Cigarette smoke during lactation in rat female progeny: Late effects on endocannabinoid and dopaminergic systems.

AIMS: Maternal smoking is considered a risk factor for childhood obesity. In a rat model of tobacco exposure during breastfeeding, we previously reported hyperphagia, overweight, increased visceral fat and hyperleptinemia in adult female offspring. Obesity and eating disorders are associated with impairment in the endocannabinoid (EC) and dopaminergic (DA) systems. Considering that women are prone to eating disorders, we hypothesize that adult female Wistar rats that were exposed to cigarette smoke (CS) during the suckling period would develop EC and DA systems deregulation, possibly explaining the eating disorder in this model. MATERIAL AND METHODS: To mimic maternal smoking, from postnatal day 3 to 21, dams and offspring were exposed to a smoking machine, 4×/day/1 h (CS group). Control animals were exposed to ambient air. Offspring were evaluated at 26 weeks of age. KEY FINDINGS: Concerning the EC system, the CS group had increased expression of diacylglycerol lipase (DAGL) in the lateral hypothalamus (LH) and decreased in the liver. In the visceral adipose tissue, the EC receptor (CB1r) was decreased. Regarding the DA system, the CS group showed higher dopamine transporter (DAT) protein expression in the prefrontal cortex (PFC) and lower DA receptor (D2r) in the arcuate nucleus (ARC). We also assessed the hypothalamic leptin signaling, which was shown to be unchanged. CS offspring showed decreased plasma 17ß-estradiol. SIGNIFICANCE: Neonatal CS exposure induces changes in some biomarkers of the EC and DA systems, which can partially explain the hyperphagia observed in female rats.

Impact of 1,25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes.

PURPOSE: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. METHODS: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. RESULTS: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). CONCLUSION: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.

Impact of 1 25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes

Abstract Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.

MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice.

BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. CONCLUSIONS: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.

Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish.

Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms.

Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. Design: This was a prospective, randomized trial. Setting: Mayo Clinic Clinical Research Unit. Patients or Participants: Thirty-two male volunteers ages 18 to 50 participated in these studies. Interventions: Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group. Main Outcome Measures: We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content. Results: Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity. Conclusions: These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.

Effects of the antipsychotic paliperidone on stress-induced changes in the endocannabinoid system in rat prefrontal cortex.

Objectives There is a need to explore novel mechanisms of action of existing/new antipsychotics. One potential candidate is the endocannabinoid system (ECS). The present study tried to elucidate the effects of the antipsychotic paliperidone on stress-induced ECS alterations. Methods Wister rats were submitted to acute/chronic restraint stress. Paliperidone (1 mg/kg) was given prior each stress session. Cannabinoid receptors and endocannabinoids (eCBs) synthesis and degradation enzymes were measured in prefrontal cortex (PFC) samples by RT-PCR and Western Blot. Results In the PFC of rats exposed to acute stress, paliperidone increased CB1 receptor (CB1R) expression. Furthermore, paliperidone increased the expression of the eCB synthesis enzymes N-acylphosphatidylethanolamine- hydrolysing phospholipase D and DAGLα, and blocked the stress-induced increased expression of the degrading enzyme fatty acid amide hydrolase. In chronic conditions, paliperidone prevented the chronic stress-induced down-regulation of CB1R, normalised DAGLα expression and reverted stress-induced down-regulation of the 2-AG degrading enzyme monoacylglycerol lipase. ECS was analysed also in periphery. Acute stress decreased DAGLα expression, an effect prevented by paliperidone. Contrarily, chronic stress increased DAGLα and this effect was potentiated by paliperidone. Conclusions The results obtained described a preventive effect of paliperidone on stress-induced alterations in ECS. Considering the diverse alterations on ECS described in psychotic disease, targeting ECS emerges as a new therapeutic possibility.

Glycyrrhizic acid prevents high calorie diet-induced metabolic aberrations despite the suppression of peroxisome proliferator-activated receptor γ expression.

OBJECTIVE: To investigate the effects of glycyrrhizic acid supplementation on glucose and lipid metabolism in rodents consuming a high-fat, high-sucrose diet. METHODS: Twenty-four male, 8-week old Sprague Dawley rats with an initial weight of 160 to 200 g were randomised into three groups (n = 6 for each group): groups A (standard rat chow), B (high-fat, high-sucrose diet), and C (high-fat, high-sucrose diet + 100 mg/kg/d of glycyrrhizic acid via oral administration). The rats were treated accordingly for 4 wk. Glycaemic parameters, lipid profile, stress hormones, and adiponectin levels were measured after the treatment. Relative gene expressions of peroxisome proliferator-activated receptor α and γ, lipoprotein lipase as well as gluconeogenic enzymatic activities in different tissues were also determined. RESULTS: Consumption of high-fat, high-sucrose diet triggered hyperglycaemia, insulin resistance, and dyslipidemia, which were effectively attenuated by supplementation with glycyrrhizic acid. Glycyrrhizic acid supplementation also effectively reduced circulating adrenaline, alleviated gluconeogenic enzymes overactivity, and promoted the upregulation of lipoprotein lipase expression in the cardiomyocytes and skeletal muscles. A high calorie diet also triggered hypoadiponectinaemia and suppression of peroxisome proliferator-activated receptor γ expression, which did not improve with glycyrrhizic acid treatment. CONCLUSION: Supplementation with glycyrrhizic acid could alleviate high calorie diet-induced glucose and lipid metabolic dysregulations by reducing circulatory stress hormones, normalizing gluconeogenic enzyme activities, and elevating muscular lipid uptake. The beneficial effects of these bioactivities outweighed the adverse effects caused by diet-induced repression of peroxisome proliferator-activated receptor γ expression, resulting in the maintenance of lipid and glucose homeostasis.

Influence of large molecular polymeric pigments isolated from fermented Zijuan tea on the activity of key enzymes involved in lipid metabolism in rat.

Influence of large molecular polymeric pigments (LMPP) isolated from fermented Zijuan tea on the activity and mRNA expression of key enzymes involved in lipid metabolism in rat was explored. The results show that intragastric infusion of high-dose LMPP (1.215 g/kg body weight) effectively suppressed the elevation in TC and LDL-C (p<0.05), and prevented the reduction in HDL-C (p<0.05), compared with the hyperlipidemia model group. LMPP significantly enhanced the activity of HL and HSL, and increased the HSL mRNA expression in the liver tissue and adipose tissue. High-LMPP treatment significantly reduced the HMG-CoA reductase expression by 56.5% in the liver compared with hyperlipidemia model group. In contrast, LDL-R expression was increased by 120% in the presence of high-LMPP treatment. These results suggest that LMPP have the hypolipidemic effect to some extent and significantly enhance HSL mRNA expression in the liver and adipose tissue, thereby increasing HSL activity in rat.

Inhibitory effect of andrographolide in 3T3-L1 adipocytes differentiation through the PPARγ pathway.

Andrographolide (AG), an active compound found in Andrographis paniculate Nees, has been shown to exert anti-inflammatory, anticancer and anti-hyperglycemic effects. However, its biological activities against obesity have not been reported. The purpose of this study was to investigate the effect of AG on the differentiation of 3T3-L1 preadipocytes. We found AG significantly inhibited not only on adipocyte differentiation induced by standard adipogenic agents and MDI, but also on the adipogenesis-related transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), as well as the expressions of the PPARγ targeted genes, such as CD36, LPL, FAS and other adiocyte markers. Taken together, our data showed AG inhibited the early stage of adipogenic differentiation, in part via the inhibition of PPARγ-dependent mechanisms.

Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats.

Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 µg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.

Beneficial effects of mangiferin on hyperlipidemia in high-fat-fed hamsters.

SCOPE: Mangiferin, a natural polyphenol, has been shown to have hypolipidemic effect in rat and mouse. However, the mechanism of action is not well understood. This study was conducted to determine the effect and mechanism of action of mangiferin on hyperlipidemia induced in hamsters by a high-fat diet. METHODS AND RESULTS: Forty male hamsters were randomly assigned to normal control, high-fat control, and high fat with mangiferin (50 and 150 mg/kg BW) groups. Mangiferin treatment significantly decreased final body weight, liver weight and visceral fat-pad weight, serum triglyceride (TG) and total free fatty acid (FFA) concentrations, hepatic TG levels and hepatic and muscle total FFA contents. Mangiferin upregulated mRNA expression of peroxisome proliferator-activated receptor-α (PPAR-α), fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT-1), but downregulated mRNA expression of sterol regulatory element-binding protein 1c (SREBP-1c), acetyl CoA carboxylase (ACC), acyl-CoA:diacylglycerol acyltransferase 2 (DGAT-2) and microsomal triglyceride transfer protein (MTP) in liver. Mangiferin also stimulated mRNA expression of PPAR-α, CD36, CPT-1 and lipoprotein lipase (LPL) in muscle. CONCLUSIONS: The results suggest that mangiferin may ameliorate hypertriglyceridemia partly by modulating the expression levels of genes involved in lipid oxidation and lipogenesis.

The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout.

Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) α, ß, and γ isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (-29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n-3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.

[Experimental studies on blood lipid regulating effects of shuanghua granules].

Hyperlipidemia plays a vital role in cardiovascular disease, and threatens our lives. The aim of this paper is to study the effects of Shuanghua granules on blood lipid in normal mice and different hyperlipidemia models. Acute and endogenous hyperlipidemia was induced in mice with yolk and Triton WR-1339 respectively. The model of hyperlipidemia in rats was set up by feeding high cholesterol diet. Then preventive effects of Shuanghua granules was observed compared with lovastatin and Zhibituo. We found that Shuanghua granules 5.6, 11.3, 22.5 g x kg (-1) could significantly reduce the serum TG level in normal mice (P < 0.01, P < 0.05). No significant difference was found in liver index, serum TG and HDL-C levels. When the mice were treated with either yolk or Triton WR-1339 in the presence of Shuanghua granules, the plasma lipoprotein levels (TC and LDL-C) were significantly reduced (P < 0.01, P < 0.05). Shuanghua granules could reduce the serum TC, TG, LDL-C, MDA, NEFA and liver TC, TG, LDL-C levels, simultaneously raise serum and liver HDL-C, serum SOD, LPL, HL, LA levels of hyperlipidemia rats (P < 0.01, P < 0.05). Shuanghua granules also significantly reduced whole blood viscosity, RV, etaP, IER and IEA (P < 0.01, P < 0.05), and lowered fatty degeneration of liver tissue. Compared with hyperlipidemia model, there was no significant increase in faeces lipoids concentrations. The results confirmed the mechanism of blood lipid regulating effects of Shuanghua granules is probably related with its antioxidation, regulating hemorheology and improving LPA, HL, LA enzymatic activity.

Site-specific modulation of white adipose tissue lipid metabolism by oleoyl-estrone and/or rosiglitazone in overweight rats.

In spite of their shared decrease of insulin resistance, oleoyl-estrone [OE], and rosiglitazone show diverging effects on body fat mass and distribution. In this study, we studied whether their effects on white adipose tissue [WAT] were due to a shared or synergistic mechanism of action. Combined effects of OE and rosiglitazone 10-day treatment on WAT lipid, cell mass/number, and the expression of key lipid metabolism and regulatory agents were studied using an adult male overweight rat model. OE decreased WAT cell mass and lipids, parameters not changed by rosiglitazone. The effects of OE and--specially--rosiglitazone were more marked in small-cell WAT (i.e., mesenteric and subcutaneous sites) than in larger cell WAT (retroperitoneal and perigonadal). OE decreased the expressions in WAT of lipogenic enzymes, lipoprotein lipase, PPARs, and SREBP1c, effects symmetrically reversed by rosiglitazone. OE showed no effects on hormone-sensitive lipase expression, which was increased by rosiglitazone. OE strongly inhibited WAT lipogenesis, leaving lipolysis unchanged, thus unbalancing (and helping mobilize) WAT lipid stores. Rosiglitazone acted practically only on small-cell WAT sites, where it favored lipogenesis, but also stimulated lipolysis, which resulted in limited changes in lipid stores. Combination of OE and rosiglitazone induced less fat loss than OE alone.

Dietary conjugated linoleic acid induces tissue-specific lipoprotein lipase mRNA modulation in high-sucrose-fed mice.

BACKGROUND/AIMS: To delineate the hypotriglyceridemic effect of conjugated linoleic acid (CLA) in mice, the effect of this fatty acid on lipoprotein lipase (LPL) and apolipoprotein C-III (ApoCIII) mRNA accumulation in muscle, adipose and liver tissue was studied. METHODS: CD-1 mice were housed in groups of 6 and randomized to one of three experimental diets for 3 weeks: SUC: 65% sucrose by weight; CLA: 1% CLA oil (34.4% c9,t11; 35.1% t10,c12 and 4.1% other conjugated isomers) and 65% sucrose, and DEX: 65% dextrose, as a control. RESULTS: LPL mRNA levels in muscle tissue were increased in the DEX group and in the CLA group (240% increase) compared with the SUC group. In contrast, LPL mRNA levels were 81% lower in epididymal adipose tissue from the CLA group compared with the SUC group. There was no effect of dietary treatments on ApoCIII mRNA accumulation in the liver. CONCLUSIONS: These data suggest that dietary CLA may induce partitioning of circulating triglycerides to muscle tissue, preventing their accumulation in adipocytes.

Hypertriglyceridemic pancreatitis: presentation and management.

Hypertriglyceridemia (HTG) is reported to cause 1-4% of acute pancreatitis (AP) episodes. HTG is also implicated in more than half of gestational pancreatitis cases. Disorders of lipoprotein metabolism are conventionally divided into primary (genetic) and secondary causes, including diabetes, hypothyroidism, and obesity. Serum triglyceride (TG) levels above 1,000 mg/dl are usually considered necessary to ascribe causation for AP. The mechanism for hypertriglyceridemic pancreatitis (HTGP) is postulated to involve hydrolysis of TG by pancreatic lipase and release of free fatty acids that induce free radical damage. Multiple small studies on HTGP management have evaluated the use of insulin, heparin, or both. Many series have also reported use of apheresis to reduce TG levels. Subsequent control of HTG with dietary restrictions, antihyperlipidemic agents, and even regular apheresis has been shown anecdotally in case series to prevent future episodes of AP. However, large multicenter studies are needed to optimize future management guidelines for patients with HTGP.

The endocannabinoid 2-arachidonoylglycerol is responsible for the slow self-inhibition in neocortical interneurons.

In the CNS, endocannabinoids are identified mainly as two endogenous lipids: anandamide, the ethanolamide of arachidonic acid, and 2-arachidonoylglycerol (2-AG). Endocannabinoids are known to inhibit transmitter release from presynaptic terminals; however we have recently demonstrated that they are also involved in slow self-inhibition (SSI) of layer V low-threshold spiking (LTS) interneurons in rat somatosensory cortex. SSI is induced by repetitive firing in LTS cells, which can express either cholecystokinin or somatostatin. SSI is triggered by an endocannabinoid-dependent activation of a prolonged somatodendritic K(+) conductance and associated hyperpolarization in the same cell. The synthesis of both endocannabinoids is dependent on elevated [Ca(2+)](i) such as occurs during sustained neuronal activity. To establish whether 2-AG mediates autocrine LTS-SSI, we blocked its biosynthesis from phospholipase C (PLC) and diacylglycerol lipases (DAGLs). Current-clamp recordings from LTS interneurons in acute neocortical slices showed that inclusion of DAGL inhibitors in the whole-cell pipette prevented the long-lasting hyperpolarization triggered by LTS cell repetitive firing. Similarly, extracellular applications of a PLC inhibitor prevented SSI in LTS interneurons. Moreover, metabotropic glutamate receptor-dependent activation of PLC produced a long-lasting hyperpolarization which was prevented by the CB1 antagonist AM251, as well as by PLC and DAGL inhibitors. The loss of SSI in the presence of intracellular DAGL blockers confirms that endocannabinoid production occurs in the same interneuron undergoing the persistent hyperpolarization. Since DAGLs produce no endocannabinoid other than 2-AG, these results identify this compound as the autocrine mediator responsible for the postsynaptic slow self-inhibition of neocortical LTS interneurons.

Xanthoma of bone associated with lipoprotein lipase deficiency.

Lipoprotein lipase (LPL) deficiency is an extremely rare congenital metabolic disorder with an accumulation of chylomicrons in the blood. We encountered a patient with an LPL deficiency leading to multiple bone xanthomas associated with hyperlipidemia. Radiographs and MRI of the humerus and femur revealed symmetrical bone lesions, and there is a possibility that these symmetrical lesions may therefore be a characteristic feature for this disorder.

Inhibition of Coix seed extract on fatty acid synthase, a novel target for anticancer activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed has been traditionally used to treat cancers in folk medicine. AIM OF THE STUDY: Study the anticancer action mechanism of Coix seed extract. MATERIALS AND METHODS: After the treatment with Coix seed extract (10 microl/ml), the residual activity of fatty acid synthase (FAS) as overall reaction, beta-ketoacyl reduction, enoyl reduction, and acetyl acetyl coenzyme A (AcAcCoA) reduction was separately detected at 340 nm in the UV-190 spectrophotometer. After rats were administrated Coix seed extract (2.5, 5.0, and 10.0 ml/kg) intragastrically for 10 days consecutively, activities of FAS, malate dehydrogenase (MDH), lipid protein lipase (LPL), hepatic lipase (HL), triglyceride (TG), and glucose-6-phosphate dehydrogenase (G-6-PD) in the plasma, liver and fatty tissues were determined. RESULTS: Experiments in vitro showed that the inhibition of Coix seed extract on FAS activity was significant and dose dependent, and two active sites inhibited were beta-ketoacyl reductases (KR) and enoyl reductase (ER). Experiments in vivo showed that Coix seed extract inhibited FAS activity in the liver, and elevated LPL and HL activity in the plasma, and effected G-6-PD activity. CONCLUSIONS: The study supports that FAS is a novel target for anticancer activity, and provides a theoretical foundation for the wide application of Coix seed extract in traditional medicine.