高脂饮食诱导高脂血症大鼠及不同器官病理变化

通过高脂饮食建立高脂血症大鼠模型,观察高脂血症大鼠体内程序性死亡受体1(PD-1)的表达变化。将40只雄性SD大鼠分为2组,分别饲喂普通饲料和高脂饲料12周,计算大鼠的肝脏、脾脏和胰腺指数,测定大鼠全血血糖,检测大鼠血清中甘油三酯(TG)、总胆固醇(T-CHO)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量,通过HE染色检测大鼠肝脏的病理变化,同时采用RT-q PCR检测PD-1 mRNA在大鼠肝脏、脾脏和胰腺组织内的表达变化。结果表明:高脂饲料组大鼠的肝脏、脾脏和胰腺指数显著高于普通饲料组;高脂饲料组大鼠的血糖显著升高;高脂饲料组大鼠血清中的TG、T-CHO、LDL-C的含量均显著高于普通饲料组,LDLC/HDL-C的比值也显著高于普通饲料组,高脂血症大鼠造模成功。HE染色显示高脂饲料组大鼠肝脏组织内均出现明显脂肪空泡。与普通饲料组相比,高脂饲料组大鼠肝脏、脾脏和胰腺组织内PD-1 mRNA的表达均显著降低,提示PD-1可能参与了高脂血症的发生和发展。     

Lipid and Phospholipid Profiling of Biological Samples Using MALDI Fourier Transform Mass Spectrometry

Here we describe a study of the feasibility of lipid and phospholipid (PL) profiling using matrix assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry (FTMS) for two different applications. In this work PL profiles of different mammalian tissues as well as those of whole cell organisms were examined. In particular, comparative analysis of lipid and PL profiles of tissues from mice fed different diets was done and, in another application, MALDI FTMS was used to analyze PL profiles of genetically modified Saccharomyces cerevisiae. Computational sorting of the observed ions was done in order to group the lipid and PL ions from complex MALDI spectra. The PL profiles of liver tissues from mice fed different diets showed a cross correlation coefficient of 0.2580, indicating significant dissimilarity, and revealed more than 30 significantly different peaks at the 99.9% confidence level. Histogram plots derived from the spectra of wild type and genetically modified yeast resulted in a cross correlation coefficient 0.8941 showing greater similarity, but still revealing a number of significantly different peaks. Based on these results, it appears possible to use MALDI FTMS to identify PLs as potential biomarkers for metabolic processes in whole cells and tissues.     

Effect of oxidative damage due to excessive protein ingestion on pancreas function in mice

The present study was undertaken to evaluate the effect of oxidative damage due to excessive protein diet on pancreas function in mice. For this purpose, thirty male (C57BL/6J) mice were randomly divided into three groups and fed on different diets as follows: group 1 was fed on a normal diet, group 2 was fed on an excessive protein diet and group 3 was fed on an excessive protein diet supplemented with 0.06 g/kg cysteamine. Each group was fed for 2 weeks, and then pancreas samples were collected to examine oxidative and antioxidant parameters and pancreas function. The results showed that ingestion of an excessive protein diet markedly increased contents of malondialdehyde (MDA) and decreased T-AOC and activities of antioxidants SOD and GSH-Px, compared with a normal diet (P < 0.05). Pancreas weight and concentration of protein, DNA and RNA were significantly higher (P < 0.05), digestive enzyme activities were significantly lower and levels of somatostatin and insulin were higher in mice fed with an excessive protein diet than those fed with a normal protein diet. In the group fed with excessive protein diet supplemented with cysteamine, oxidative stress was mitigated and pancreas function was improved. These data demonstrate that excessive protein ingestion could increase oxidative damage of free radicals on pancreas function through destroying the balance of oxidants and antioxidants.     

The Effect of a Sustained High-Fat Diet on the Metabolism of White and Brown Adipose Tissue and Its Impact on Insulin Resistance: A Selected Time Point Cross-Sectional Study

(1) Background: studies on the long-term dynamic changes in fat depot metabolism in response to a high-fat diet (HFD) on hepatic lipid deposition and insulin resistance are sparse. This study investigated the dynamic changes produced by HFD and the production of dysfunctional fat depots on insulin resistance and liver lipid metabolism. (2) Methods: mice fed a chow or HFD (45% kcal fat) diet had three fat depots, liver, and blood collected at 6, 10, 20, and 30 weeks. Anthropometric changes and gene markers for adipogenesis, thermogenesis, ECM remodeling, inflammation, and tissue insulin resistance were measured. (3) Results: early responses to the HFD were increased body weight, minor deposition of lipid in liver, increased adipocyte size, and adipogenesis. Later changes were dysfunctional adipose depots, increased liver fat, insulin resistance (shown by changes in ITT) accompanied by increased inflammatory markers, increased fibrosis (fibrosis > 2-fold, p < 0.05 from week 6), and the presence of crown cells in white fat depots. Later, changes did not increase thermogenic markers in response to the increased calories and decreased UCP1 and PRDM16 proteins in WAT. (4) Conclusions: HFD feeding initially increased adipocyte diameter and number, but later changes caused adipose depots to become dysfunctional, restricting adipose tissue expansion, changing the brown/beige ratios in adipose depots, and causing ectopic lipid deposition and insulin resistance.     

Discriminative Response to Animal, But Not Plant, Chemicals by an Insectivorous, Actively Foraging Lizard, Scincella lateralis, and Differential Response to Surface and Internal Prey Cues

Responses by the insectivorous, actively foraging scincid lizard, Scincella lateralis, to chemical cues from a plant food favored by herbivorous lizards, its ability to discriminate prey chemicals from control substances, and its relative response to internal and surface prey chemicals were studied experimentally. We presented chemical cues to the lizards on cotton swabs and recorded their tongue-flicks and biting attacks on the swabs. The lizards exhibited significantly greater tongue-flick rates and biting frequencies to prey surface cues than to plant surface chemicals from romaine lettuce, diluted cologne (pungency control), and deionized water. Responses to the plant stimuli did not differ from those to the two control stimuli, in contrast with strong responses to the same plant cues by herbivores. This finding provides the first information suggesting that chemosensory response may be adapted to diet, with responsiveness to plant stimuli evolving de novo in herbivores. Biting and tongue-flicking responses were significantly greater to cricket chemicals than to all other stimuli, among which there were no differences. Thus, the lizards are capable of prey chemical discrimination, which may be ubiquitous among actively foraging lizards. The lizards exhibited more frequent biting and higher tongue-flick rates to internal than surface prey chemicals. Although different methods of stimulus preparation are appropriate for different purposes, we conclude that prey surface chemicals available to foraging lizards are most desirable for studies bearing on location and identification of prey.     

罗格列酮对高脂血症大鼠的胰岛素抵抗作用及其机制研究

目的: 研究罗格列酮及格列齐特对高脂血症大鼠胰岛素抵抗的改善作用及其机制。方法: 建立高脂血症大鼠胰岛素抵抗模型, 并将其分为模型组、罗格列酮组和格列齐特组, 观察罗格列酮和格列齐特对其糖耐量减退、血清血糖血脂、TNF-α、Fins 含量、肝细胞TG 含量、脂质过氧化和肝肾功能等的影响。结果: 罗格列酮和格列齐特均有可能改善高脂血症致胰岛素抵抗模型病鼠的IGT 状态, 给药2 h后不同程度地降低病鼠FSG 及TNF-α浓度(P <0.05), 显著降低病鼠肝组织中TG 含量(P <0.01),明显抑制MDA 产生(P <0.01) 及增强GSH 贮量作用(P <0.01) 。罗格列酮还可降低病鼠高胰岛素水平及Fins 浓度(P <0.01), 明显降低病鼠BUN 和Cr含量(P <0.05), 提高ISI(P <0.01) 及增强SOD 活性(P <0.05) 。结论: 罗格列酮能改善高脂饲养引发的胰岛素抵抗。     

A Cumulative Effect of Food and Viruses to Trigger Celiac Disease (CD): A Commentary on the Recent Literature

Celiac disease (CD) is a type of inflammatory chronic disease caused by nutrients such as gliadin that induce a TC (T cell)-mediated response in a partially known genetical background in an environment predisposed to inflammation, including viruses and food. Various experimental and clinical observations suggest that multiple agents such as viruses and bacteria have some common, inflammatory pathways predisposing individuals to chronic inflammatory diseases including celiac disease (CD). More recently, a Western diet and lifestyle have been linked to tissue inflammation and increase in chronic inflammatory diseases. In CD, the gliadin protein itself has been shown to be able to induce inflammation. A cooperation between viruses and gliadin is present in vitro and in vivo with common mechanisms to induce inflammation. Nutrients could have also a protective effect on CD, and in fact the anti-inflammatory Mediterranean diet has a protective effect on the development of CD in children. The possible impact of these observations on clinical practice is discussed.     

The Interaction of Diet and Mitochondrial Dysfunction in Aging and Cognition

Aging is inevitable and it is one of the major contributors to cognitive decline. However, the mechanisms underlying age-related cognitive decline are still the object of extensive research. At the biological level, it is unknown how the aging brain is subjected to progressive oxidative stress and neuroinflammation which determine, among others, mitochondrial dysfunction. The link between mitochondrial dysfunction and cognitive impairment is becoming ever more clear by the presence of significant neurological disturbances in human mitochondrial diseases. Possibly, the most important lifestyle factor determining mitochondrial functioning is nutrition. Therefore, with the present work, we review the latest findings disclosing a link between nutrition, mitochondrial functioning and cognition, and pave new ways to counteract cognitive decline in late adulthood through diet.     

Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mitophagy in Female Rat Offspring

Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.     

The Essential Role of PRAK in Preserving Cardiac Function and Insulin Resistance in High-Fat Diet-Induced Diabetes

Regulated/activated protein kinase (PRAK) plays a crucial role in modulating biological function. However, the role of PRAK in mediating cardiac dysfunction and metabolic disorders remains unclear. We examined the effects of deletion of PRAK on modulating cardiac function and insulin resistance in mice exposed to a high-fat diet (HFD). Wild-type and PRAK^−/− mice at 8 weeks old were exposed to either chow food or HFD for a consecutive 16 weeks. Glucose tolerance tests and insulin tolerance tests were employed to assess insulin resistance. Echocardiography was employed to assess myocardial function. Western blot was used to determine the molecular signaling involved in phosphorylation of IRS-1, AMPKα, ERK-44/42, and irisin. Real time-PCR was used to assess the hypertrophic genes of the myocardium. Histological analysis was employed to assess the hypertrophic response, interstitial myocardial fibrosis, and apoptosis in the heart. Western blot was employed to determine cellular signaling pathway. HFD-induced metabolic stress is indicated by glucose intolerance and insulin intolerance. PRAK knockout aggravated insulin resistance, as indicated by glucose intolerance and insulin intolerance testing as compared with wild-type littermates. As compared with wild-type mice, hyperglycemia and hypercholesterolemia were manifested in PRAK-knockout mice following high-fat diet intervention. High-fat diet intervention displayed a decline in fractional shortening and ejection fraction. However, deletion of PRAK exacerbated the decline in cardiac function as compared with wild-type mice following HFD treatment. In addition, PRAK knockout mice enhanced the expression of myocardial hypertrophic genes including ANP, BNP, and βMHC in HFD treatment, which was also associated with an increase in cardiomyocyte size and interstitial fibrosis. Western blot indicated that deletion of PRAK induces decreases in phosphorylation of IRS-1, AMPKα, and ERK44/42 as compared with wild-type controls. Our finding indicates that deletion of PRAK promoted myocardial dysfunction, cardiac remodeling, and metabolic disorders in response to HFD.