphate contents in these diets. Group I and II rats also received small doses of insulin to reduce the excessive hyperglycemia induced by the high sucrose content of the diets. In group III, six rats given an 8% protein diet, no calcium, phosphate, or insulin was added. In groups I and III, low dietary protein significantly reduced glomerular filtration rate and renal plasma flow per gram of kidney weight as compared with rates observed in group II rats with a higher protein intake. Features of diabetic glomerulopathy including mesangial hypercellularity and mesangial matrix expansion were also significantly milder in the groups with a low protein diet. On the other hand, medullary calcification and interstitial changes were most prominent in group I, given calcium phosphate supplement; the increase in the kidney weight was greater in groups I and II, which received insulin, than in group III, which did not. It was concluded that low protein diet significantly ameliorates diabetic glomerulopathy but that supplementation with inorganic phosphate in an amount equal to organic phosphate contained in the higher protein diet causes medullary calcification and interstitial nephritis. Also, administration of suboptimal doses of insulin in diabetic animals greatly enhances renal growth, more than that induced by diabetes alone.     

High-carbohydrate, high-fiber diet. Is it practical and effective in treating hyperlipidemia?

More than one half of middle-aged Americans have undesirably high serum lipid levels. Diets high in fiber and carbohydrate and low in fat reduce serum lipid levels two to four times more than the widely recognized American Heart Association diet. High intake of soluble fiber is especially effective for lowering serum cholesterol levels; alcohol restriction and weight reduction help lower serum triglycerides. High-carbohydrate, high-fiber diets combined with regular exercise and healthy life-style hold great potential to reduce hyperlipidemia and the incidence of coronary artery disease in the United States.     

Protein losing enteropathy associated with Nippostrongylus brasiliensis infestation and its impact on albumin homoeostasis in rats fed two levels of dietary protein

Alterations in plasma albumin concentration and gastrointestinal permeability have been investigated in rats infected with the nematode Nippostrongylus brasiliensis and fed adequate or low protein diets. Infection caused only minor changes in growth and food consumption of well nourished rats but resulted in significant reductions in those fed the low protein diet. Animals in both dietary groups were able to mount an immune response beyond day 10 post-infection (p.i.) which caused expulsion of the parasites, but this was less effective in rats fed the low protein food. Uninfected rats fed the low protein diet had significantly lower plasma albumin concentrations than their well nourished counterparts. Animals of both dietary groups showed a progressive reduction in plasma albumin concentration as the infection developed but values returned towards normal as the parasites were expelled. The reduction in plasma albumin concentration was closely associated with increases in gastrointestinal leakage of plasma protein but losses were far greater in the protein deficiency animals. Beyond day 10 p.i. protein loss decreased in both dietary groups and by day 21 p.i. had returned to normal in well nourished animals but not those fed the low protein diet. Intestinal permeability measured by the lactulose:mannitol ratio technique gave similar results to the protein loss data. Permeability increased as the infection progressed then fell as the worms were expelled but remained above control values in infected protein deficient animals. Overall, animals fed the low protein diet were more severely affected by the parasite than were their well fed counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms for Development of Diabetic Hypertriglyceridemia in Streptozotocin-Treated Rats EFFECT OF DIET AND DURATION OF INSULIN DEFICIENCY

A combined ultrastructural and functional approach was employed to define the effects of duration of diabetes and of diet on various aspects of lipid metabolism in rats with severe streptozotocin (SZ)-induced insulin deficiency. Plasma triglyceride (TG) levels rose to a mean of 479 mg/100 ml 24 h after SZ administration in rats eating a fat-free, high carbohydrate diet as compared to a mean of 324 mg/100 ml in rats eating a high fat diet. These changes were associated with a commensurate increase in hepatocyte Golgi very low density lipoprotein (VLDL) content, but only a small increase in estimates of VLDL-TG secretion rate (post-Triton WR 1339 increment in plasma TG level). Although these findings are consistent with the thesis that VLDL-TG synthesis and secretion are increased 24 h after administration of SZ, it seemed unlikely that the observed increase in VLDL-TG secretion could entirely account for the severity of the hypertriglyceridemia. Thus, although lipoprotein removal rate was not measured directly, it was necessary to postulate that a defect in VLDL-TG removal was also present at this stage.Hypertriglyceridemia was still present 7 days later, only in this instance plasma TG levels were higher in rats eating the high fat diet (a mean of 589 mg/100 ml, as compared to 263 mg/100 ml). Rats with diabetes of 7-day duration had a 50% decrease in both TG entry rate and hepatocyte Golgi complex VLDL content, irrespective of diet. Thus, there was no evidence of increased VLDL-TG secretion in chronic insulin deficiency. In this instance, although not assessed directly, it was necessary to postulate that the hypertriglyceridemia in chronically insulin-deficient rats is due entirely to a defect in lipoprotein removal, involving both dietary and endogenous fat.     

Increasing the fat-to-carbohydrate ratio in a high-fat diet prevents the development of obesity but not a prediabetic state in rats

Metabolic disorders induced by high-fat feeding in rodents evoke some, if not all, of the features of human metabolic syndrome. The occurrence and severity of metabolic disorders, however, varies according to rodent species, and even strain, as well as the diet. Therefore, in the present study, we investigated the long-term obesogenic and diabetogenic effects of three high-fat diets differing by their fat/carbohydrate ratios. Sprague-Dawley rats were fed a control high-carbohydrate and low-fat diet [HCD; 3:16:6 ratio of fat/carbohydrate/protein; 15.48 kJ/g (3.7 kcal/g)], a high-fat and medium-carbohydrate diet [HFD1; 53:30:17 ratio of fat/carbohydrate/protein; 19.66 kJ/g (4.7 kcal/g)], a very-high-fat and low-carbohydrate diet [HFD2; 67:9:24 ratio of fat/carbohydrate/protein; 21.76 kJ/g (5.2 kcal/g)] or a very-high-fat and carbohydrate-free diet [HFD3; 75:0:25 ratio of fat/carbohydrate/protein; 24.69 kJ/g (5.9 kcal/g)] for 10 weeks. Compared with the control diet (HCD), rats fed with high-fat combined with more (HFD1) or less (HFD2) carbohydrate exhibited higher BMI (body mass index; +13 and +10% respectively; P<0.05) and abdominal fat (+70% in both HFD1 and HFD2; P<0.05), higher plasma leptin (+130 and +135% respectively; P<0.05), lower plasma adiponectin levels (-23 and -30% respectively; P<0.05) and impaired glucose tolerance. Only the HFD1 group had insulin resistance. By contrast, a very-high-fat diet devoid of carbohydrate (HFD3) led to impaired glucose tolerance, insulin resistance and hypoadiponectinaemia (-50%; P<0.05), whereas BMI, adiposity and plasma leptin did not differ from respective values in animals fed the control diet. We conclude that increasing the fat-to-carbohydrate ratio to the uppermost (i.e. carbohydrate-free) in a high-fat diet prevents the development of obesity, but not the prediabetic state (i.e. altered glucose tolerance and insulin sensitivity).