Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity

Aims of the study

Fatty liver is the most common cause of abnormal liver function tests. We investigated the effect and its underlying mechanism of pomegranate flower (PGF), a traditional antidiabetic medicine, on fatty liver.

Materials and methods

At the endpoint of treatment of male Zucker diabetic fatty (ZDF) rats with PGF extract (500 mg/kg, p.o. × 6 weeks), liver weight index, hepatic lipid contents (enzymatic colorimetric methods) and droplet accumulation (Oil Red O staining) were determined. Gene profiles (RT-PCR) were analyzed in the liver of ZDF rats and in human liver-derived HepG2 cell line.

Results

PGF-treated ZDF rats showed reduced ratio of liver weight to tibia length, hepatic triglyceride contents and lipid droplets. These effects were accompanied by enhanced hepatic gene expression of peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase (ACO), and reduced stearoyl-CoA desaturase-1. In contrast, PGF showed minimal effects on expression of genes responsible for synthesis, hydrolysis or uptake of fatty acid and triglycerides. PGF treatment also increased PPAR-alpha and ACO mRNA levels in HepG2 cells.

Conclusion

Our findings suggest that this Unani medicine ameliorates diabetes and obesity-associated fatty liver, at least in part, by activating hepatic expression of genes responsible for fatty acid oxidation.     

心先安、左卡尼丁联合治疗充血性心衰临床观察

目的：评价心先安、左卡尼丁联合治疗充血性的心力衰竭临床疗效及其安全性。方法：选择2005年1月—2008年12月充血性心力衰竭（CHF）患者150例,随机分为对照组（75例）、治疗组（75例）。对照组给予常规强心、利尿、扩血管等基础抗心衰治疗。治疗组在此基础上加心先安120mg、左卡尼丁3．0加入NS100ml静滴,每日一次。治疗前、治疗一周后心脏彩超检测心功能、6分钟步行试验检测最大运动距离。结果：1周后治疗组总有效率高于对照组（P〈0．05）,两组患者心功能指标、6分钟步行试验比较差异有统计学意义。结论：联合使用心先安、左卡尼丁治疗充血性心衰是安全、有效的。     

L-carnitine could not improve hepatic warm ischemia-reperfusion injury despite ameliorated blood flow

BACKGROUND: Carnitine is applied to ameliorate ischemia-reperfusion (I/R) injury of several organs. However, application to hepatic I/R injury is not frequently reported. The aim of this study was to elucidate the effect of exogenous carnitine administration to ameliorate the warm hepatic I/R injury. MATERIALS AND METHODS: Male Wistar rats were divided into two groups, a carnitine group (Car);100 mg/kg of l-carnitine administration and a control group (C); vehicle administration. Thirty minutes after administration, the left hepatic lobes were given 60-min ischemia and then reperfused. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), tumor necrosis factor (TNF)-alpha, and lipoperoxides (LPO) were measured. Hepatic adenosine triphosphate (ATP) concentration was also measured. The hepatic blood flow was estimated using a Laser Doppler. The presence of apoptosis in the livers was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: In group Car, the blood flow of the left hepatic lobes was better recovered during the reperfusion period than in group C (P < 0.0001). Plasma levels of ALT, AST, GLDH, and TNF-alpha at 1 h after reperfusion were not significantly different between the groups. Although there were no statistical significances, ALT, AST, and TNF-alpha levels in group Car at 24 h after reperfusion tended to be higher than in group C. Plasma LPO levels were not different between the two groups. Also hepatic ATP concentration was not different between the two groups. TUNEL positive liver cells were visible only in group Car at 24 h after reperfusion, but not in the controls. CONCLUSIONS: Although carnitine administration improved the hepatic blood flow during the reperfusion period, we could not demonstrate a protective effect to the hepatic warm I/R injury.     

Impaired fasting tolerance among Alaska native children with a common carnitine palmitoyltransferase 1A sequence variant

A high prevalence of the sequence variant c.1436C→T in the CPT1A gene has been identified among Alaska Native newborns but the clinical implications of this variant are unknown. We conducted medically supervised fasts in 5 children homozygous for the c.1436C→T variant. Plasma free fatty acids increased normally in these children but their long-chain acylcarnitine and ketone production was significantly blunted. The fast was terminated early in two subjects due to symptoms of hypoglycemia. Homozygosity for the c.1436C→T sequence variant of CPT1A impairs fasting ketogenesis, and can cause hypoketotic hypoglycemia in young children.Trial registrationwww.clinical trials.gov NCT00653666 “Metabolic Consequences of CPT1A Deficiency”     

Dietary intervention with vitamin D,calcium, and whey protein reduced fat mass and increased lean mass in rats

The aim of the current study was to determine the effects and the mechanisms of inclusion of dietary whey protein, high calcium, and high vitamin D intake with either a high-sucrose or high-fat base diets on body composition of rodents. Male Wistar rats were assigned to either no whey protein, suboptimal calcium (0.25%), and vitamin D (400 IU/kg) diet (LD), or a diet containing whey protein, high calcium (1.5%), and vitamin D (10 000 IU/kg) diet (HD), and either high-fat (40% of energy) or high-sucrose (60%) base diets for 13 weeks. Liver tissue homogenates were used to determine [¹⁴C]glucose and [¹⁴C]palmitate oxidation. mRNA expression of enzymes related to energy metabolism in liver, adipose, and muscle, as well as regulators of muscle mass and insulin receptor was assessed. The results demonstrated that there was reduced accumulation of body fat mass (P = .01) and greater lean mass (P = .03) for the HD- compared to LD-fed group regardless of the background diet. There were no consistent differences between the LD and HD groups across background diets in substrate oxidation and mRNA expression for enzymes measured that regulate energy metabolism, myostatin, or muscle vascular endothelial growth factor. However, there was an increase in insulin receptor mRNA expression in muscle in the HD compared to the LD groups. In conclusion, elevated whey protein, calcium, and vitamin D intake resulted in reduced accumulation of body fat mass and increased lean mass, with a commensurate increase in insulin receptor expression, regardless of the level of calories from fat or sucrose.     

左旋卡尼汀对急性心肌梗死心功能的影响

目的观察左旋卡尼汀治疗对急性心肌梗死患者心功能的影响。方法68例急性心梗患者,随机分成治疗组及对照组,除常规治疗外,治疗组加左旋卡尼汀治疗2周。分别测量心梗后第1周、第4周、第12周患者的左室射血分数(LVEF)以及第4周、第12周患者6min步行试验。结果治疗后第12周两组患者LVEF和6min步行试验结果较治疗前已有明显恢复(P<0．001);而左旋卡尼汀治疗组的患者,较对照组亦提高,差异有显著性(P<0．05)。结论左旋卡尼汀有助于急性心肌梗死患者心功能的恢复。     

THE RELATIONSHIP BETWEEN CARNITINE AND KETONE BODY LEVELS IN DIABETIC CHILDREN

ABSTRACT. Free carnitine was significantly (p<0.001) reduced both in the ketotic (29.7±3.4 nmol/ml) and in the ketoacidotic (24.6±1.4 nmol/ml) groups when compared to controls (50.0±2.4 nmol/ml). At the same time, acylcarnitine values in the ketotic (21.2±2.4 nmol/ml) and ketoacidotic (25.4±2.3 nmol/ml) groups were significantly above the control value (4.71±0.6 nmol/ml). There was no significant difference between the two ketotic groups in carnitine derivatives. The abnormal distribution of plasma free and acylcarnitines could be reversed by insulin treatment. There was an inverse correlation between ketone body levels and free carnitine in the ketotic (r =-0.71, p<0.02) and ketoacidotic group (r =-0.71, p<0.05). However, there was no correlation between ketone bodies and acylcarnitine and between free carnitine and acylcarnitines. We concluded that the increased acylation was only partly responsible for the reduction of free carnitine in diabetic ketosis.     

The Importance Of Carnitine In The Perinatal Period

Low birth weight infants may be at risk for carnitine deficiency with resulting impairment of lipid and energy utilization.     

Comparison of gene expression profiles between white and brown adipose tissues of rat by microarray analysis

To characterize the energy metabolism in brown adipose tissue (BAT), the differences in gene expression profiles between BAT and white adipose tissue (WAT) were analyzed using a high-density cDNA microarray. RNAs isolated from two adipose tissues were hybridized to an Agilent rat cDNA Microarray that contained about 14,500 cDNA probe sets. The expression levels of 499 cDNA/ESTs were found to be at least 5-fold higher or lower in BAT than in WAT. Consistent with our previous findings, high expression levels of genes encoding uncoupling protein 1, muscle-type carnitine palmitoyltransferase and some other proteins involved in energy metabolism in BAT were found. Most of the genes encoding mitochondrial proteins, such as subunits of ATP synthase, cytochrome c oxidase, and NADH dehydrogenase, were highly expressed, reflecting possible differences in the cellular content of mitochondria between BAT and WAT. However, the expression levels of several genes encoding mitochondrial protein, such as liver mitochondrial aldehyde dehydrogenase and dicarboxylate carrier, were remarkably lower in BAT. These results may give important clues to understand the unique energy metabolism in BAT.     

Comparative acute effects of l-carnitine and dl-carnitine on hepatic catabolism of l-alanine and l-glutamine in rats

AIM: To compare the acute effects of l-carnitine (LCT) and dl-carnitine (DLC) on hepatic catabolism of l-alanine and l-glutamine in rats. METHODS: Livers from 24 h fasted and fed rats were perfused in situ. The substrates l-alanine (5 mmol/L) and l-glutamine (5 mmol/L) were employed. The gluconeogenic and ureogenic activity was measured as the difference between the rates of glucose and urea released during and before the infusion of l-glutamine or l-alanine. RESULTS: LCT (60 μmol/L) but not DLC (60 μmol/L and 120 μmol/L) increased the production of glucose and urea from l-glutamine. However, neither LCT (60 μmol/L and 120 μmol/L) nor DLC (60μmol/L and 240 μmol/L) showed any significant effect on hepatic glucose and urea production from l-alanine. CONCLUSION: The results showed a different acute effect of LCT and DLC on the activation of hepatic gluconeogenesis and ureagenesis promoted by l-glutamine, reinforcing the idea that DLC could not replace LCT.