精氨酸对全胃肠外营养大鼠肝脂肪变性的保护作用

目的：探讨精氨酸在全胃肠外营养引起的肝脂肪变性中的作用。方法：１８只正常Ｗｉｓｔａｒ大鼠随机分类三组：Ａ组,自由进食和水;Ｂ组,ＴＰＮ;Ｃ组,ＴＰＮ＋精氨酸。实验７天后测体重、肝功能、门脉胰岛素、胰高血糖素、肝重、肝内脂肪和肝组织学检查。结果：Ｂ组门静脉胰岛素与胰高血糖素比值较Ａ组升高,Ｃ组门静脉Ｉ／Ｇ值较Ｂ组降低。Ｂ组肝内脂肪较Ａ组增加,Ｃ组肝内脂肪较Ｂ组减少。结论：精氨酸可以减少ＴＰＮ引起的肝     

Chronic parenteral nutrition induces hepatic inflammation, steatosis, and insulin resistance in neonatal pigs

Prematurity and overfeeding in infants are associated with insulin resistance in childhood and may increase the risk of adult disease. Total parenteral nutrition (TPN) is a major source of infant nutritional support and may influence neonatal metabolic function. Our aim was to test the hypothesis that TPN induces increased adiposity and insulin resistance compared with enteral nutrition (EN) in neonatal pigs. Neonatal pigs were either fed enteral formula orally or i.v. administered a TPN mixture for 17 d; macronutrient intake was similar in both groups. During the 17-d period, we measured body composition by dual-energy X-ray absorptiometry scanning; fasting i.v. glucose tolerance tests (IVGTT) and hyperinsulinemic-euglycemic clamps (CLAMP) were performed to quantify insulin resistance. On d 17, tissue was collected after 1-h, low-dose CLAMP for tissue insulin signaling assays. TPN pigs gained less lean and more body fat and developed hepatic steatosis compared with EN pigs. After 7 and 13 d, IVGTT showed evidence of insulin resistance in the TPN compared with the EN group. Fasting plasma glucose and insulin also were higher in TPN pigs. CLAMP showed that insulin sensitivity was markedly lower in TPN pigs than in EN pigs. TPN also reduced the abundance of the insulin receptor, insulin receptor substrate 1, and phosphatidylinositol 3 kinase in skeletal muscle and liver and the proliferation of total pancreatic cells and β-cells. Hepatic proinflammatory genes as well as c-Jun-N-terminal kinase 1 phosphorylation, plasma interleukin 6, and tumor necrosis factor-α were all higher in TPN pigs than in EN pigs. The results demonstrate that chronic TPN induces a hepatic inflammatory response that is associated with significant insulin resistance, hepatic steatosis, and fat deposition compared with EN in neonatal pigs. Further studies are warranted to establish the mechanism of TPN-induced insulin resistance and hepatic metabolic dysfunction and whether there are persistent metabolic consequences of this lifesaving form of infant nutritional support.     

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 versus glucose-fat mixture in the course of total parenteral nutrition: effects on substrate utilisation and energy metabolism in malnourished children

Energy substrate utilisation was evaluated over 21 days in two groups of malnourished children on total parenteral nutrition (TPN). Non-protein energy was infused as glucose (Group A; n = 7) or as a glucose/fat (1:1 v/v) mixture (Group B; n = 10). Results indicated that: 1) net glucose oxidation was related to glucose intake; 2) glucose storage was elevated in group A; 3) net fat synthesis occurred earlier in group B together with constant net fat oxidation which was inversely related to glucose intake (r = -0.89, p < 0.001); 4) lipogenesis from glucose occurred only when glucose intake exceeded 19.3g/kg/d; 5) energy expenditure increased by 36% (group A) and 18% (group B) during renutrition; 6) 73% and 82% of the energy administered in excess of energy required was stored in group A and B respectively. Hence, glucose/fat infusion appears to be more energy-efficient than glucose-alone in TPN of malnourished children.     

Significance of administration of fat emulsion: hepatic changes in infant rats receiving total parenteral nutrition with and without fat

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present animal study focused on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. Thirty infant (3-week-old) male SD rats weighing 60-70 g were randomly allocated to five groups (n = 6): the OD group received an oral diet, the FT group received an oral diet and was fasted overnight on the last day of experiment before sacrifice, the 0% fat group received TPN without fat, the 20% fat group received TPN with 20% of calories from fat emulsion, and the 40% fat group received TPN with 40% of calories from fat emulsion. All TPN regimens were isocaloric, isonitrogenic, and administered for 4 days. In the 0% fat group, plasma levels of liver enzymes were significantly higher than in the other groups. Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the 0% fat group. The results of this study in infant rats indicate the importance of including fat in the TPN regimen in order to prevent the abnormal hepatic changes associated with the excessive administration of fat-free TPN.     

Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide.

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.     

Total parenteral nutrition energy composition affects small intestinal disaccharidase activity in the newborn miniature pig

Total parenteral nutrition (TPN) decreases disaccharidase activity in the small intestine of humans and miniature piglets. The possibility, however, that specific components of TPN (eg, the energy mix) will increase disaccharidase activity has largely been unexplored. The identification of such components would be particularly useful in the treatment of premature infants with immature gastrointestinal tracts and patients with small intestinal mucosal disease associated with decreased disaccharidase activity. To determine whether the TPN energy composition affects small intestinal disaccharidase activity, 7-day-old miniature piglet littermates were randomized to receive TPN containing either glucose (group G) or glucose and fat (group G/F) as the nonnitrogen energy source(s). The TPN regimens were isonitrogenous and isoenergetic. The piglets were not allowed oral intake during the 7 days they were maintained on TPN. At 14 days of age the piglets were killed and the small intestines analyzed for weight, protein, DNA, and disaccharidase activity. Body weight was similar between groups at both the beginning and end of the study. The TPN regimen did not affect small intestinal weight of protein and DNA content. However, jejunal and ileal sucrase and ileal maltase activities (mumol/min.kg body wt +/- SD) were greater in group G than those in group G/F (28 +/- 9 vs 19 +/- 11, p = 0.04; 13 +/- 7 vs 7 +/- 4, p = 0.037; and 31 +/- 8 vs 19 +/- 10, p = 0.0088, respectively). No differences in lactase activity were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in hepatic mitochondrial function during total parenteral nutrition in immature rats

To evaluate the effects of total parenteral nutrition (TPN) on hepatic mitochondrial function in immature rats, changes in hepatic energy charge levels and oxidative phosphorylation rates of hepatic mitochondria were studied along with the examination of serum chemical test. Male Wistar rats weighing 30 to 45 g were used and randomized into TPN (n = 8), enteral (n = 7), and control groups (n = 8). Parenteral and enteral groups were fed with TPN solution containing 19.3% dextrose, 3.19% amino acids, 1.05% fat emulsion, minerals and vitamins, and the control group with rat chow. The number of calories per kilogram per day was 550 x 1/4 on the 1st day, 550 x 1/2 on the 2nd, 550 x 3/4 on the 3rd, and 550 x 1 on the 4th day, based on the body weight on the 1st day. After the 5th day, 550 Kcal/kg/day was given, based on the body weight of the respective day. After 13-day feeding, hepatic energy charge (EC), phosphorylation rate (PR) of hepatic mitochondria and serum chemical examination were carried out. EC was 0.871 +/- 0.016 in the control group, 0.830 +/- 0.019 in the enteral, and 0.785 +/- 0.011 in TPN group (p less than 0.001, compared with control group). PR was 138.9 +/- 1.9, 133.0 +/- 6.7, 111.0 +/- 4.3, respectively, (p less than 0.05, compared with control and enteral groups). There was no difference between the three groups on SGOT, SGPT, and total bilirubin. TPN group showed a deterioration of hepatic phosphorylation rate and energy charge in spite of normal serum transaminase levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同脂肪乳剂对阻塞性黄疸大鼠肝脏功能和形态学的影响

目的：比较不同脂肪酸来源的全胃肠外营养（TPN）对胆总管结扎大鼠肝脏功能和形态学的影响。观察不同脂肪酸对阻塞性黄疸大鼠受损肝脏的作用,为临床阻塞性黄疸患应用TPN提供实验依据。方法：采用SD大鼠36只,随机分4组,每组9只,其中A组为假手术＋经口饮食对照组;余3组均行胆总管结扎术：B组为经口饮食对照组,C,D组分别给予以长链（LCT）或中长链脂肪酸（MCT／LCT）为脂肪来源的TPN。结果：应用长链脂肪酸大鼠的血清AKP,g-GT,血清总胆红素,直接胆红素和胆汁酸水平均高于应用中长链脂肪酸大鼠。对实验大鼠肝脏形态学观察发现,应用LCT的大鼠肝细胞损害较经口饮食对照大鼠有所加重,而应用MCT／LCT的大鼠肝细胞损害未见加重。结论：短期应用合理糖脂比,热氮比和合适脂肪来源的TPN并不加重阻塞性黄疸大鼠的肝脏损害和胆红素代谢紊乱。     

Trans fatty acids in maternal milk lead to cardiac insulin resistance in adult offspring

OBJECTIVE: Trans fatty acids (TFAs) are derived from vegetable oil hydrogenation and can be found in most manufactured food products. Our main objective was to evaluate the effects of TFA consumption by lactating dams on cardiac glucose metabolism of adult offspring by analyzing glucose transporter-4 in the left ventricle. To investigate the energy homeostasis, insulin sensitivity and hepatic glycogen content were also measured. METHODS: Lactating Wistar rats were divided into a control group or a TFA group. The control group received a diet containing soybean oil, and the TFA group received a diet containing partially hydrogenated vegetable oil (total trans concentration of about 10.58 mg/g, 11.75%, of total fat) throughout the lactation period. At weaning, pups from both groups received a standard chow until 60 d of age, at which time the quantity of glucose transporter-4 in the left ventricle and hepatic glycogen were measured. Moreover, insulin sensitivity was analyzed by assessing the insulin/glucose ratio and the homeostatic model assessment index. RESULTS: TFA consumption by the pups during lactation led to a significant decrease in the cardiac content of glucose transporter-4 (P < 0.05) and in the hepatic content of glycogen (P < 0.05). Moreover, we observed impaired insulin sensitivity in the TFA group (insulin/glucose ratio and homeostatic model assessment index, P < 0.05) in adulthood. CONCLUSION: Our data suggest that the consumption of hydrogenated fat, rich in TFAs, by the mothers during the lactation period caused cardiac insulin resistance in the adult progeny, thus reinforcing the hypothesis that early adaptations may cause deleterious consequences later in life.     

MCT/LCT emulsion ameliorate liver fat deposition in insulin-treated diabetic rats receiving total parenteral nutrition

This study was designed to investigate the effects of high energy infusion and insulin treatment on plasma and liver lipids in diabetic rats receiving total parenteral nutrition (TPN). Diabetes was induced in rats by streptozotocin. The diabetic rats were assigned to two TPN groups to receive either long chain triglyceride (LCT) or medium chain triglyceride (MCT)/LCT (1:1) as a fat source. The TPN solutions were isonitrogenous, isocaloric and identical in nutrient composition except for the fat emulsion. All rats received the TPN solution at an energy level of 35|kcal/100|g of body weight. The LCT and MCT/LCT groups were further divided into two subgroups, depending on whether they were treated with insulin. The results demonstrated that, between the MCT/LCT and LCT groups, no differences were observed in body weight and nitrogen retention, as well as the concentrations of plasma glucose, nonesterified fatty acids, beta-hydroxybutyrate, and total cholesterol. Diabetic TPN rats without insulin treatment had weight loss and negative nitrogen balance during the experiment. Diabetic TPN rats treated with insulin, however, demonstrated less weight loss and positive nitrogen retention. Insulin treated groups had significantly higher liver fat content than did those without insulin treatment. Furthermore, liver fat content was significantly higher in the LCT group than in the MCT/LCT group among insulin treated TPN rats. These results suggest that compared with the LCT emulsion, infusion of the MCT/LCT emulsion ameliorated liver fat deposition in insulin-treated diabetic rats receiving TPN.     

Total parenteral nutrition with and without fat as substrate for growth of rats and transplanted hepatocarcinoma

Differential effects of total parenteral nutrition (TPN) on host nutrition and growth of cancer are unclear. Growth of adult ACI-N rats bearing transplanted Morris hepatocarcinoma no. 3924A given TPN with or without fat was studied in comparison with Purina Chow-fed, fasting, and semifasting (either amino acid or dextrose alone) rats over 5 days. The isocaloric, isonitrogenous TPN regimens with or without fat maintained body weight and nitrogen balance of cancer-bearing rats equally well. When compared with Chow-fed rats, the volume of the cancer, its weight, doubling time, protein content, and incorporation of thymidine into DNA were similar in rats given TPN either with or without fat. Although the volume of the cancer decreased in fasting and semifasting rats, the nutritional status of the host was also impaired. Administration of TPN to cancer-bearing rats was associated with an abnormal increase in serum lactic acid level, which was not ameliorated by the use of fat to reduce the carbohydrate load. Although TPN with and without fat maintains the nutritional status, hepatomegaly and hepatic steatosis limit the administration of carbohydrate and fat as energy substrates in this system.     

谷胱甘肽防止幼兔全胃肠外营养所致肝损害

目的研究氧化损伤及凋亡在全胃肠外营养(TPN)相关肝损害机制中的作用,并探讨谷胱甘肽防止TPN相关肝损害的有效性。方法将35只出生后6～8天的新西兰兔分为3组:正常对照组(n=12,母乳喂养);PN组(n=12,全肠外营养组,持续静脉营养10天);PN+GSH组(n=11,全肠外营养+还原型谷胱甘肽20mg/kg·d)。10天后比较3组间肝功能、肝脏光镜和电镜病理变化、TUNEL法检测肝细胞凋亡以及肝组织丙二醛(MDA)含量。结果PN组血直接胆红素、胆汁酸均明显高于正常对照组和PN+GSH组(P<0.05)。PN+GSH组病理无胆管扩张和胆汁淤积表现,电镜超微结构变化与病理相符。PN组肝组织MDA含量及肝细胞凋亡阳性率明显高于对照组和PN+GSH组(P<0.05,P<0.01)。结论氧化损伤及凋亡在TPN相关肝损害机制中可能起着重要作用;谷胱甘肽可明显减轻TPN所致肝细胞损害,可能与其抗氧化、抗凋亡作用有关。     

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.     

Host and tumor growth and energy substrates in blood of hepatoma-bearing rats receiving high-fat parenteral infusions

We examined the effects of isocaloric carbohydrate-based TPN vs fat-based TPN on plasma levels of energy substrates and insulin and on growth of Morris Hepatoma 7777 and host animals. Hepatoma-bearing rats fed similar diets ad libitum served as controls. Although no differences in tumor growth were observed, host weight loss was less in parenterally than in orally fed animals. Liver lipid and plasma free fatty acids and triglycerides in tumor-bearing and normal rats infused high-fat TPN were markedly higher than in all other groups, suggesting that this level of lipid infusion exceeds the rate of utilization. Plasma glucose and insulin in tumor-bearing rats infused high-fat TPN were higher than in all other groups, which may indicate insulin resistance. Replacing glucose energy in TPN with lipid does not appear to reduce glucose availability to tumors but does have potentially deleterious effects on the host.     

Pattern of energy storage in the liver and muscle of rats submitted to total parenteral nutrition

TPN was administered to young male rats for 10 days at a low (270 kcal/kg/day) and a high (250 kcal/kg/day) energy level, with an isonitrogenous supply (0.9 g N/kg/day). The non-protein calories were divided into three energy substrate ratios: 0% Fat 100% Glucose , 6% Fat 94% Glucose , and 60% Fat 40% Glucose . Glycogen, acylglycerols and enzyme activities of the heart and some skeletal muscles (tib. anterior, ext. dig. longus and soleus) were unaffected by the various intravenous regimens. The glycogen content of the liver was significantly higher in both low fat groups. There was also a clear tendency in all groups to lower values of glycogen as the energy level of the TPN increased. The opposite trend was seen with acylglycerols, which were highest in the high glucose and high fat groups. The highest acylglycerol content was found in the high fat group at the high energy level. This study demonstrates that unbalanced intravenous regimens, without fat or with a fat overload (20 g/kg/day), seem to alter the storage pattern of glycogen and fat in the liver, particularly when hypercaloric regimens are given. The heart and skeletal muscles seemed to be protected from this effect.     

Effect of structured lipids as energy substrate after hepatectomy in rats with streptozocin-induced diabetes.

The suitability of energy substrates for use by the remnant liver after 70% hepatectomy was studied in relation to the hepatic energy status in diabetic rats. Rats with streptozocin-induced diabetes underwent 70% hepatectomy and were divided into five groups receiving total parenteral nutrition (TPN) for 24 h. One group received standard TPN without fat, and four groups respectively received standard TPN with long-chain triglycerides (LCTs), medium-chain triglycerides (MCTs), mixed triglycerides (MIX), or structured lipids (SLs) as a 10% lipid emulsion. The latter groups received 60% of nonprotein calories per day with fat emulsion (LCT, MCT, MIX, or SL), and the remaining 40% with glucose. The group that received 100% of nonprotein calories per day with glucose was defined as the TPN group. All rats in the TPN group died from nonketotic hyperosmolarity within 24 h. The blood ketone body ratio (acetoacetate/beta-hydroxybutyrate), the energy charge level of the remnant liver, and the cumulative excretion of 14CO2 in expired breath during 6 h after [14C]glucose administration were all significantly higher in the SL group than in the other groups 24 h after hepatectomy. These findings suggest that SL may be a superior energy substrate to other triglyceride preparations during the immediate posthepatectomy phase in diabetic patients.     

Effect of short-term consumption of a high fat diet on glucose tolerance and insulin sensitivity in the rat

The mechanism by which the consumption of high fat, low carbohydrate diets impair glucose tolerance and decrease insulin sensitivity is poorly understood. In an attempt to clarify this question, intravenous glucose tolerance and insulin action in the liver and skeletal muscle were examined in rats after two weeks feeding of either a high fat (HF: 66% energy as fat) or a low fat (LF: 12% energy as fat) diet. Both diets had a P/S ratio (ratio of polyunsaturated to saturated fat in the diet) of 1.3. The high fat diet resulted in mild impairment of intravenous glucose tolerance. Postprandial glucose levels were elevated in the presence of a sustained insulin response. In vitro insulin-stimulated glucose utilisation was decreased significantly in soleus muscle of HF rats, as indicated by decreased [14C]glucose incorporation into muscle glycogen. In contrast, muscle lipogenesis from glucose was not affected by dietary composition. There was no difference in insulin binding to soleus muscle of HF and LF rats, indicating a dissociation between insulin receptor binding and post-receptor metabolic events. Dietary composition did not influence the incorporation of increasing [14C]glucose loads into muscle glycogen or lipid in vivo. However, the HF diet was associated with reduced incorporation of [14C]glucose into lipids and glycogen in the liver and, to a smaller extent, reduced incorporation into adipose tissue lipids in vivo. These results suggest that the mechanism by which HF diets impaired glucose tolerance was mainly hepatic in origin. Decreased glucose uptake, secondary to reduced glucokinase activity, may result in a reduction in glucose utilisation in the liver.     

Beneficial effect of chungkukjang on regulating blood glucose and pancreatic beta-cell functions in C75BL/KsJ-db/db mice

The current study investigated the antidiabetic effect of chungkukjang, a widely used traditional Korean soybean fermentation food, in a type 2 diabetic animal model, C57BL/KsJ-db/db mice. After a 2-week acclimation period, the db/db mice (male, 5 weeks old) were divided into three groups: diabetic control (AIN-76 diet), chungkukjang (5 g/100 g of diet), and rosiglitazone (0.005 g/100 g of diet). The supplementation of chungkukjang induced a significant reduction of blood glucose and glycosylated hemoglobin level, and it improved insulin tolerance compared to the diabetic control group. Plasma and pancreatic insulin levels of the chungkukjang-supplemented group were significantly higher than those of the diabetic control mice, and the plasma glucagon level was also significantly different. The supplementation of chungkukjang and rosiglitazone significantly elevated hepatic glucokinase activity with a simultaneous reduction of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activity in the db/db mice compared to the diabetic control mice. In addition, the chungkukjang-supplemented group had an increased hepatic glycogen content compared to the diabetic control and rosiglitazone-supplemented groups. Consequently, these results suggest that chungkukjang may be beneficial in improving insulin resistance and hyperglycemia in type 2 diabetic animals that are partly medicated by the regulation of hepatic glucose enzymes and insulin sensitivity in peripheral tissues.     

Supplementation with Vitis vinifera L. skin extract improves insulin resistance and prevents hepatic lipid accumulation and steatosis in high-fat diet–fed mice

Nonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09’s influence on high-fat (HF) diet–induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200 mg/[kg d]) for 12 weeks. Our results showed that ACH09 reduced HF diet–induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate–activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet–fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet–induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09’s protective effect.