High-fat High-carbohydrate Diet Research Articles

Protective effect of metformin in CD1 mice placed on a high carbohydrate–high fat diet

A high carbohydrate–high fat (HC–HF) diet-associated with hyperinsulinemia has been previously reported to induce accelerated growth of prostate cancer in a xenograft model. High energy supply and insulin/insulin growth factor-1 axis are two of the mechanisms proposed. We hypothesize that metformin may have a protective effect against prostate cancer progression by affecting metabolisms associated with high energy intake. In the present study, animals were randomized into five groups, receiving a HC–HF diet with 50, 100, or 250 mg/kg body weight (mg/kg) metformin in drinking water, a standard diet or HC–HF diet alone. Animals on the HC–HF diet developed obesity and insulin resistance. They had significantly higher body weight, fasting blood glucose at an upper level of normal range, higher insulin secretion and utilization, and fatty degeneration of the liver. Metformin at the doses employed significantly reduced food and water consumption; however, only a dose of 250 mg/kg showed a significant reduction in body weight gain and suppression of gluconeogenesis as well remarkably reduced insulin secretion. There was no observed metformin-related hepato-toxicity in any of the groups. In summary, metformin at various doses exhibits protective effects on the metabolic disorder caused by the HC–HF diet with the most effective protection at a dose of 250 mg/kg. These effects may explain its translational role relating to its anti-neoplastic potential.

Olive Leaf Extract Attenuates Cardiac, Hepatic, and Metabolic Changes in High Carbohydrate–, High Fat–Fed Rats1–3

Olive oil, an important component of the Mediterranean diet, produces cardioprotective effects, probably due to both oleic acid and the polyphenols such as oleuropein and hydroxytyrosol. Our aim in this study was to assess whether a polyphenol-enriched extract from the leaves of Olea europaea L. with oleuropein as the major component attenuated the cardiovascular, hepatic, and metabolic signs of a high-carbohydrate, high-fat (HCHF) diet (carbohydrate, 52%; fat, 24%, 25% fructose in drinking water) in rats. Male Wistar rats were fed either a cornstarch diet (CS) or a HCHF diet for a total of 16 wk. Diets of the treatment groups [CS+olive leaf extract (OLE) and HCHF+OLE] were supplemented with 3% OLE after 8 wk of being fed their respective CS or HCHF diets for a further 8 wk. After 16 wk, HCHF rats developed signs of metabolic syndrome, including elevated abdominal and hepatic fat deposition, collagen deposition in heart and liver, cardiac stiffness, and oxidative stress markers (plasma malondialdehyde and uric acid concentrations), with diminished aortic ring reactivity, abnormal plasma lipid profile, impaired glucose tolerance, and hypertension. Compared with HCHF rats, those in the HCHF+OLE group had improved or normalized cardiovascular, hepatic, and metabolic signs with the exception of elevated blood pressure. These results strongly suggest that an OLE containing polyphenols such as oleuropein and hydroxytyrosol reverses the chronic inflammation and oxidative stress that induces the cardiovascular, hepatic, and metabolic symptoms in this rat model of diet-induced obesity and diabetes without changing blood pressure.

Association of Diet-Induced Hyperinsulinemia With Accelerated Growth of Prostate Cancer (LNCaP) Xenografts

Prior research suggested that energy balance and fat intake influence prostate cancer progression, but the influence of dietary carbohydrate on prostate cancer progression has not been well characterized. We hypothesized that hyperinsulinemia resulting from high intake of refined carbohydrates would lead to more rapid growth of tumors in the murine LNCaP xenograft model of prostate cancer. Athymic mice were injected subcutaneously with LNCaP human prostate cancer cells and, when tumors were palpable, were randomly assigned (n = 20 per group) to high carbohydrate-high fat or low carbohydrate-high fat diets. Body weight and tumor volume were measured weekly. After 9 weeks, serum levels of insulin and insulin-like growth factor 1 (IGF-1) were measured by enzyme immunoassay. AKT activation and the levels of the insulin receptor in tumor cells were determined by immunoblotting. The in vitro growth response of LNCaP cells to serum from mice in the two treatment groups was measured based on tetrazolium compound reduction. All statistical tests were two-sided. After 9 weeks on the experimental diets, mice on the high carbohydrate-high fat diet were heavier (mean body weight of mice on the high carbohydrate-high fat diet = 34 g versus 29.1 g on the low carbohydrate-high fat diet, difference = 4.9 g, 95% CI = 3.8 to 6.0 g; P = .003), experienced increased tumor growth (mean tumor volume in mice on high carbohydrate-high fat diet = 1695 versus 980 mm3 on low carbohydrate-high fat diet, difference = 715 mm3, 95% CI = 608 to 822 mm3; P<.001), and experienced a statistically significant increase in serum insulin and IGF-1 levels. Tumors from mice on the high carbohydrate-high fat diet had higher levels of activated AKT and modestly higher insulin receptor levels than tumors from mice on the low carbohydrate-high fat diet. Serum from mice on the high carbohydrate-high fat diet was more mitogenic for LNCaP cells in vitro than serum from mice fed the low carbohydrate-high fat diet. A diet high in refined carbohydrates is associated with increased tumor growth and with activation of signaling pathways distal to the insulin receptor in a murine model of prostate cancer.

Effects of High Carbohydrate Low Fat Nigerian-Like Diet on Biochemical Indices in Rabbits

The effects of a low carbohydrate high fat Nigerian like diet on lipoprotein levels, serum electrolytes, liver and renal functions were investigated. The diet consist of 28% carbohydrate and 35% fat as percentage of total energy in a wholly compounded form. Twelve rabbits were randomly divided into two groups. The groups were: Group I that was fed the control diet and the second group II were fed with the low carbohydrate high fat diet. At the end of eight weeks, biochemical analyses were done on blood samples of the animals. There were significant (p<0.05) decrease in weight for the experimental animals when compared with the control group. Total protein, albumin and globulin did not change significantly (p<0.05), for the rabbits fed on the low carbohydrate high fat diet. Aspartate Transaminase (AST) and Alanine Transaminase (ALT) levels increased significantly (p<0.05) while Alkaline Phosphatase (ALP) levels decreased significantly (p<0.05). The bilirubin level for rabbits on the experimental diet did not change significantly (p<0.05). Serum electrolyte concentrations showed no significant change in sodium, potassium, chloride and bicarbonate ions when compared with control. Creatinine and urea values showed no significant (p<0.05) changes. Total Cholesterol levels were significantly (p<0.05) reduced in the experimental diet. The lipoprotein fractions showed significant increases (p<0.05) in High Density Lipoprotein (HDL) and Triacylglycerol (TAG) levels when compared with controls. Low Density Lipoprotein (LDL)-Cholesterol did not change significantly (p<0.05). The results showed that the Low Carbohydrate High Fat (LCHF) Nigerianlike diet promotes hypertriglyceridemia and weight loss. This could also increase the risk of ischemic heart disease.

Caloric intake and dietary fat to carbohydrate ratio influence body weight accretion and adiposity in rats fed by total enteral nutrition

Consumption of high energy high-fat diets leads to weight gain and adiposity in rodents. However the relative roles of higher caloric intake vs. increased dietary fat remain unclear. Low carbohydrate high fat diets, like the Atkins diet, claim to promote weight loss. We employed a total enteral nutrition model to evaluate roles of caloric intake and dietary fat to carbohydrate ratio in mediating weight gain. Female Sprague-Dawley rats were fed either 187 kcal/kg3/4/d (normal calorie, NC, NRC requirements) or 220 kcal/kg3/4/d (overfed 15% excess calories/d, high calorie, HC) via intragastric infusion. NC and HC diets were either low fat (LF, 5% calories from fat, corn oil) or high fat (HF, 45% calories from fat, ~20-fold higher fat/carbohydrate than LF). LF and HF diets were isocaloric. Protein (casein) was 20% of caloric intake and carbohydrate calories contributed to 75% and 35% in the LF and HF diets, respectively. A separate group of rats were fed regular rodent chow (ad libitum). After 6 weeks of infusion of diets, body weights (BW) of rats fed NC-HF matched ad lib fed controls. HC-HF rats showed significantly higher (152%) BW compared to NC-HF and ad lib fed controls. However, both NC and HC rats fed LF diets consistently showed ~20% higher BW compared to rats fed HF diets. Consistent with BW data, body composition as assessed by Echo MRI revealed higher fat mass/BW in rats fed HC diets. Greater fat mass/BW was also observed in NC-LF rats as compared to NC-HF fed rats. Analysis of oral glucose tolerance tests to evaluate insulin resistance as a function of caloric and diet fat intake is ongoing. Supported in part by ARS CRIS #6251-51000-003-065

The role of an experimental model as a predictor of morbility in children

Children nutritional assessment by a food record remains controversial. Anthropometric and biochemical measurements are highly accurate. However, an animal model may predict and identify individuals at risk. We observed that some children despite no having evidence of inadequacies in body proportions, body composition, biochemical profile or dietary intake, showed a significant reduction in serum IGF I levels. In order to assess these discrepancies, a children population (aged 2 to 8) of the Southern of Argentina (Comodoro Rivadavia, province of Chubut) was studied. Anthropometric measurements, biochemical determinations and habitual food ingestion were collected. From 91 children attending a food program, 8% achieved low weights (W=-1.93 ± 0.42) and heights (H=-1.87 ± 0.24) (OMS, 2001), with appropriate WHZ (-1.14 ± 0.54); % body fat within normal range, and an adequate intake of energy, protein, heme iron, calcium and vitamin A according RDA, but serum IGF I decreased significantly (129.4 ± 83.9 ng/ml, p<0.05). After comparing to our rat experimental model of low fat-high carbohydrate diet, we did realize that short stature and low IGF I were common among individuals with nutritional dwarfing (ND). Issue that provides an explanation for individuals who have normal WHZ, but growing differently than expected. Unfortunately, the animal model revealed alterations in bone and mineral metabolisms that could be prevented in children following a diet intervention program. UBACyT O004 and O003.

Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk

BackgroundIt is speculated that high saturated fat very low carbohydrate diets (VLCARB) have adverse effects on cardiovascular risk but evidence for this in controlled studies is lacking. The objective of this study was to compare, under isocaloric conditions, the effects of a VLCARB to 2 low saturated fat high carbohydrate diets on body composition and cardiovascular risk.MethodsEighty three subjects, 48 ± 8 y, total cholesterol 5.9 ± 1.0 mmol/L, BMI 33 ± 3 kg/m2 were randomly allocated to one of 3 isocaloric weight loss diets (6 MJ) for 8 weeks and on the same diets in energy balance for 4 weeks: Very Low Fat (VLF) (CHO:Fat:Protein; %SF = 70:10:20; 3%), High Unsaturated Fat (HUF) = (50:30:20; 6%), VLCARB (4:61:35; 20%)ResultsPercent fat mass loss was not different between diets VLCARB -4.5 ± 0.5, VLF-4.0 ± 0.5, HUF -4.4 ± 0.6 kg). Lean mass loss was 32-31% on VLCARB and VLF compared to HUF (21%) (P < 0.05). LDL-C increased significantly only on VLCARB by 7% (p < 0.001 compared with the other diets) but apoB was unchanged on this diet and HDL-C increased relative to the other 2 diets. Triacylglycerol was lowered by 0.73 ± 0.12 mmol/L on VLCARB compared to -0.15 ± 0.07 mmol/L on HUF and -0.06 ± 0.13 mmol/L on VLF (P < 0.001). Plasma homocysteine increased 6.6% only on VLCARB (P = 0.026). VLCARB lowered fasting insulin 33% compared to a 19% fall on HUF and no change on VLF (P < 0.001). The VLCARB meal also provoked significantly lower post prandial glucose and insulin responses than the VLF and HUF meals. All diets decreased fasting glucose, blood pressure and CRP (P < 0.05).ConclusionIsocaloric VLCARB results in similar fat loss than diets low in saturated fat, but are more effective in improving triacylglycerols, HDL-C, fasting and post prandial glucose and insulin concentrations. VLCARB may be useful in the short-term management of subjects with insulin resistance and hypertriacylglycerolemia.

Arguments for a lower carbohydrate-higher fat diet in patients with a short small bowel

Short small bowel patients suffer from malabsorption due to a strongly reduced small bowel surface. These patients usually get a high caloric high carbohydrate-low fat diet at oral or enteral feeding. At several points our studies demonstrate that the effect of this formula is doubtful. In these patients the intestinal flora has strongly been changed and even become characteristic due to abundant presence of lactobacilli (up to nearly 100%). In many patients with a high carbohydrate-low fat diet these bacteria both produce massive amounts of d-lactic acid and gaseous CO2, and they destroy the primary bile acids that are necessary for uptake of lipids. Thus, they cause (i) an increased risk of D-lactic acidosis and D-lactic acid-associated encephalopathy, (ii) flatulence, abdominal pain and non-infectious diarrhoea, and (iii) low uptake of fat and lipophilic vitamins. It is argued that by gradually converting the diet to a low carbohydrate-high fat diet growth of the characteristic lactobacilli can be strongly reduced and so also the mentioned inconveniences.

Determining the relationship between dietary carbohydrate intake and insulin resistance

Insulin resistance underlies type 2 diabetes, CVD and the metabolic syndrome, driven by changes in diet, lifestyle, energy over-consumption and obesity. Nutritional recommendations for insulin resistance remain an area of controversy, particularly the quantity and types of dietary carbohydrate. The present review gives an overview of insulin resistance, its relationship to impaired insulin secretion and the metabolic syndrome, research methodologies used to measure insulin action and the epidemiological and intervention studies on the relationship between dietary carbohydrate and insulin resistance. Epidemiological studies provide little evidence to suggest that total dietary carbohydrate predicts risk of type 2 diabetes, and high-carbohydrate, high-fibre diets with low-glycaemic index (GI) may even contribute to diabetes prevention. Despite inherent limitations associated with techniques used to measure insulin resistance and dietary assessment, most intervention studies reveal an increase in glucose tolerance or insulin sensitivity with high-carbohydrate, low-fat diets in non-diabetic and diabetic individuals. When energy is restricted the source or reduced content of carbohydrate does not appear to be as important as fat for body weight. Thus, low energy intake is key to weight loss and augmentation of insulin sensitivity. Given this, widespread adoption of popular low-carbohydrate high-fat diets highlights the necessity to evaluate dietary interventions regarding safety and metabolic effects. While current evidence supports FAO/WHO recommendations to maintain a high-carbohydrate diet with low-GI foods, the relationships between carbohydrate and insulin sensitivity remains an important research area. Emerging technologies should further enhance understanding of gene-diet interactions in insulin resistance, providing useful information for future nutrition policy decisions.

Pengaruh pemberian diet rendah karbohidrat tinggi lemak terhadap penurunan CO2 darah dan perbaikan respirasi pada pasien penyakit paru obstruktif kronik di Rumah Sakit Immanuel Bandung

Background: Lung diseases are one of the main health problems in Indonesia. Among the lung diseases, Chronic Obstructive Pulmonary Disease (COPD) is the 7th leading causes of death in Indonesia. The prevalence COPD tends to increase due to increasing smoking habit, industrialization, air pollution, and more elderly people. Diet regulation for COPD patients were mainly for energy consumption, and accurate proportion of carbohydrate and fat. Excessive carbohydrate intake will increase blood CO2.Objective: To evaluate the influence of low carbohydrate and high fat diet on the decrease of CO2 concentration and improving respiration in acute exacerbation of COPD.Methods: This is an experiment study, with pre and posttest design. The subjects were COPD patients who hospitalized due to acute exacerbation. The subjects must be conscious, no left heart failure, no coronary heart disease, no acute respiratory failure that need ventilator and hospitalized for minimum 7 days and could take oral diet.Results: Women, younger, and no smoking COPD patients had decreased blood CO2 offer low carbohydrate high fatty diet. All patients with this diet experience had improvement in their respiratory symptoms.Conclusion: Low carbohydrate high fat diet decreases blood CO2 in new acute exacerbation of COPD patients, no smoking women and younger patients. However, this diet improved respiratory symptoms for all patients who receive it.

The case for low carbohydrate diets in diabetes management

A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (<30 g/day) cannot be recommended for a diabetic population at this time without further study. On the other hand, the dire objections continually raised in the literature appear to have very little scientific basis. Whereas it is traditional to say that more work needs to be done, the same is true of the assumed standard low fat diets which have an ambiguous record at best. We see current trends in the national dietary recommendations as a positive sign and an appropriate move in the right direction.

Fat intake and energy-balance effects

This paper focuses on the effects of dietary fats or fatty acids on key targets of metabolic intermediates for body-weight control, i.e. satiety, thermogenesis, fat oxidation and body composition. With respect to sensory satiety, it appeared, e.g. that linoleic acid tasters showed a different mechanism for meal termination than non-tasters did. They stopped eating linoleic acid containing food based upon satiety, whereas the non-tasters stopped eating based upon the change in pleasantness of taste. Moreover, in the normal range of body mass index, an inverse relationship was shown between % ‘tasters’ and BMI. In a high fat diet vs. a low fat high protein high carbohydrate diet, metabolic satiety appeared to be continuously lower and correlated positively to diet-induced energy expenditure. However, with respect to the intermeal interval, satiety appeared to be more sustained following a high fat vs. a high CHO preload, resulting in a lower meal frequency. Covert fat replacement during breakfast by sucrose polyester was successful in combination with dietary restraint, yet overt fat replacement in snacks was successful in the dietary-unrestrained subjects, i.e. those who habitually ate snacks. With respect to fat oxidation, from a respiration-chamber experiment on the effects of diacylglycerol compared (DG) to triacylglycerol (TG) intake, it was concluded that consumption of DG increased fat oxidation and β-hydroxy-butyrate levels, but did not affect energy metabolism or triacylglycerol level. Parameters of appetite were all lowered by DG compared to TG. With respect to body composition, the effects of 13 weeks CLA supplementation in overweight subjects during weight regain were assessed. Although CLA did not affect %body-weight regain, the regain of fat-free mass was increased by CLA, independently of %body-weight regain and physical activity, and as a consequence resting metabolic rate was increased. At the same time, appetite was reduced and satiety and fullness were increased. In conclusion, we also determined bright sports with respect to fat intake.

Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1.

Increased plasminogen activator inhibitor 1 (PAI-1) has been linked to not only thrombosis and fibrosis but also to obesity and insulin resistance. Increased PAI-1 levels have been presumed to be consequent to obesity. We investigated the interrelationships of PAI-1, obesity, and insulin resistance in a high-fat/high-carbohydrate (HF) diet-induced obesity model in wild-type (WT) and PAI-1-deficient mice (PAI-1(-/-)). Obesity and insulin resistance developing in WT mice on an HF diet were completely prevented in mice lacking PAI-1. PAI-1(-/-) mice on an HF diet had increased resting metabolic rates and total energy expenditure compared with WT mice, along with a marked increase in uncoupling protein 3 mRNA expression in skeletal muscle, likely mechanisms contributing to the prevention of obesity. In addition, insulin sensitivity was enhanced significantly in PAI-1(-/-) mice on an HF diet, as shown by euglycemic-hyperinsulinemic clamp studies. Peroxisome proliferator-activated receptor (PPAR)-gamma and adiponectin mRNA, key control molecules in lipid metabolism and insulin sensitivity, were maintained in response to an HF diet in white adipose tissue in PAI-1(-/-) mice, contrasting with downregulation in WT mice. This maintenance of PPAR-gamma and adiponectin may also contribute to the observed maintenance of body weight and insulin sensitivity in PAI-1(-/-) mice. Treatment in WT mice on an HF diet with the angiotensin type 1 receptor antagonist to downregulate PAI-1 indeed inhibited PAI-1 increases and ameliorated diet-induced obesity, hyperglycemia, and hyperinsulinemia. PAI-1 deficiency also enhanced basal and insulin-stimulated glucose uptake in adipose cells in vitro. Our data suggest that PAI-1 may not merely increase in response to obesity and insulin resistance, but may have a direct causal role in obesity and insulin resistance. Inhibition of PAI-1 might provide a novel anti-obesity and anti-insulin resistance treatment.

Ethanol consumption decreases the synthesis of the mannose 6-phosphate/insulin-like growth factor II receptor but does not decrease its messenger RNA

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR) is a protein that facilitates the transport of acid hydrolases into the lysosome. We have shown that chronic ethanol consumption lowers the M6P/IGF-IIR content in rat hepatocytes. Here, we determined the steady-state level of mRNA encoding M6P/IGF-IIR, as well as the rate of receptor synthesis, to ascertain whether the ethanol-elicited reduction in receptor protein content is related to changes in either or both of these parameters. Rats were pair-fed the normal carbohydrate (NC) or low carbohydrate high-fat (LC) liquid diets containing either ethanol or isocaloric maltose-dextrin for 7–8 weeks. RNA was isolated from hepatocytes and from whole livers of these animals and subjected to reverse transcription–polymerase chain reaction (RT–PCR) to determine the mRNA levels encoding M6P/IGF-IIR. Hepatocytes isolated from these animals were also radiolabeled with Pro-mix l-[ 35 S ] in vitro cell labeling mix to measure incorporation into total cellular protein and the immunoprecipitated M6P/IGF-IIR protein. The steady-state levels of M6P/IGF-IIR mRNA in both hepatocytes and whole livers from ethanol-fed rats were the same as those from their respective controls regardless of whether they were fed the NC or the LC diets. Hepatocytes from ethanol-fed rats showed a 36% lower rate of total protein synthesis and an even greater reduction (70%) in receptor synthesis. When the relative rate of receptor synthesis was calculated, hepatocytes from ethanol-fed rats had a 53% lower relative rate of receptor synthesis compared with controls. Autoradiographic analysis of the immunoprecipitated receptor protein from ethanol-fed rats also indicated a 79% decline in the total M6P/IGF-IIR protein synthetic rate compared with pair-fed controls. We conclude that the ethanol-elicited reduction of M6P/IGF-IIR content was, in part, related to a concomitant reduction of receptor protein synthesis but not to a decline in its mRNA level. Thus, the ethanol-elicited decline in receptor protein synthesis may be due to defective M6P/IGF-IIR mRNA translation.

Metabolic Syndrome

Case Presentation: E.C. is a 53-year-old postmenopausal female, referred for treatment of hypertension, with a family history of type 2 diabetes, hypertension, and coronary heart disease (CHD). Until learning that her blood pressure was “too high” during a routine physical examination, she felt well, and her postmenopausal symptoms had responded to hormone replacement therapy. She was not overweight (her body mass index [BMI] was 23.7 kg/m2), and the only abnormality on physical examination was a blood pressure of 145/95 RAR. Laboratory results revealed a normal blood count and urinalysis, with the following fasting plasma concentrations of relevant metabolic variables (in mg/dL): glucose 102, triglycerides (TG) 238, low-density lipoprotein cholesterol (LDL-C) 147, and high-density lipoprotein cholesterol (HDL-C) 52. E.C. is hypertensive and hypertriglyceridemic and at increased risk for CHD. Less obvious is that these metabolic abnormalities are highly likely to be the manifestations of a more fundamental defect—resistance to insulin-mediated glucose disposal and compensatory hyperinsulinemia, changes that greatly increase CHD risk.1,2⇓ The importance of insulin resistance as a CHD risk factor was first explicated in 1998, and the cluster of abnormalities likely to appear as manifestations of the defect in insulin action designated as syndrome X.1 Support for this notion has grown almost as fast as the names used to describe the phenomenon. The Adult Treatment Panel III (ATP III) has recently3 recognized the importance as CHD risk factors of a “constellation of lipid and nonlipid risk factors of metabolic origin,” designated this cluster of abnormalities as “the metabolic syndrome,” and indicated that “this syndrome is closely linked to insulin resistance.” Table 1 lists the criteria the ATP III stipulated be used to diagnose the metabolic syndrome, and a recent report4 has applied these criteria to the database of the Third National Health and Nutrition …

Interaction of physical activity and diet: implications for lipoprotein metabolism.

To consider how physical activity interacts with diet to modify lipoprotein metabolism and comment on implications for human health. An overview of lipoprotein metabolism is followed by a summary of the main effects of physical activity on lipoprotein metabolism. Interactions with dietary practice and the disposition of dietary lipid are reviewed, with comment on links with body fatness. Literature is reviewed in relation to the risk of atherosclerotic disease. Although some data are presented on athletic groups, evidence relating to individuals with normal physical activity habits is mainly discussed. Physical inactivity is a risk factor for cardiovascular disease and one mechanism may involve changes to lipoprotein metabolism. The consensus is that aerobic activity involving an expenditure of > or = 8 MJ week(-1) results in an increase in HDL cholesterol and probably decreases in fasting triacylglycerol. These changes Occur despite the spontaneous increase in the proportion of dietary energy from carbohydrate which accompanies increased exercise. For this reason, exercise may be a means of reducing the hypertriglyceridaemic and HDL-lowering effects of low fat (high carbohydrate) diets. Decreases in total and low density lipoprotein cholesterol are sometimes, but not always, reported in sedentary individuals beginning exercise. One mechanism linking all these changes may be alterations to the dynamics of triacylglycerol-rich particles, particularly in the fed state. The expenditure of considerable amounts of energy through regular, frequent physical activity increases the turnover of lipid substrates, with effects on their transport and disposition which may reduce the progression of atherosclerosis.

Body fat and exercise endurance in trained rats adapted to a high-fat and/or high-carbohydrate diet.

To study how diet composition affects exercise endurance and body composition, 48 male Sprague-Dawley rats were treadmill trained for 8 wk while consuming either a high-fat (F) diet or high-carbohydrate (C) diet. The diets were switched for one-half the number of rats in each group 3 days before the animals were killed, during which feeding time the rats did not exercise. One-half of rats receiving each of the four diet combinations were taken at rest (R) or exhaustion (E), resulting in eight groups: CCR, CFR, FFR, FCR, CCE CFE, FFE, and FCE. An analysis of variance revealed that resting glycogen in the FCR group was enhanced in muscle (19-33%) and liver (23%) compared with controls. Each F group's exercise time to exhaustion [CFE, 322.9 +/- 25.0; FFE, 356.8 +/- 37.8; FCE, 467.0 +/- 32.6 (SE) min] was different (P < 0.05) from control (CCE, 257.5 +/- 29.2 min). Postexercise glycogen was equivalent among all dietary groups, were muscle triglycerides. The FF and FC groups had higher 3-hydroxyacyl-CoA dehydrogenase activity in soleus muscle than either CC or CF animals. After training, body weights were similar between the two dietary groups; however, percent body fat was 17% greater after the F diet, even though F diet animals voluntarily consumed 12% less energy than did C diet animals. These data suggest that exercise endurance time is optimized in trained rats that receive a carbohydrate load after adaptation to a F diet. However, despite intense exercise training, the F diet promotes body fat deposition, and the health consequences of following such a regimen are still unknown.

Effect of Enterostatin on the Feeding Responses to Galanin and NPY

We have investigated the possibility that enterostatin may inhibit the intake of dietary fat by inhibiting either galanin or NPY-induced feeding pathways. Rats, adapted to either high fat (HF) or low fat-high carbohydrate (HC) diets and fitted with third ventricular cannulas were used to study the effects of intracerebroventricular (i.c.v.) enterostatin on i.c.v. NPY and galanin induced feeding responses in satiated rats. An equimolar dose of enterostatin (0.1 nmoles) inhibited, while a tenfold excess of enterostatin abolished the feeding response to galanin in rats adapted to a HF diet. The galanin stimulation of food intake was reduced in rats adapted to the HC diet and this response was less sensitive to inhibition by enterostatin. Enterostatin had no inhibitory effects on NPY-induced feeding in rats adapted to the HC diet and only a small inhibitory effect, at tenfold molar excess, in rats adapted to the HF diet. The ability of enterostatin to bind to galanin or NPY Y-1 receptors was investigated in ligand binding studies. Enterostatin failed to displace 125I-galanin or 125I-PYY from specific binding sites in rat forebrain homogenates or SK-N-MC cells respectively. The data provide support for the hypothesis that enterostatin specifically inhibits a galanin-responsive fat intake system, but indicate that this effect is not modulated by direct interaction with either galanin or NPY-Y1 receptors.

Hypertension in CB57BL/6J mouse model of non-insulin-dependent diabetes mellitus.

The C57BL/6J (BL/6) mouse develops non-insulin-dependent diabetes mellitus (NIDDM) when fed a high fat-high simple carbohydrate (HFHSC) diet, whereas A/J mice do not. The purpose of the study was to determine whether hypertension occurred with NIDDM and whether it was sustained by sympathetic nervous system (SNS) hyperactivity. After 3 mo on an HFHSC diet with a low Na content (0.06%), awake, tail-cuff systolic blood pressure (BP) increased 20% above the control diet in BL/6 (138 +/- 3 vs. 115 +/- 4) but not in A/J (115 +/- 6 vs. 113 +/- 2 mmHg) mice. On a normal Na (0.4%)-HFHSC diet, BL/6 mice had a higher BP than on 0.06% Na (149 +/- 3 at 3 mo, 162 +/- 6 at 4.5 mo). After 1 mo on the 0.06% Na-HFHSC diet, direct BP of anesthetized BL/6 mice was 18% higher than control. The hypotensive response to interruption of SNS activity by ganglionic blockade (chlorisondamine) increased in the BL/6 mice (50%), whereas the heart rate response increased in both strains (20-30%). Analysis of variance (ANOVA) on glucose detected significant effects of strain and diet and a strain x diet interaction (P = 0.0007). At 1 or 3 mo, HFHSC-fed BL/6 mice were hyperglycemic (> 11 mM) compared with diet or strain controls. The ANOVA on insulin detected strain and diet effects but not a strain x diet interaction (P = 0.3). HFHSC increased insulin above the control of 140-160 pM in A/J and BL/6 strain (20-70% at 1 mo, 400% at 3 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphometric analysis of the endocrine pancreas in streptozotocin-diabetic rats kept on different dietary regimens.

The effects of different diets on the endocrine pancreas of streptozotocin-diabetic rats were investigated by morphometry. Three dietary regimens were used over a period of 43 weeks: standard diet (SD), low carbohydrate-high protein diet (LC-HP), and low carbohydrate-high fat diet (LC-HF). Nondiabetic controls received standard diet. Volume density of the total endocrine tissue was significantly reduced in streptozotocin-diabetic rats kept on standard diet as compared to control rats. This reduction of endocrine tissue was significantly less in rats kept on LC-HP diet, whereas diabetic rats kept on LC-HF did not differ from diabetic rats on standard diet. In streptozotocin-diabetic rats volume density of B cells was drastically reduced, whereas volume densities of A, D and PP cells did not differ from nondiabetic controls. This decrease of B cells was partially prevented by LC-HP diet, but not by LC-HF diet. In nondiabetic control rats as in diabetic rats on standard diet most of the islets of Langerhans sized 500-6000 microns2. In contrast, diabetic rats on LC-HP diet revealed more endocrine tissue sized from 50 to 560 microns2 consisting of two to four endocrine cells, single cells, and small islets. The results suggest that LC-HP diet may initiate reparation processes in the endocrine pancreas of streptozotocin-diabetic rats.