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Objective Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, dyslipidemia and type-2 diabetes mellitus. Bile acids (BAs) bind to the farnesoid X receptor (FXR) and G protein-coupled receptor 5 (TGR5), which are involved in lipid and glucose metabolism and energy expenditure. The present study aimed to determine associations between the circulating BAs and the skeletal muscle volume (SMV), and lipid and glucose metabolism in patients with NAFLD. Methods Serum BAs and metabolic parameters were measured in 55 patients with NAFLD (median age, 55 years). The changes (Δ) in serum BA (ΔBA) and metabolic parameters were determined in 17 patients (male, n=10; female, n=7) who received nutritional counseling for 12 months. Results Spearman's test revealed that the levels of 12α-hydroxysterol (12α-OH) BAs, including deoxycholic acid (DCA), were inversely correlated with the SMV of the upper and lower limbs and the total SMV. A multivariate analysis revealed that the level of DCA was correlated with a reduced total SMV, whereas non-12α-OH BAs, including chenodeoxycholic acid (CDCA), were correlated with an increased SMV of the lower limbs. Changes in CDCA were positively correlated with the ΔSMV of the lower limbs, and inversely correlated with the Δwaist-hip ratio and Δtotal cholesterol. Changes in the total non-12α-OH BA level were positively correlated with the ΔSMV of the lower limbs. Conclusion Circulating BAs were associated with SMV. The 12α-OH BAs, including DCA were associated with reduced SMV levels, whereas non-12α-OH BAs including CDCA were associated with increased SMV levels. The molecular mechanisms underlying the association between the BA levels and the SMV remain to be explored.

Diabetes mellitus (DM), non-alcoholic fatty liver (NAFL), and obesity are associated with elevated branched-chain amino acid (BCAA) levels, but the mechanism and significance of this has not been elucidated. Eighty-four subjects were enrolled including 43 with DM. Serum BCAA levels were positively correlated with waist-hip ratio and ALT. Serum BCAA levels in subjects with DM were higher than non-DM and those in subjects with NAFL were also higher than non-NAFL. Treatment with pioglitazone and alogliptin (19 of 43 DM subjects) improved serum haemoglobin A1c and decreased BCAA levels. The decrease in BCAAs with improved glucose metabolism suggests that abnormal glucose metabolism is also a factor in elevated BCAA levels.

Objective Although the prognosis is known to be poor in cirrhosis patients associated with sarcopenia, the relationships among skeletal muscle, visceral fat, and the liver have not yet been thoroughly investigated. Therefore, the prognosis and its associations with body composition and the severity of liver disease were examined in patients with cirrhosis. Methods The skeletal muscle mass and visceral fat area were measured in 161 patients with cirrhosis, the effects of body composition on the prognosis were analyzed, and any factors that contribute to changes in body composition were assessed. Results During the mean observation period of 1,005 days, 73 patients died. Patients with sarcopenia or sarcopenic obesity had a poor prognosis, and this difference was pronounced in the subset of patients classified as Child-Pugh class A. A decreased skeletal muscle mass was strongly correlated with decreased serum albumin levels. Sarcopenia is a common feature of advanced cirrhosis, and transitions were observed from normal body composition to sarcopenia and from obese to sarcopenic obesity. Conclusion The body composition is a prognostic factor for cirrhosis, and a better body composition may be advantageous for obtaining a long-term survival in patients with cirrhosis.

Aim: To clarify the impact of visceral fat on chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and hepatitis C, we investigated the effects of lifestyle modifications on the amount of visceral fat, liver biochemistry and serum ferritin levels in patients with liver disease. Methods: Eighty-two patients (NAFLD, n = 37; hepatitis C, n = 45) were advised to adopt lifestyle modifications, including dietary changes and exercise, and these were maintained for 6 months. Bodyweight, percentage of body fat, visceral fat area (VFA) and serum alanine aminotransferase (ALT) and ferritin were measured before and after intervention. Results: In NAFLD, the mean VFA of 134.5 cm2 was significantly reduced to 125.3 cm2 after 6 months (P

Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous type 2 diabetes model, were used to clarify whether and how a low-protein diet prevents progressive diabetic nephropathy, in terms of functional and structural parameters.A low-protein diet (LPD) with 11% protein content, was compared to the normal 24% protein diet (NPD) without keeping isocaloric conditions. Daily food intake, body weight, and blood and urine chemistry were serially measured in rats from 10 through 60 weeks of age, and renal clearance studies and histological evaluations were performed at 40 and 60 weeks of age.Daily calorie intake was higher in the OLETF rats fed on the LPD than in those fed on the NPD throughout the experiment. Due to this hyperphagia, fasting blood glucose and hemoglobin (Hb)A1c were dramatically increased in the LPD-fed OLETF rats at 30 weeks and thereafter, whereas urinary protein excretion was decreased by more than half after 26 weeks in the LPD group. Plasma concentrations of total cholesterol and triglyceride were decreased in the LPD-fed OLETF rats at 40 and 60 weeks. Inulin clearance in the LPD group was higher only at 60 weeks of age. The glomerular sclerosis index (GSI) and tubulointerstitial index (TII) were preserved in the LPD group. The LPD induced a decrease in tubulointerstitial macrophage infiltration as compared with the NPD at both 40 and 60 weeks of age, but glomerular macrophage infiltration was not alleviated.A low-protein diet, despite the worsening hyperglycemia caused by hyperphagia, not only reduced proteinuria but also ameliorated hyperlipidemia in OLETF rats, thereby preserving renal function and structure in diabetic nephropathy, probably via a macrophage-mediated mechanism.

Ninety seven patients with chronic hepatitis C (CHC) and 72 with non-alcoholic fatty liver disease (NAFLD) were enrolled. Increased visceral fat area (VFA) was associated with high values of HbA1c. The variables associated with a high risk of new-onset diabetes had a VFA>101 cm(2) in CHC, but not in NAFLD.

3,4-Bis(methoxycarbonyl)-1,2-dithiete (6), 3,4,7,8-tetrakis(methoxycarbonyl)-1,2,5,6-tetrathiocin (8), and (Z,Z,Z,Z)-3,4,7,8,11,12,15,16-octakis(methoxycarbonyl)-1,2,5,6,9,10,13,14-octathiacyclohexadeca-3,7,11,15-tetraene (9) were synthesized by oxidation of titanocene dithiolene complex 4 with sulfuryl chloride, and the crystal structures of 6 and 8 were characterized by X-ray crystallographic analysis which revealed planar and twist geometries, respectively. Tetrathiocin 1, 11, and 12, and 16-membered cyclic compound 3 were also obtained by oxidation of the corresponding dithiolate or dithiolene complex. Dithiete 6 underwent tetramerization selectively to give 16-membered cyclic product 9 even at room temperature. Ring conversion reactions also proceeded among the 4-, 8-, and 16-membered unsaturated cyclic compounds possessing disulfide bonds under various conditions, such as in polar solvent or in the presence of silica gel. The ring-size selectivity of these ring conversion reactions was studied using...

Objectives:Very few reports thus far have clinically elucidated the advantages of a nutrition support team (NST) in the!eld of liver diseases. The present study retrospectively analyzed whether nutrition therapy for liver cirrhosis (LC), performed by a multidisciplinary team that includes registered dieticians, improves survival rates. Methods:In study 1, we compared survival rates between two groups of patients with LC to elucidate the effects of nutrition management by registered dieticians. The!rst group was comprised of 101 patients that received no dietary counseling from a dietician, and the second group was comprised of 133 patients that received nutritional counseling following nutrition assessment. In study 2, we split the patients who received nutritional counseling in study 1 into two groups and compared their survival rates with the objective of investigating the effects of a multidisciplinary team approach on survival rate. The!rst group was comprised of 51 patients that, in addition to regular nutritional counseling given by a dietician, regularly attended courses on liver disease given every 3 to 6 mo. The second group was comprised of 82 patients that did not attend the liver-disease courses. Results:During study 1, 34 patients in the!rst group and 20 patients in the second group died, representing a signi!cant difference (P

To clarify the impact of visceral fat on chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and hepatitis C, we investigated the effects of lifestyle modifications on the amount of visceral fat, liver biochemistry and serum ferritin levels in patients with liver disease. Eighty-two patients (NAFLD, n = 37; hepatitis C, n = 45) were advised to adopt lifestyle modifications, including dietary changes and exercise, and these were maintained for 6 months. Bodyweight, percentage of body fat, visceral fat area (VFA) and serum alanine aminotransferase (ALT) and ferritin were measured before and after intervention. In NAFLD, the mean VFA of 134.5 cm(2) was significantly reduced to 125.3 cm(2) after 6 months (P 0.001). ALT levels improved significantly between the values measured before and after intervention (P = 0.039). The VFA prior to intervention was 100 cm(2) in hepatitis C patients and it was reduced significantly after 6 months to 95.6 cm(2) (P 0.001). ALT levels also improved significantly in the hepatitis C patients (P 0.001). The serum ferritin levels also reduced in these patients. Improvements in serum ALT and ferritin levels correlated with the amount of visceral fat reduction in both groups (P = 0.046, P = 0.008, respectively). These findings demonstrate that restriction of calorie and iron intake results in reduction of visceral fat, liver enzymes and ferritin in patients with chronic liver disease. Visceral fat may be a central target for future interventions, not only in NAFLD but also in hepatitis C.

Aims: Ascites, which often complicates liver cirrhosis, is reported to be a factor that worsens the outcome. The aims of this study were to quantify body water compartment changes in cirrhotic patients, with and without ascites, and to elucidate the value of body water analysis for predicting the development of ascites. Methods: A total of 109 cirrhotic patients, with and without ascites, and 65 controls were studied. Intra- and extracellular water (ECW) in the whole body and in the arm, leg and trunk were measured using the recently developed 8-electrodes multiple-frequency bioelectrical impedance analyzer. Furthermore, patients without ascites were followed to an episode of ascites or death. Results: Patients with liver cirrhosis had significantly higher ECW ratios than controls. ECW ratios were increased in cirrhotic patients with moderate and severe disease. The ECW ratio of the trunk showed highly significant changes in cirrhotic patients with ascites. The ECW ratio correlated with age, serum albumin, and prothrombin time. A relative expansion of ECW and low albumin were predictive of further episodes of ascites (log-rank 6.94, P

実験1健康な成人女子を被験者とし, 日常飲用する濃度の3または5倍量の茶葉を浸出させた濃い濃度の烏龍茶を負荷したときの血漿脂質の経時変化を, 空腹時ならびに脂肪食経口負荷時において観察した。1) 血漿中の総コレステロール, HDLコレステロール, 中性脂肪およびリン脂質は, 空腹時および脂肪食負荷時ともに烏龍茶負荷の影響はみられなかった。2) 空腹時において血漿中のFFA量は時間の経過とともに上昇するが, 鳥龍茶負荷によりFFAはさらに高値を示し, 血中への放出が有意に増加した。脂肪食経口負荷時においても烏龍茶負荷によりFFAの放出が明らかに増加した。実験2健康な成人女子を被験者とし, 日常飲用する普通濃度の鳥龍茶を1日7杯, 6週間飲用させ血漿脂質ならびに血中LPL, H-TGL活性の変化を観察した。1) 烏龍茶の飲用により中性脂肪ならびにリン脂質は低値を示した。総コレステロールに変化はみられなかったが, 飲用後6週の時点において動脈硬化指数が改善された。2) 血中のH-TGL活性には有意な変化は認められなかったが, LPL活性は烏龍茶の飲用により高い活性値を示し, その傾向は烏龍茶の飲用終了後も引き続き観察された。

A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker rats Background Despite a large body of evidence that manipulation of dietary fat alters glomerular lesions, reports regarding the effects of dietary fat on tubulointerstitial lesions are limited. Obese Zucker rats (OZR) spontaneously develop glomerular and tubulointerstitial lesions in association with hyperlipidemia. We sought to elucidate the effects of dietary fat on glomerular and tubulointerstitial lesions in OZR versus lean Zucker rats (LZR) and to assess the involvement of macrophages in the development of these lesions. Methods We fed LZR and OZR either a low- (1%) or high-fat (20%) diet. After 30 weeks of the specified diet, the creatinine clearance (C Cr ) and renal histology as well as plasma lipid concentrations were examined. For morphological evaluation, glomerular sclerosis (GSI) and tubulointerstitial indices (TII) were each determined by a point-counting method. Infiltrating macrophages were stained immunohistochemically using an avidin-biotin complex technique. Results The high-fat diet increased the plasma low-density lipoprotein concentration in OZR. Both low- and high-fat OZR groups had higher GSI and TII than LZR receiving either diet. The high-fat diet aggravated TII but not GSI or C Cr in OZR; conversely, high fat intake worsened GSI and C Cr but not TII in LZR. Tubulointerstitial macrophages were most prominent in the high-fat OZR group, followed by the low-fat OZR group. Glomerular macrophages were similar in number in all groups. Conclusions The manipulation of dietary fat has diverse effects on the kidney. A high-fat diet aggravated macrophage-mediated tubulointerstitial lesions in OZR, whereas in LZR, the diet induced glomerulosclerosis.

The effects of Spirulina platensis on lipoprotein lipase activity and hepatic triglyceride lipase activity in post-heparin plasma were studied in fructose-induced hyperlipidemic rats. Male Wistar rats aged 3 weeks old (body weight, 54 g) were fed on the high-fructose diet (68%) or the high-fructose diets containing Spirulina at the level of 5, 10, and 15%, respectively, for 4 weeks. The dietary hyperlipidemia caused by the high-fructose diet was improved by Spirulina feeding, accompanied by a significant increase in the lipoprotein lipase activity in post-heparin plasma.

Objectives A diet restrictive in total calories, fat, iron, and protein intake reduces serum alanine aminotransferase levels in patients with long-term hepatitis C virus infection. However, whether long-term dietary therapy causes adverse effects such as malnutrition and anemia due to a shortage of energy intake is not clear. We evaluated the balance of energy intake and changes in physical and hematologic indices of nutrition after a long-term dietary therapy. Methods Twenty-two patients with long-term hepatitis C virus infection that did not respond to or who were able or unwilling to take interferon therapy were enrolled in this study. Our prescriptions included 7 mg/d or less of iron, 30 kcal · kg−1 · d−1 of energy, 1.1 to 1.2 g · kg−1 · d−1 of protein, and a fat energy fraction of 20%. Patients were followed for 24 mo. Results Mean body fat percentage was 24.6% at entry and was significantly reduced after the diet prescription. Mean serum ferritin decreased significantly from 376 ng/mL at entry to 141 ng/mL after 24 mo. Mean serum alanine aminotransferase levels decreased significantly from 66 to 49 IU/L. Mean levels of hemoglobin, serum albumin, and cholinesterase did not change significantly during the follow-up period. Conclusions These results suggest that restriction of energy, fat, iron, and protein intakes is safely tolerated, so its long-term use should be recommended to patients with long-term infection with hepatitis C virus.

It is generally accepted that iron overload plays an important role in the pathogenesis of liver cell injury in chronic hepatitis C. The present study was undertaken to evaluate whether low-iron diet improves liver function tests in patients with chronic hepatitis C.Seventeen patients with chronic hepatitis C (13 men and 4 women, 54 +/- 14 years old) that did not respond to, or were unsuitable for interferon therapy, were enrolled in this study. All patients had been pretreated with ursodeoxycholic acid for more than 12 months before the beginning of the study. Dietary iron intake was restricted to less than 7 mg/day, and the patients were followed up for 18 months.Mean daily iron intakes, calculated from food records, were 5.9 and 6.4 mg after 6 and 12 months, respectively. The mean serum ferritin decreased significantly from 362 ng/mL at entry to 179 ng/mL after 18 months. The serum unsaturated iron binding capacity level increased significantly from 163 micrograms/dL at entry to 203 micrograms/dL after 18 months. The serum aspartate aminotransferase decreased significantly from 62 IU/L at entry to 47 IU/L after 18 months, and serum alanine aminotransferase from 68 IU/L at entry to 53 IU/L after 18 months. Serum iron, hepatitis C virus-RNA titer and platelet count remained unchanged throughout the study.These results suggest that iron-restricted diet may be an important therapeutic modality for improving liver injury in patients with chronic hepatitis C.

Bis(methoxycarbonyl)-1,2-dithiete 1, the cyclic dimer 2, and the tetramer 3 were obtained by oxidation of titanocene dithiolene complex with sulfuryl chloride, and the crystal structures of 1 and 2 were determined by X-ray crystallographic analysis. Novel ring conversion reaction among the compounds was found under various conditions, such as in non-polar solvent, in polar solvent, and in the presence of silica-gel.

A comparison of the conformations and energies of (Z,Z)-, (E,Z)- and (E,E)-1,2,5,6-tetrathiacycloocta-3,7-dienes based on ab initio MO calculations is reported.

Sulfur-containing cycloalkenes possessing disulfide units 1, 2, and 3 were obtained by oxidation of cis-disodium ethene-1,2-dithiolate, and their crystal structures were determined by the X-ray crystallographic analyses. Compound 1 was found to give the ring expansion product 3 in acetonitrile even at room temperature and also form reactive thioaldehyde under irradiation.

The crystal structure of a tris(dithiolene)vanadium(IV) complex, [V(S2C2H2)3] (1), was determined. This complex shows the first instance of the nearly perfect D3h geometry in tris(dithiolene) vanadium(IV) complexes. In comparison with 1, the crystal structures of (NEt4)2[V(bdt)3] (bdt2− = 1,2-benzenedithiolate) (2) and (NEt4)2[V(tdt)3] (tdt2− = 3,4-toluenedithiolate) (3) having distorted Oh geometries were also determined by X-ray crystallography.

高果糖食で飼育した発育期および成熟期以降のラットの脂質代謝に及ぼす中国緑茶, 烏龍茶ならびに紅茶の影響を検討した。4週齢 (体重70g) ならびに8週齢 (体重210g) の雄の Wistar ラットを, それぞれ実験1, 実験2として使用した。ラットは各々68%の高果糖食にて8週間飼育した。飲料水としては, 日常飲用する普通濃度と5倍濃度の中国緑茶, 鳥龍茶, 紅茶を投与した。1) 高果糖食の飼育により, 食餌性の高脂血症がひき起こされたが, 中国緑茶, 烏龍茶投与群では, 4週齢, 8週齢のいずれにおいても血漿の中性脂肪の上昇を抑制した。しかし, 紅茶投与群においては, 4週齢においてのみ血漿中の中性脂肪の上昇を抑制した。2) 烏龍茶投与群の8週齢ラットにおいて血漿中のコレステロールが高い値を示したが, この時の総コレステロールに占めるHDLコレステロールの割合も有意に高い値を示した。3) 中国緑茶, 鳥龍茶, 紅茶を投与した8週齢ラットにおいて, 肝臓中の中性脂肪およびリン脂質が低い値を示した。