Differential effects of high-carbohydrate and high-fat diets on hepatic lipogenesis in rats

Purpose

Hepatic fatty acid synthesis is influenced by several nutritional and hormonal factors. In this study, we have investigated the effects of distinct experimental diets enriched in carbohydrate or in fat on hepatic lipogenesis.

Methods

Male Wistar rats were divided into four groups and fed distinct experimental diets enriched in carbohydrates (70 % w/w) or in fat (20 and 35 % w/w). Activity and expression of the mitochondrial citrate carrier and of the cytosolic enzymes acetyl-CoA carboxylase and fatty acid synthetase were analyzed through the study with assessments at 0, 1, 2, 4, and 6 weeks. Liver lipids and plasma levels of lipids, glucose, and insulin were assayed in parallel.

Results

Whereas the high-carbohydrate diet moderately stimulated hepatic lipogenesis, a strong inhibition of this anabolic pathway was found in animals fed high-fat diets. This inhibition was time-dependent and concentration-dependent. Moreover, whereas the high-carbohydrate diet induced an increase in plasma triglycerides, the high-fat diets determined an accumulation of triglycerides in liver. An increase in the plasmatic levels of glucose and insulin was observed in all cases.

Conclusions

The excess of sucrose in the diet is converted into fat that is distributed by bloodstream in the organism in the form of circulating triglycerides. On the other hand, a high amount of dietary fat caused a strong inhibition of lipogenesis and a concomitant increase in the level of hepatic lipids, thereby highlighting, in these conditions, the role of liver as a reservoir of exogenous fat.     

Differential effects of high-carbohydrate and high-fat diet composition on metabolic control and insulin resistance in normal rats

The macronutrient component of diets is critical for metabolic control and insulin action. The aim of this study was to compare the effects of high fat diets (HFDs) vs. high carbohydrate diets (HCDs) on metabolic control and insulin resistance in Wistar rats. Thirty animals divided into five groups (n = 6) were fed: (1) Control diet (CD); (2) High-saturated fat diet (HSFD); (3) High-unsaturated fat diet (HUFD); (4) High-digestible starch diet, (HDSD); and (5) High-resistant starch diet (HRSD) during eight weeks. HFDs and HCDs reduced weight gain in comparison with CD, however no statistical significance was reached. Calorie intake was similar in both HFDs and CD, but rats receiving HCDs showed higher calorie consumption than other groups, (p < 0.01). HRSD showed the lowest levels of serum and hepatic lipids. The HUFD induced the lowest fasting glycemia levels and HOMA-IR values. The HDSD group exhibited the highest insulin resistance and hepatic cholesterol content. In conclusion, HUFD exhibited the most beneficial effects on glycemic control meanwhile HRSD induced the highest reduction on lipid content and did not modify insulin sensitivity. In both groups, HFDs and HCDs, the diet constituents were more important factors than caloric intake for metabolic disturbance and insulin resistance.     

Lipid and lipid-free total parenteral nutrition: differential effects on macrophage phagocytosis in rats

Lipid emulsions provided with total parenteral nutrition (TPN) have been associated with mononuclear phagocytic system functional changes. The aim of the present investigation was to assess the influence of TPN with added lipid emulsions on macrophage (M phi) phagocytosis. Wistar rats (n = 70) with external jugular vein cannulation were randomized into seven groups. The rats received an oral diet or six different isocaloric (1.16 kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30% non-protein calories) TPN regimens: (a) an oral diet with intravenous infusion of saline (OS); (b) non-lipid TPN (glucose); (c) TPN with 10% long chain triacylglycerol emulsions (LCT); (d) TPN with 90% LCT and 10% fish oil (FO) emulsion; (e) TPN with 50% LCT and 50% FO; (f) TPN with 10% lipid emulsion with 50% medium chain triacylglycerol (MCT) and 50% LCT; and (g) TPN with 45% MCT, 45% LCT, and 10% FO. After 96 h of TPN or saline infusion, colloidal carbon (Pelikan, Germany) was injected intravenously at 1.0 mL/kg body weight, and the rats were killed after 3 h. Liver, spleen, and lung were weighed and prepared by immunohistochemistry analyses with the HAM-56 anti-M phi antibody. Under light microscopy, the total M phi number (MT) and the colloidal carbon phagocytic M phi number (MP) were established, and the phagocytic index was calculated as MP/MT x 100. There were no statistical (P < 0.05) differences in liver, spleen, or lung weights among the seven groups in comparison with the OS group. Non-lipid TPN inhibited spleen and lung M phi phagocytosis when compared with the OS and lipid-TPN groups. Lipid TPN supplemented with fish oil emulsion increased total liver and lung M phi number and phagocytosis. These results indicate that TPN supplemented with fish oil increases M phi phagocytosis in rats.     

门静脉与外周静脉途径肠外营养代谢效应的比较

12例大肠癌手术患者随机分成二组,6例术中留置门脉导管.术后第2日行肠外营养5日,每日提供6.2gN及1340keal非蛋白热卡,糖/脂热卡比为62%:38%,营养液经门静脉(门脉组)或外周静脉(对照组)输入.血浆白蛋白、三酸甘油酯、胆固醇、胆红素、转氨酶及血糖在营养前后均行监测,未见明显改变.营养结束时累积氮平衡门脉组与对照组分别为-0.13±2.40与-5.72±2.98gN/5d(P<0.01),提示经门静脉PN能更好地维持氮平衡.     

Effects of parenteral nutrition supplemented with alanyl-glutamine on nutrition status in rats

BACKGROUND: Glutamine, a nonessential amino acid, has received increasing attention because it becomes essential during stress and catabolic conditions. Many investigations have shown that during severe stress, the consumption of glutamine exceeds glutamine synthesis, resulting in depletion of glutamine stores. The aim of this study was to evaluate the effects of supplementing parenteral diets with a glutamine-containing dipeptide, L-alanyl-L-glutamine, on rat nutrition status. METHODS: Male Wistar rats were used. Animals (n = 36) were centrally catheterized and randomly assigned to 1 of the following groups based on method of parenteral nutrition (PN): control group with oral nutrition and IV infusion of a saline solution; standard parenteral nutrition (SPN) group; or alanyl-glutamine-supplemented PN (ALA-GLN PN) group (20 g/L). Parenteral nutrition was isocaloric and isonitrogenous. Infusions were administered at a rate of 2.0 mL/h over 5 days. Nutrition status was assessed by body weight change, plasma proteins, accumulated urinary creatinine, and nitrogen balance. RESULTS: Accumulated urinary creatinine increased significantly after day 4 in the ALA-GLN PN group, compared with the SPN group and the controls. Body weight change significantly differed on day 5 between the ALA-GLN PN and SPN groups. After 3 days, nitrogen balance was significantly lower and nitrogen retention higher in the ALA-GLN PN group when compared with the SPN group. Albumin and transferrin concentrations decreased significantly in the SPN group, but did not differ from the controls in the ALA-GLN PN group. CONCLUSIONS: Weight, plasma proteins, urinary accumulated creatinine, and nitrogen retention showed a better evolution in the group supplemented with the glutamine dipeptide when compared with the SPN group. Our results suggest a more suitable nutrition support in animals receiving L-alanyl-L-glutamine.     

Transient hypophagia in rats switched from high-fat diets with different fatty-acid pattern to a high-carbohydrate diet

The present study investigates the mechanisms underlying the transient hypophagia occurring when rats adapted to high-fat, carbohydrate-free diets are switched to high-carbohydrate, low-fat diets. The hypophagia after the high-fat, carbohydrate-free to high-carbohydrate, low-fat diet shift seems to depend on the amount of carbohydrate in the diet, since an attenuation of hypophagia was observed when high-fat, carbohydrate-free-adapted rats were switched to a medium-carbohydrate, medium-fat diet. A role of glucose intolerance in the hypophagia is supported by the attenuation of carbohydrate anorexia in rats adapted to a high-fat diet containing n -3 polyunsaturated fatty acids from fish oil (60% of fat as fish oil), which has been shown to improve glucose tolerance in rats. Furthermore, the increased plasma glucose concentration in the high-fat, carbohydrate-free diet to high-carbohydrate, low-fat shifted rats despite the suppression in food intake also suggests an involvement of glucose intolerance in the hypophagia. The failure of the inhibitor of hepatic-fatty-acid oxidation mercaptoacetate (400 micromol/kg, i.p.) to counteract carbohydrate anorexia in the HF-adapted rats argues against an involvement of fatty-acids oxidation in the inhibition of eating after high-fat, carbohydrate-free to high-carbohydrate, low-fat diet shift. This is also supported by the failure to demonstrate a relationship between plasma beta-hydroxybutyrate and the severity of the hypophagia. A role of leptin in the hypophagia seems unlikely, since plasma leptin after diet shift was unchanged. Ingestion of the high-carbohydrate, low-fat diet also produced an aversion towards this diet in high-fat, carbohydrate-free-adapted rats. It is concluded that the transient hypophagia induced by switching rats from a high-fat to a high-carbohydrate diet is not related to fatty acid oxidation but to transiently impaired carbohydrate utilization.     

Utilization and metabolic effects of a conventional and a single-solution regimen in postoperative total parenteral nutrition

A comparison was made of the effects of two intravenous regimens for postoperative total parenteral nutrition, namely, a conventional (control) regimen (group I) and a single-solution regimen of the same composition (group II). The effects examined were: hemoglobin concentration, prothrombin time, serum protein and electrolyte concentrations, and nitrogen and electrolyte balances. The 18 patients undergoing abdominal surgery were allocated at random to the two groups and the experiment was run for 3 days. During the day of the operation and the next 3 days both groups showed a decrease in the hemoglobin concentration and in the serum levels of iron, albumin, transferrin and cholesterol, while the asparagine aminotransferase increased. During total parenteral nutrition the prothrombin time and erythrocyte sedimentation rate increased in both groups. The nitrogen balance improved gradually in both groups and on the 3rd day was positive in group II. The calcium and magnesium balances indicated a higher retention and the phosphate balance a lower retention of these ions in group II than in group I. The urinary phosphate excretion rate during total parenteral nutrition decreased in both groups. This study indicates that the single-solution regimens used in intravenous nutrition caused no adverse metabolic effects and was used as efficiently as a conventional regimen in the early postoperative period.     

Influence of total parenteral nutrition on plasma fibronectin in malnourished subjects with or without inflammatory response

Plasma fibronectin, which is an alpha 2-glycoprotein of importance for the immunodefence, has been reported to decrease after starvation and in severely ill patients with cancer. To evaluate the usefulness of fibronectin as an indicator of nutritional repletion, 18 patients with gastrointestinal disorders were studied over a 2-wk period of total parenteral nutrition (TPN). According to nutritional assessment on admission the patients were divided into well nourished (n = 6) and malnourished (n = 12). For comparison nine patients with anorexia nervosa were also studied over a 3-wk period of TPN. Before and after TPN fibronectin, albumin, prealbumin, transferrin, and two acute-phase reactants, haptoglobin and orosomucoid were measured in plasma. The majority of the malnourished patients had an inflammatory reaction in contrast to only a few of the well-nourished and anorexia nervosa patients. Of the proteins measured, only fibronectin rose significantly in the malnourished patients (malnourished and anorexia nervosa), but not in the well nourished patients during TPN. Our results may indicate the usefulness of fibronectin as an indicator of short-term TPN in malnourished subjects, irrespective of the presence or absence of inflammatory response.     

Nutritional effects of branched-chain amino acids on injured rats in total parenteral nutrition

In this study, we investigated the optimal contents of branched-chain amino acids (BCAA) in a balanced amino acid infusion in laparotomized rats. The BCAA contents of four infusion solutions used were prepared to 22, 31, 40, and 49% of total amino acids, respectively. The amounts of essential amino acids except for BCAA were equal in all the solutions. Rats weighing about 240 g were infused with about 200 mg of nitrogen and 10 g of glucose daily for 7 days and evaluated for body weight change, nitrogen balance, plasma and urinary amino acid levels, and plasma constituent levels. The body weights of all the groups were approximately maintained during the infusion period. The nitrogen balance of the BCAA-31 group was more positive than that of the BCAA-22 group and was not different from those of the BCAA-40 and BCAA-49 groups. Plasma total-protein level of the BCAA-31 group was higher than that of the BCAA-22 group and was equal to those of the BCAA-40 and BCAA-49 groups. Even when the BCAA content in an amino acid infusion was increased, no abnormal elevation was observed in plasma BCAA levels. There were no differences in the other nutritional parameters among the four infusion groups. These results suggest that the BCAA contents in an amino acid infusion are enough at 31% of total amino acids for this injured rat model.     

谷氨酰胺双肽对放射性肠炎大鼠结局的影响

目的:评价丙氨酰-谷氨酰胺双肽(Ala-Gln) TPN对放射性肠炎大鼠结局的影响.方法:将70只大鼠随机分为四组,即对照组(n=10);实验组腹部接受单剂9.5 Gy60Co照射(AR),分为腹部辐射组(n=20);腹部辐射+TPN组(n=20);腹部辐射+TPN+Ala-Gln组(n=20).分别观察大鼠死亡率、体质量、小肠绒毛高度和面积,肝、脾、门静脉血、肠系膜淋巴结,腹腔渗出液作细菌培养,检测血清肿瘤坏死因子-α(TNF-α)和可溶性白细胞介素2受体(sIL-2R).结果:腹部辐射+TPN+Ala-Gln组大鼠7 d和14 d时死亡率和体质量丢失均最低;绒毛高度和面积仅轻度下降;肝、脾、门静脉血、肠系膜淋巴结和腹腔渗出液中细菌培养阳性率亦最低;血清TNF-α、sIL-2R恢复最快.结论:TPN液中添加Ala-Gln治疗放射性肠炎大鼠,可显著减少体质量丢失,减少肠道细菌移位,增加小肠绒毛高度和面积,改善机体免疫功能,降低病死率,从而显著改善放射性肠炎大鼠的预后.     

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).     

Effects of parenteral nutrition supplemented with glutamine or glutamine dipeptides on liver antioxidant and detoxication systems in rats

Our aim was to determine the effects of glutamine or alanyl glutamine parenteral supplementation on the liver oxidant/antioxidant balance and on cytochrome-P450-mediated detoxication in rats. Animals were infused for 5 d with standard total parenteral nutrition (TPN), glutamine-enriched TPN, or alanyl glutamine-enriched TPN. The hepatic concentration of glutathione was reduced, and the levels of thiobarbituric-acid-reactive substances (TBARS) were increased in animals receiving standard TPN. Both glutamine and alanyl glutamine supplementation normalized glutathione, but thiobarbituric-acid-reactive substance concentration was only decreased by ananyl glutamine. This effect was parallel to a partial recovery of the activity of antioxidant enzymes. Cytochrome-P450 liver content, cytochrome-P450-dependent monooxygenases, and antipyrine clearance were not modified by glutamine or alanyl glutamine. Our data suggest a better protection against free radicals by alanyl glutamine supplementation and an absence of effects of both glutamine and alanyl glutamine on liver oxidative metabolism.     

The differential effects of high-fat and high-fructose diets on physiology and behavior in male rats

Objectives: The purpose of the current study is to directly compare a diet high in fat with a diet high in fructose. This side-by-side comparison will allow us to determine the physiological and behavioral effects resulting from the consumption of a diet dominated by one macronutrient.

Methods: Rats were fed pelletized food containing either 60% fat or 55% fructose diet, or control chow (5.8% kcal of fat, 44.3% kcal carb) for 9 weeks. Animals performed a classic Morris Water Maze (MWM) and a reversal MWM to assess spatial and working memory near the end of the feeding period. At termination, tissue samples were collected including trunk blood, livers, fat pads, and brain punches.

Results: Animals maintained on the high-fat diet weighed more by the end of the feeding period, had a higher percent body weight change and had higher fat pad weight than the high-fructose and control group. The high-fructose group had higher serum insulin levels than the high-fat group and higher total triglycerides than control or high-fat groups. Additionally, the high-fructose group entered the target quadrant significantly less than high-fat fed animals in the reverse MWM task.

Discussion: These data suggest that fat accumulation and weight gain are influenced by the high-fat component of the Western-style diet. However, insulin resistance and elevated serum triglycerides are impacted more by high levels of fructose in the diet. Comparative data between a high-fat and high-fructose diet in a single study are novel and shed light on two of the individual components of a Western-style diet.     

Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition

Effects of different fatty acids on the development of hepatic steatosis were studied in rats receiving total parenteral nutrition (TPN). 65 rats, with internal jugular catheters, were divided into one control group (n = 8), and four experimental groups (n = 13-15 each). The control group was fed a chow diet and all experimental groups received TPN. TPN provided 300 kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fatty acid composition of the fat emulsion. Four kinds of fat emulsions rich in: 1) medium chain fatty acids (C8:0,C10:0), 2) oleic acid (C18:1 n-9), 3) linoleic acid (C18:2 n-6), 4) eicosapentaenoic acid (C20:5 n-3)/docosahexaenoic acid (C22:6 n-3), were used. These fat emulsions were prepared with: 1) a mixture of medium chain triglycerides (MCT) and soybean oil (9:1), 2) olive oil, 3) safflower oil, 4) fish oil, respectively. The results of the study demonstrated a higher hepatic lipid content in the olive oil and safflower oil groups than in the control group, whereas no significant difference was seen between the MCT and control groups. Also, no difference was observed between the fish oil and control groups. With regard to the plasma lipids, the MCT group and olive oil group produced hyperlipidaemia. The plasma of the safflower oil and fish oil groups, however, had a low lipid concentration comparable to the control group. These results suggest that TPN with a fat emulsion prepared with fish oil does not cause hyperlipidaemia nor induce hepatic steatosis in normal rats.     

Comparison of high-fat and high-carbohydrate foods in a meal or snack on short-term fat and energy intakes in obese women

The present study aimed to compare the action of high-fat and high-carbohydrate (CHO) foods on meal size (satiation) and post-meal satiety in obese women. A within-subjects design was used; each participant received all four nutritional challenges. Fifteen healthy obese women (age 21-56 years, BMI 35-48 kg/m2) participated; thirteen completed all four test days. On two test days, participants were exposed to a nutritional challenge comprising an ad libitum high-fat or high-CHO lunch. On the other two test days they were exposed to a challenge comprising an ad libitum sweet high-fat or high-CHO mid-afternoon snack. Energy and macronutrient intakes were measured at each eating episode. Visual analogue rating scales were completed periodically to record subjective feelings of appetite. When offered a high-CHO selection of foods at lunch and mid-afternoon participants consumed less energy than when offered a high-fat selection. However, post-meal satiety was similar. Total test-day energy intake was significantly higher when high-fat foods were consumed at lunch, but not as a snack. Consumption of high-fat foods at a lunch and snack increased the amount of fat consumed over the whole test day. In conclusion, energy intake of an eating episode was influenced by nutrient composition in this group of obese women. Consumption of high-fat foods at lunch or as a snack led to overconsumption relative to high-CHO foods. However, high-fat foods at meals may have greater potential to influence daily intake than at snacks, probably because meals are larger eating episodes and therefore give greater opportunity to overconsume.     

Tissue storage of vitamins A and E in rats drinking or infused with total parenteral nutrition solutions

The total parenteral nutrition (TPN) rat and its sham-operated control were used as a model to compare the metabolism and storage of vitamins A and E when they are administered intravenously or orally. Male Fisher rats were depleted of both vitamins for several months with a diet free of vitamins A or E, but containing retinoic acid for growth. TPN solutions containing aqueous dispersions of retinol, retinyl palmitate and dl-alpha-tocopheryl acetate were infused at 2.3 ml/h into the jugular veins of 10 TPN rats. Eight sham-operated control rats drank similar volumes from food cups. TPN rats received 115.3 +/- 4.5 (mean +/- SEM) micrograms of retinol equivalents and 2.2 +/- 0.2 mg of alpha-tocopherol equivalents per day; controls received 146.4 +/- 16.5 micrograms and 2.1 +/- 0.3 mg, respectively. After 7 days the animals were fasted overnight and killed. Plasma levels of retinol were 27.8 +/- 1.5 micrograms/dl for TPN rats, and 27.4 +/- 1.2 for controls. Plasma alpha-tocopherol was 1909 +/- 183 micrograms/dl for TPN rats and 1063 +/- 77 for controls. The only forms of the vitamins found in plasma after overnight fasting were unesterified retinol and unesterified alpha-tocopherol. Sham-operated control rats stored amounts of vitamins A and E similar to values reported in the literature for fed animals. TPN rats stored more of both vitamins than controls in liver, heart, and spleen, but not in testes. The enhanced liver vitamin storage by TPN rats did not appear to be due to a slight increase in lipid content. The results indicate that both vitamins A and E infused in TPN solutions maintain blood levels and are stored in tissues.     

Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition

This study was conducted to investigate the effects of fish oil and safflower oil emulsions in total parenteral nutrition (TPN) solutions on diet-induced hepatic steatosis. Rats were divided into a control group (C, n = 6) and four experimental groups (A, B, S, F, n = 11 approximately 14). The control group was fed a chow diet whereas the experimental groups received a high fat (15%, w/w) diet containing 0.1% (w/w) cholesterol. Group A received the high fat diet for 4 weeks, and was killed at the end of the fourth week to ensure that hepatic steatosis had occurred. Groups S and group F received TPN with safflower oil or fish oil emulsions, respectively, for 1 week following experimental diet feeding for 4 weeks. Group B was fed a limited amount of the high fat diet, without cholesterol, for 1 week following 4 weeks of experimental diet in order to maintain the same body weight and cholesterol intake as the TPN groups. Diet-induced hepatic steatosis was observed in the experimental groups. Fat deposition was reversed when the total caloric and cholesterol intake was reduced. Fish oil infusion ameliorated the severity of hepatic steatosis, whereas safflower oil had no effect on liver fat deposition. These results suggest that TPN with fish oil emulsions may be beneficial to patients with diet-induced hepatic steatosis.     

Glucose-based versus fat-based total parenteral nutrition (TPN): effects on hepatic function in septic patients complicated with cholestatic jaundice

A prospective study of two types of total parenteral nutrition (TPN) was carried out in 34 patients suffering from sepsis and complicated liver dysfunction. Group 1 (18 patients) received non-protein energy as glucose plus fat emulsion in a caloric ratio of 19:1, while group 2 (16 patients) received the same energy intake but with a ratio of 1:1. Group 1 exhibited higher levels of bilirubin and alkaline phosphatase with values of 93.5 +/- 25.5 mumol/l and 160 +/- 30 IU/l respectively compared to Group 2, in which the corresponding values were 81.6 +/- 32.3 mumol/l and 120 +/- 10 IU/l (p < 0.05). On the other hand, group 1 had lower levels of serum albumin and serum transferrin with values 25 +/- 1.3 g/l and 40 +/- 20% of normal, compared to group 2 in whom the corresponding values were 28 +/- 8 g/l and 48 +/- 30% of normal (p < 0.05). There were no differences between the two groups, in the absolute number of T-lymphocytes and in transaminase levels. In sepsis complicated by liver dysfunction a 50:50 glucose: fat regimen caused less disturbance of liver function than one consisting almost entirely of glucose.