Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses

Maternal dietary Fe restriction reduced fasting plasma cholesterol and triglyceride (TG) concentrations in the fetuses, as well as decreased plasma TG levels in the adult offspring. To investigate how maternal Fe restriction was affecting fetal lipid metabolism, we investigated whether there were changes in liver lipid metabolism in the full-term fetuses. There was a approximately 27% (P < 0.05) increase in cholesterol but approximately 29% reduction (P = 0.01) in TG concentrations in the liver of the Fe-restricted fetuses. Hepatic mRNA levels of cholesterol 7alpha hydroxylase and liver X receptor-alpha (LXRalpha) were reduced by approximately 50% (P < 0.01) and approximately 34% (P < 0.01), respectively. As LXRalpha regulates expression of sterol response element binding protein-1c (SREBP-1c) expression, we measured SREBP-1c expression. There was an approximately 43% (P < 0.001) reduction in mRNA levels of SREBP-1c and its response genes, including acetyl-CoA carboxylase by approximately 35% (P = 0.01), fatty acid synthase by approximately 18% (P = 0.05), and diacylglycerol acyltransferase by approximately 19% (P = 0.03). Furthermore, protein levels of CD36 were reduced by approximately 27% (P = 0.02) in Fe-restricted fetuses. In conclusion, changes in liver cholesterol and TG concentrations in Fe-restricted fetuses may be coordinated through reduced expression of heme-containing cholesterol 7alpha hydroxylase and its regulator LXRalpha, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.     

Adaptation of adenosylmethionine metabolism and methionine recycling to variations in dietary methionine in the rat

Weanling rats were fed a casein-based diet supplemented to give dietary methionine (Met) concentrations of 0.41, 0.61, and 1.50%. After 2 weeks of feeding, the rats received intraperitoneally 800 nCi of 2-14C-labeled and/or methyl-3H-labeled L-Met. The animals were killed 20 min, 1 hr, or 2 hr after the isotope injection and the specific radioactivity of adenosylmethionine (AdoMet) as well as the total acid-soluble radioactivity was analyzed in the liver and skeletal muscle. Met concentrations of the liver and skeletal muscle were increased 20-fold by the diet containing 1.50% of Met. In the liver, but not in skeletal muscle, accumulation of AdoMet closely followed changes in Met concentration. Within 2 hr after intraperitoneal injection, the rate of disappearance of 3H label from the acid-soluble fraction was slow in both tissues; increasing in the liver and decreasing in skeletal muscle with increasing dietary Met concentration. At the same time, disappearance of 14C label was slow in both tissues in the rats fed the toxic Met diet, and also in the liver of the rats fed the Met-deficient diet. Decline of the specific radioactivity of the AdoMet pool with respect to 3H label was similar to that of 14C label in the skeletal muscle at all dietary Met concentrations. In the liver, the rate of disappearance of 14C label from the AdoMet pool was markedly increased and that of the 3H label slightly decreased with increasing dietary Met supply. Met deprivation resulted in rapid disappearance of 3H label from the hepatic AdoMet pool, whereas the disappearance of the 14C label was very slow. The results indicate that hepatic Met recycling is very effective with deficient or adequate dietary Met concentrations. In skeletal muscle, the capacity to catabolize extra Met is very limited and continuous flow of Met to liver takes place. Unlike in the liver, in skeletal muscle the transsulfuration route is not adaptable to changes in Met supply and plays a minor role in Met catabolism. The approach used to determine the efficacy and adaptation of methionine salvage pathways by following simultaneously the decline of the specific radioactivities of the methyl group and the methionyl carbon chain of AdoMet following intraperitoneal injection of double-labeled Met has several advantages over that used in literature reports. It offers a reliable means of observing these metabolic pathways in whole animals without disruption of metabolite fluxes.     

Effects of increased dietary cholesterol with carbohydrate restriction on hepatic lipid metabolism in Guinea pigs

Excessive lipid accumulation within hepatocytes, or hepatic steatosis, is the pathognominic feature of nonalcoholic fatty liver disease (NAFLD), a disease associated with insulin resistance and obesity. Low-carbohydrate diets (LCD) improve these conditions and were implemented in this study to potentially attenuate hepatic steatosis in hypercholesterolemic guinea pigs. Male guinea pigs (n = 10 per group) were randomly assigned to consume high cholesterol (0.25 g/100 g) in either a LCD or a high-carbohydrate diet (HCD) for 12 wk. As compared with HCD, plasma LDL cholesterol was lower and plasma triglycerides were higher in animals fed the LCD diet, with no differences in plasma free fatty acids or glucose. The most prominent finding was a 40% increase in liver weight in guinea pigs fed the LCD diet despite no differences in hepatic cholesterol or triglycerides between the LCD and the HCD groups. Regardless of diet, all livers had severe hepatic steatosis on histologic examination. Regression analysis suggested that liver weight was independent of body weight and liver mass was independent of hepatic lipid content. LCD livers had more proliferating hepatocytes than did HCD livers, suggesting that in the context of cholesterol-induced hepatic steatosis, dietary carbohydrate restriction enhances liver cell proliferation.     

Mechanisms and functions of membrane lipid remodeling in plants

Lipid remodeling, defined herein as post-synthetic structural modifications of membrane lipids, play crucial roles in regulating the physicochemical properties of cellular membranes and hence their many functions. Processes affected by lipid remodeling include lipid metabolism, membrane repair, cellular homeostasis, fatty acid trafficking, cellular signaling and stress tolerance. Glycerolipids are the major structural components of cellular membranes and their composition can be adjusted by modifying their head groups, their acyl chain lengths and the number and position of double bonds. This review summarizes recent advances in our understanding of mechanisms of membrane lipid remodeling with emphasis on the lipases and acyltransferases involved in the modification of phosphatidylcholine and monogalactosyldiacylglycerol, the major membrane lipids of extraplastidic and photosynthetic membranes, respectively. We also discuss the role of triacylglycerol metabolism in membrane acyl chain remodeling. Finally, we discuss emerging data concerning the functional roles of glycerolipid remodeling in plant stress responses. Illustrating the molecular basis of lipid remodeling may lead to novel strategies for crop improvement and other biotechnological applications such as bioenergy production.     

Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans

Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.     

Modulations by dietary restriction on antioxidant enzymes and lipid peroxidation in developing mice.

The effects of dietary restriction (DR) on the activities of liver superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX) and the level of lipid peroxidation (LP) in developing mice were investigated in this study. Male and female Kunmin mice were fed a standard rodent diet ad libitum (AL), 80% of AL food intake (20% DR), or 65% of AL food intake (35% DR) for 12 or 24 wk. Both 12 and 24 wk of DR resulted in retarded body weight gain in male and female mice. The activities of SOD, Cat, and GPX and the content of LP in DR male and female mice were not different (P > 0.05) from those in controls after 12 wk of DR. However, the SOD activity was increased at 24 wk in 20% DR (P < 0.05) and 35% DR (P < 0.01) male, but not in DR female, mice. The Cat activity was elevated at 24 wk in both DR male (P < 0.05 for 20% DR, P < 0.01 for 35% DR) and female (P < 0.01) mice with a greater increase in DR female (P < 0.05) than in DR male animals. GPX activity was also increased at 24 wk in DR male (P < 0.01) and female (P < 0.01) mice with a greater elevation in DR females (P < 0.05) than in DR males. Furthermore, LP was decreased at 24 wk in both DR male (P < 0.01) and female (P < 0.01) animals with a greater reduction in DR females (P < 0.01) compared with DR males. These findings indicated that 24 wk, but not 12 wk, of DR led to differential effects on liver SOD, Cat, and GPX activities and LP content in male and female mice during development, suggesting sex-associated modulations of DR on antioxidant systems in developing animals.     

低毒兴奋效应模拟热量限制调节酵母转运体基因表达及脂质代谢

【目的】已知H2O2介导的线粒体低毒兴奋效应(Mitohormesis)能模拟热量限制延长酵母寿命,但未知两者是否存在共同作用机理。【方法】利用依时菌落计数法测定酿酒酵母时序寿命(CLS),采用微阵列芯片分析ATP结合盒(ABC)转运体基因表达谱及脂质代谢模式的转变,通过酶学测定法比较超氧化物歧化酶(SOD)活性的动态变化。【结果】经热量限制、H2O2、青蒿琥酯处理后,酵母CLS有不同程度延长,细胞解毒相关ABC转运体基因表达均下调或不变,促进长链脂肪酸运输的过氧化物酶体膜ABC转运体基因以及加速固醇摄取的质膜ABC转运体基因表达则显著上调。相应地,脂质分解(如脂肪酸β-氧化)基因表达上调,脂质合成(如脂肪酸延伸及去饱和)基因表达则下调。不同处理组中催化线粒体H2O2生成的Mn-SOD活性提高,导致催化H2O2降解及转变的抗氧化酶基因表达上调。【结论】低毒兴奋效应及热量限制在酵母中发挥延寿作用,既有赖于抗氧化酶催化的活性氧(ROS)清除反应,也取决于ABC转运体介导的脂质转运及后续的脂质分解及再利用。     

Neurologically normal development of a patient with severe methionine adenosyltransferase I/III deficiency after continuing dietary methionine restriction

Background

There is not much information on established standard therapy for patients with severe methionine adenosyltransferase (MAT) I/III deficiency.

Case presentation

We report a boy with MAT I/III deficiency, in whom plasma methionine and total homocysteine, and urinary homocystine were elevated. Molecular genetic studies showed him to have novel compound heterozygous mutations of the MAT1A gene: c.191T>A (p.M64K) and c.589delC (p.P197LfsX26). A low methionine milk diet was started at 31 days of age, and during continuing dietary methionine restriction plasma methionine levels have been maintained at less than 750 μmol/L. He is now 5 years old, and has had entirely normal physical growth and psychomotor development.

Conclusions

Although some severely MAT I/III deficient patients have developed neurologic abnormalities, we report here the case of a boy who has remained neurologically and otherwise normal for 5 years during methionine restriction, suggesting that perhaps such management, started in early infancy, may help prevent neurological complications.     

Intragastric nitration by dietary nitrite: implications for modulation of protein and lipid signaling

Inorganic nitrite, derived from the reduction of nitrate in saliva, has recently emerged as a protagonist in nitric oxide (^?NO) biology as it can be univalently reduced to ^?NO, in the healthy human stomach. Important physiological implications have been attributed to nitrite-derived ^?NO in the gastrointestinal tract, namely modulation of host defense, blood flow, mucus formation and motility. At acidic pH, nitrite generates different nitrogen oxides depending on the local microenvironment (redox status, gastric content, pH, inflammatory conditions), including ^?NO, nitrogen dioxide (^?NO₂), dinitrogen trioxide (N₂O₃), and peroxynitrite. Thus, the gastric environment is a significant source of nitrating and nitrosating agents, especially in individuals consuming a nitrate/nitrite-rich diet on a daily basis. Both, the gastric lumen and mucosa contain putative targets for nitration, not only proteins and lipids from ingested aliments but also endogenous proteins secreted by the oxyntic glands. The physiological and functional consequences of nitration of gastric mediators will impact on local processes including food digestion and ulcerogenesis. Additionally, gastric nitration products (such as nitrated lipids) may be absorbed and affect systemic pathways. Thus, dietary ingestion of nitrate will have direct consequences for endogenous protein nitration, as indicated by our preliminary data.     

Mechanisms involved in tissue-specific apopotosis regulated by glucocorticoids

Physiological cell turnover is under the control of a sharp and dynamic balance of different homeostatic mechanisms such as the equilibrium between cell proliferation and cell death. These mechanisms play an important role in maintaining normal tissue function and architecture. It is well known that apoptosis is the prevalent mode of physiological cell loss in most tissues. Steroid hormones like glucocorticoids have been identified as key signals controlling cell turnover by modulating programmed cell death in a tissue- and cell-specific manner. In this sense, several reports have demonstrated that glucocorticoids are able to induce apoptosis in cells of the hematopoietic system such as monocytes, macrophages, and T lymphocytes. In contrast, they protect against apoptotic signals evoked by cytokines, cAMP, tumor suppressors, in glandular cells such as the mammary gland epithelia, endometrium, hepatocytes, ovarian follicular cells, and fibroblasts. Although several studies have provided significant information on hormone-dependent apoptosis in an specific tissue, a clearly defined pathway that mediates cell death in response to glucocorticoids in different cell types is still misunderstood. The scope of this review is held to those mechanisms by which glucocorticoids control apoptosis, emphasizing tissue-specific expression of genes that are involved in the apoptotic pathway.     

Regulation of hepatic betaine-homocysteine methyltransferase by dietary methionine

The hepatic activity of betaine-homocysteine methyltransferase is a complex function of the content of methionine in the diet. Enzyme levels are lower in the livers of rats fed a 0.3% methionine diet than in livers of animals maintained on either methionine-free or excessivemethionine (1.0%) rations. The finding that activities are increased at both extremes of the spectrum of dietary methionine intake suggests the possibility that the betaine-homocysteine methyltransferase reaction may function both to maintain tissue concentrations of methionine when intake of this amino acid is limited and to remove homocysteine when methionine intake is excessive.     

Alterations in carbohydrate metabolism in response to short-term dietary carbohydrate restriction

Dietary carbohydrate restriction (CR) presents a challenge to glucose homeostasis. Despite the popularity of CR diets, little is known regarding the metabolic effects of CR. The purpose of this study was to examine changes in whole body carbohydrate oxidation, glucose availability, endogenous glucose production, and peripheral glucose uptake after dietary CR, without the confounding influence of a negative energy balance. Postabsorptive rates of glucose appearance in plasma (R(a); i.e., endogenous glucose production) and disappearance from plasma (R(d); i.e., glucose uptake) were measured using isotope dilution methods after a conventional diet [60% carbohydrate (CHO), 30% fat, and 10% protein; kcals = 1.3 x resting energy expenditure (REE)] and after 2 days and 7 days of CR (5% CHO, 60% fat, and 35% protein; kcals = 1.3 x REE) in eight subjects (means +/- SE; 29 +/- 4 yr; BMI 24 +/- 1 kg/m(2)) during a 9-day hospital visit. Postabsorptive plasma glucose concentration was reduced (P = 0.01) after 2 days but returned to prediet levels the next day and remained at euglycemic levels throughout the diet (5.1 +/- 0.2, 4.3 +/- 0.3, and 4.8 +/- 0.4 mmol/l for prediet, 2 days and 7 days, respectively). Glucose R(a) and glucose R(d) were reduced to below prediet levels (9.8 +/- 0.6 micromol x kg(-1) x min(-1)) after 2 days of CR (7.9 +/- 0.3 micromol x kg(-1) x min(-1)) and remained suppressed after 7 days (8.3 +/- 0.4 micromol x kg(-1) x min(-1); both P < 0.001). A greater suppression in carbohydrate oxidation, compared with the reduction in glucose R(d), led to an increased (all P 相似文献   

The optimum dietary methionine requirement of juvenile humpback grouper (Cromileptes altivelis): effects on growth,micromorphology, protein and lipid metabolism

An 8-week feeding trial was conducted to evaluate optimum dietary methionine (Met) requirement of juvenile humpback grouper (Cromileptes altivelis) and the influence of dietary methionine (Met) supplementations on growth, gut micromorphology, protein and lipid metabolism. Seven isoproteic (48.91%) and isolipidic diets (10%) were made to contain 0.70, 0.88, 1.04, 1.27 1.46, 1.61 and 1.76% of dry matter Met levels. Results showed that lower survival, weight gain (WG%), protein efficiency ratio (PER), protein productive value (PPV) but higher daily feed intake (DFI) and feed conversion ratio (FCR) were observed in the Met deficient groups (0.70 and 0.88%). Optimum dietary Met requirement for humpback grouper was found to be 1.07% through the straight-broken line analysis of WG% against Met. Fish fed Met deficient diets (0.70, 0.88%) exhibited lower mRNA levels of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor-I (IGF-1), target of rapamycin (TOR) as well as S6 kinase 1 (S6K1) than other dietary groups. Whereas, expression of genes related to general control nonderepressible (GCN2) kinase i.e., GCN2 and C/EBPβ enhancer-binding protein β was upregulated in fish fed low Met diets (P < 0.05). The mRNA expression of hepatic fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1) were higher in fish fed 0.70 and 0.88% dietary Met group and the lipolytic genes, hepatic peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase-1 (CPT-1) showed an opposite variation tendency as FAS or SREBP1. Generally, the optimum Met requirement for humpback grouper was predicted to be 1.07% of dry matter.