Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia.

High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

Gualou Xiebai Banxia decoction ameliorates Poloxamer 407-induced hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis. OBJECTIVE: The present study aimed to examine GLXBBX's preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats. MATERIALS AND METHODS: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats' plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected. RESULTS: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1). CONCLUSION: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.

Hypothalamic Renin-Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet.

The brain renin-angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.

Trilactic glyceride regulates lipid metabolism and improves gut function in piglets.

Glycerol-lactate esters are energy supplements for exercise, but effects of trilactic glyceride (TLG) on intestinal function and hepatic metabolism are unknown. We found that dietary supplementation with 0.5% TLG to weanling piglets decreased plasma concentrations of low-density lipoprotein and gamma-glutamyl transferase but increased those of D-xylose and high-density lipoprotein. TLG supplementation enhanced mRNA levels for fatty acid synthase (FASN) and SLC27A2 in white adipose tissue; insulin receptor in duodenum; aquaporin-8 in ileum, jejunum and colon; aquaporin-10 in duodenum and ileum; nuclear factor like-2 in jejunum and colon; glutathione S-transferase and phosphoenolpyruvate carboxykinase-1 in intestines; and abundances of claudin-1 and occludin proteins. TLG supplementation decreased mRNA levels for: hepatic hormone-sensitive lipase E, lipoprotein lipase, FASN, insulin-like growth factor-binding protein-3, and SLC27A2; and intestinal lipoprotein lipase, FASN and NADPH oxidase. Furthermore, TLG supplementation enhanced abundances of genus Bifidobacterium, while reducing abundances of family Enterobacteriaceae in ileum, colon and cecum; jejunal caspase-3 protein and diarrhea rate. In conclusion, dietary supplementation with TLG modulated lipid metabolism and alleviated diarrhea by improving intestinal function and regulating intestinal microflora in piglets.

Impacts of Dietary Protein from Fermented Cottonseed Meal on Lipid Metabolism and Metabolomic Profiling in the Serum of Broilers.

Dietary protein from fermented cottonseed meal (FCSM), widely used in poultry diets in China, had regulating effects on lipid metabolism. To understand the effects of FCSM on lipid metabolism in broilers, we analyzed the biochemical indexes, enzyme activity, hormone level and metabolites in serum responses to FCSM intake. One hundred and eighty 21-d-old Chinese yellow feathered broilers (536.07±4.43 g) were randomly divided into 3 groups with 6 replicates and 3 diets with 6 % supplementation of unfermented CSM (control group), FCSM by C. Tropicalis (Ct CSM) or C. tropicalis plus S. Cerevisae (Ct-Sc CSM). Result showed that: (1) FCSM intake decreased significantly the content of triglyceride (TAG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P<0.05) in serum; (2) FCSM intake could significantly increase enzyme activity of acetyl CoA carboxylase (ACC), lipoprotein lipase (LPL), fatty acid synthase (FAS) and hormone sensitive lipase (HSL) (P<0.05); (3) Ct-Sc CSM intake increased significantly the levels of adiponectin (ADP) (P<0.05); (4) FCSM intake caused significant metabolic changes involving glycolysis, TCA cycle, synthesis of fatty acid and glycogen, and metabolism of glycerolipid, vitamins B group and amino acids. Our results strongly suggested that FCSM intake could significantly affect lipid metabolism via multiple pathways. These findings provided new essential information about the effect of FCSM on broilers and demonstrated the great potential of nutrimetabolomics, through which the research complex nutrients are included in animal diet.

Krüppel-like factor 14 inhibits atherosclerosis via mir-27a-mediated down-regulation of lipoprotein lipase expression in vivo.

BACKGROUND AND AIMS: Krüppel-like factor 14 (KLF14) is known to play a role in atherosclerosis, but the underlying mechanisms are still largely unknown. The aim of our study was to explore the effects of KLF14 on lipid metabolism and inflammatory response, providing a potential target for lowering the risk of atherosclerosis-causing disease. METHODS AND RESULTS: mRNA and protein levels of KLF14 were significantly decreased in oxidized low-density lipoprotein (oxLDL)-treated macrophages and in the atherosclerotic lesion area. Chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays were used to confirm that KLF14 positively regulated miR-27a expression by binding to its promoter. We also found that KLF14 could restored appropriate cellular lipid homeostasis and inflammatory responses via negatively regulating lipoprotein lipase (LPL) expression in THP1-derived macrophages through miR-27a. In addition, gypenosides (GP), a KLF14 activator, delayed the development of atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. CONCLUSIONS: KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation.

Allium hookeri Root Extract Inhibits Adipogenesis by Promoting Lipolysis in High Fat Diet-Induced Obese Mice.

Allium hookeri (AH) is widely consumed as a herbal medicine. It possesses biological activity against metabolic diseases. The objective of this study was to investigate effects of AH root water extract (AHR) on adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice. AHR inhibited lipid accumulation during adipocyte differentiation by downregulation of gene expression, such as hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and an adipogenic gene, CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes. Oral administration of AHR significantly suppressed body weight gain, adipose tissue weight, serum leptin levels, and adipocyte cell size in HFD-induced obese mice. Moreover, AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes, such as 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding transcription factor (SREBP)-2, and low-density lipoprotein receptor, as well as fatty acid synthesis genes, such as SREBP-1c and fatty acid synthase. Serum triglyceride levels were also lowered by AHR, likely as a result of the upregulating gene involved in fatty acid ß-oxidation, carnitine palmitoyltransferase 1a, in the liver. AHR treatment activated gene expression of peroxisome proliferator-activated receptor-γ, which might have promoted HSL and LPL-medicated lipolysis, thereby reducing white adipose tissue weight. In conclusion, AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in adipogenesis, lipogenesis, and lipolysis in the white adipose tissue and liver.

Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet.

Red raspberries (Rubus idaeus) contain numerous phenolic compounds with purported health benefits. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is a primary raspberry flavor phenolic found in raspberries and is designated as a synthetic flavoring agent by the Food and Drug Administration. Synthetic raspberry ketone has been demonstrated to result in weight loss in rodents. We tested whether phenolic-enriched raspberry extracts, compared with raspberry ketone, would be more resilient to the metabolic alterations caused by an obesogenic diet. Male C57BL/6J mice (8 weeks old) received a daily oral dose of vehicle (VEH; 50% propylene glycol, 40% water, and 10% dimethyl sulfoxide), raspberry extract low (REL; 0.2 g/kg), raspberry extract high (REH; 2 g/kg), or raspberry ketone (RK; 0.2 g/kg). Coincident with daily dosing, mice were placed on a high-fat diet (45% fat). After 4 weeks, REH and RK reduced body weight gain (approximately 5%-9%) and white adipose mass (approximately 20%) compared with VEH. Hepatic gene expression of heme oxygenase-1 and lipoprotein lipase was upregulated in REH compared with VEH. Indirect calorimetry indicated that respiratory exchange ratio (CO2 production to O2 consumption) was lower, suggesting increased fat oxidation with all treatments. REH treatment increased total ambulatory behavior. Energy expenditure/lean mass was higher in REH compared with REL treatment. There were no treatment differences in cumulative intake, meal patterns, or hypothalamic feed-related gene expression. Our results suggest that raspberry ketone and a phenolic-enriched raspberry extract both have the capacity to prevent weight gain but differ in the preventative mechanisms for excess fat accumulation following high-fat diet exposure.

Diacylglycerol Lipase-Alpha Regulates Hippocampal-Dependent Learning and Memory Processes in Mice.

Diacylglycerol lipase-α (DAGL-α), the principal biosynthetic enzyme of the endogenous cannabinoid 2-arachidonylglycerol (2-AG) on neurons, plays a key role in CB1 receptor-mediated synaptic plasticity and hippocampal neurogenesis, but its contribution to global hippocampal-mediated processes remains unknown. Thus, the present study examines the role that DAGL-α plays on LTP in hippocampus, as well as in hippocampal-dependent spatial learning and memory tasks, and on the production of endocannabinoid and related lipids through the use of complementary pharmacologic and genetic approaches to disrupt this enzyme in male mice. Here we show that DAGL-α gene deletion or pharmacological inhibition disrupts LTP in CA1 of the hippocampus but elicits varying magnitudes of behavioral learning and memory deficits in mice. In particular, DAGL-α-/- mice display profound impairments in the Object Location assay and Morris Water Maze (MWM) acquisition engaging in nonspatial search strategies. In contrast, WT mice administered the DAGL-α inhibitor DO34 show delays in MWM acquisition and reversal learning, but no deficits in expression, extinction, forgetting, or perseveration processes in this task, as well as no impairment in Object Location. The deficits in synaptic plasticity and MWM performance occur in concert with decreased 2-AG and its major lipid metabolite (arachidonic acid), but increases of a 2-AG diacylglycerol precursor in hippocampus, PFC, striatum, and cerebellum. These novel behavioral and electrophysiological results implicate a direct and perhaps selective role of DAGL-α in the integration of new spatial information.SIGNIFICANCE STATEMENT Here we show that genetic deletion or pharmacologic inhibition of diacylglycerol lipase-α (DAGL-α) impairs hippocampal CA1 LTP, differentially disrupts spatial learning and memory performance in Morris water maze (MWM) and Object Location tasks, and alters brain levels of endocannabinoids and related lipids. Whereas DAGL-α-/- mice exhibit profound phenotypic spatial memory deficits, a DAGL inhibitor selectively impairs the integration of new information in MWM acquisition and reversal tasks, but not memory processes of expression, extinction, forgetting, or perseveration, and does not affect performance in the Objection Location task. The findings that constitutive or short-term DAGL-α disruption impairs learning and memory at electrophysiological and selective in vivo levels implicate this enzyme as playing a key role in the integration of new spatial information.

The Chylomicronemia Syndrome Is Most Often Multifactorial: A Narrative Review of Causes and Treatment.

The chylomicronemia syndrome occurs when triglyceride levels are severely elevated (usually >16.95 mmol/L [1500 mg/dL]) and is characterized by such clinical features as abdominal pain, acute pancreatitis, eruptive xanthomas, and lipemia retinalis. It may result from 1 of 3 conditions: the presence of secondary forms of hypertriglyceridemia concurrent with genetic causes of hypertriglyceridemia, termed multifactorial chylomicronemia syndrome (MFCS); a deficiency in the enzyme lipoprotein lipase and some associated proteins, termed familial chylomicronemia syndrome (FCS); or familial partial lipodystrophy. Most chylomicronemia syndrome cases are the result of MFCS; FCS is very rare. In all these conditions, triglyceride-rich lipoproteins accumulate because of impaired plasma clearance. This review describes the 3 major causes of the chylomicronemia syndrome; their consequences; and the approaches to treatment, which differ considerably by group.

Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue inflammation and liver steatosis in obese mice.

OBJECTIVE: Hypovitaminosis D is common in the obese population and patients suffering from obesity-associated disorders such as type 2 diabetes and fatty liver disease, resulting in suggestions for vitamin D supplementation as a potential therapeutic option. However, the pathomechanistic contribution of the vitamin D-vitamin D receptor (VDR) axis to metabolic disorders is largely unknown. METHODS: We analyzed the pathophysiological role of global and intestinal VDR signaling in diet-induced obesity (DIO) using global Vdr-/- mice and mice re-expressing an intestine-specific human VDR transgene in the Vdr deficient background (Vdr-/- hTg). RESULTS: Vdr-/- mice were protected from DIO, hepatosteatosis and metabolic inflammation in adipose tissue and liver. Furthermore, Vdr-/- mice displayed a decreased adipose tissue lipoprotein lipase (LPL) activity and a reduced capacity to harvest triglycerides from the circulation. Intriguingly, all these phenotypes were partially reversed in Vdr-/- hTg animals. This clearly suggested an intestine-based VDR activity on systemic lipid homeostasis. Scrutinizing this hypothesis, we identified the potent LPL inhibitor angiopoietin-like 4 (Angptl4) as a novel transcriptional target of VDR. CONCLUSION: Our study suggests a VDR-mediated metabolic cross-talk between gut and adipose tissue, which significantly contributes to systemic lipid homeostasis. These results have important implications for use of the intestinal VDR as a therapeutic target for obesity and associated disorders.

Tomato Juice Supplementation Influences the Gene Expression Related to Steatosis in Rats.

The objective of this work was to identify the effect of tomato juice on the expression of genes and levels of metabolites related to steatosis in rats. Male Sprague Dawley rats (8 weeks-old) were grouped (6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high-fat diet and water), and HL (high-fat diet and tomato juice). After an intervention period of 5 weeks, rats were sacrificed and biochemical parameters, biomarkers of oxidative stress, liver metabolites, and gene expression were determined. Although the H diet provoked dislipemia related to steatosis, no changes in isoprostanes or liver malondialdehyde (MDA) were observed. Changes in the gene expression of the HA group were produced by the high consumption of fat, whereas the consumption of tomato juice had different effects, depending on the diet. In the NL group, the genes involved in ß-oxidation were upregulated, and in groups NL and HL upregulation of CD36 and downregulation of APOB and LPL were observed. In addition, in the HL group the accumulation of lycopene upregulated the genes FXR and HNF4A, which have been suggested as preventive factors in relation to steatosis. Regarding the metabolomics study, intake of tomato juice stimulated the biosynthesis of glutathione and amino acids of the transulfurization pathway, increasing the levels of metabolites related to the antioxidant response.

Hypertriglyceridemia-induced pancreatitis: updated review of current treatment and preventive strategies.

Hypertriglyceridemia (HTG) is an uncommon but well-established cause of acute pancreatitis (AP) comprising up to 7% of the cases. The clinical course of HTG-induced pancreatitis (HTGP) is highly similar to that of AP of other etiologies with HTG being the only distinguishing clinical feature. However, HTGP is often correlated with higher severity and elevated complication rate. At present, no approved treatment guideline for the management of HTGP is available, although different treatment modalities such as insulin, heparin, fibric acids, and omega 3 fatty acids have been successfully implemented to reduce serum triglycerides (TG). Plasmapheresis has also been used to counteract elevated TG levels in HTGP patients. However, it has been associated with complications. Following the management of acute phase, lifestyle modifications including dietary adjustments and drug therapy are essential in the long-term management of HTGP and the prevention of its relapse. Results from studies of small patient groups describing treatment and prevention of HTGP are not sufficient to draw solid conclusions resulting in no treatment algorithm being available for effective management of HTGP. Therefore, prospective randomized, active-controlled clinical studies are required to find a better treatment regimen for the management of HTGP. Until date, one randomized clinical trial has been performed to compare clinical outcomes of different treatment approaches for HTGP. However, further studies are required to outline a generalized and efficient treatment regimen for the management of HTGP.

Restoring Effects of Natural Anti-Oxidant Quercetin on Cellular Senescent Human Dermal Fibroblasts.

The oxidative damage initiated by reactive oxygen species (ROS) is a major contributor to the functional decline and disability that characterizes aging. The anti-oxidant flavonoid, quercetin, is a plant polyphenol that may be beneficial for retarding the aging process. We examined the restoring properties of quercetin on human dermal fibroblasts (HDFs). Quercetin directly reduced either intracellular or extracellular ROS levels in aged HDFs. To find the aging-related target genes by quercetin, microarray analysis was performed and two up-regulated genes LPL and KCNE2 were identified. Silencing LPL increased the expression levels of senescence proteins such as p16INK4A and p53 and silencing KCNE2 reversed gene expressions of EGR1 and p-ERK in quercetin-treated aged HDFs. Silencing of LPL and KCNE2 decreased the expression levels of anti-oxidant enzymes such as superoxide dismutase and catalase. Also, the mitochondrial dysfunction in aged HDFs was ameliorated by quercetin treatment. Taken together, these results suggest that quercetin has restoring effect on the cellular senescence by down-regulation of senescence activities and up-regulation of the gene expressions of anti-oxidant enzymes in aged HDFs.

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets.

Anti-Obesity Effect of Allium hookeri Leaf Extract in High-Fat Diet-Fed Mice.

Allium hookeri has been widely cultivated and used as a vegetable and medicine in Asia, but its anti-obesity effects have not been previously reported. In this study, the effects of a leaf extract of A. hookeri on obesity were investigated by administering a high-fat diet (HFD) to mice. Male Institute of Cancer Research mice (n = 32; 5 weeks old) were randomly divided into four groups: normal-diet group, HFD group, HFD containing 200 mg/kg/day A. hookeri leaf extract (HFD-A1), and HFD containing 400 mg/kg/day A. hookeri leaf extract (HFD-A2). A. hookeri leaf extract was orally administered daily for 4 weeks. We found that the body weight gain and organ tissue weights of mice in the HFD-A1 and HFD-A2 groups were significantly lower compared with those of mice in the HFD group. Administration of A. hookeri leaf extract also significantly decreased the size of the epididymal adipose tissue (AT). Serum levels of triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, and the atherogenic index were significantly lower in the HFD-A1 and HFD-A2 groups than in the HFD group. The TG and total cholesterol levels in the hepatic, epididymal, and mesenteric ATs of the HFD-A2 group were significantly lower than the levels in the HFD group. In addition, mRNA levels of liver fatty acid synthase and lipoprotein lipase were decreased in the A. hookeri leaf extract groups compared with those of the HFD group. These results demonstrate that intake of A. hookeri leaf may have beneficial effects for suppressing obesity-related disease.

Microarray analysis of Longissimus thoracis muscle gene expressions in vitamin A-restricted Japanese Black steers in middle fattening stage.

Vitamin A (VA) restriction in beef cattle improves meat marbling; however, the underlying molecular mechanisms remain incompletely understood. We performed microarray analysis to clarify the effect of VA restriction on Longissimus thoracis gene expressions in Japanese Black steers. Six Japanese Black steers 13-14 months of age were divided into two groups: S group (n = 3), which received VA supplementation, and R group (n = 3), in which dietary VA intake was restricted. Steers were fattened for 7 months, following which tissue samples were obtained. Extracted RNA samples were analyzed by Affymetrix Genechip Bovine Genome Array. Lists of genes highly expressed in the R and S groups were obtained. The lists were functionally interpreted using functional annotation software, DAVID. In the R and S groups, 48 and 40 genes were significantly highly expressed, respectively. The gene list of the R group included CD36, LPL, GPAM, DGAT2, and SCD and additional genes annotated 'PPAR signaling pathway,' 'lipid biosynthesis' and 'mitochondrion,' whereas that of the S group included COL1A2, FN1 and DCN and additional genes annotated 'extracellular matrix.' Changes in the expression of these genes are possibly involved in marbling improvement in beef cattle by VA restriction.

Dietary phosphatidylcholine impacts on growth performance and lipid metabolism in adult Genetically Improved Farmed Tilapia (GIFT) strain of Nile tilapia Oreochromis niloticus.

This study aimed to determine the effects of supplementing the diet of adult Nile tilapia Oreochromis niloticus with phosphatidylcholine (PC) on growth performance, body composition, fatty acid composition and gene expression. Genetically Improved Farmed Tilapia fish with an initial body weight of 83·1 (sd 2·9) g were divided into six groups. Each group was hand-fed a semi-purified diet containing 1·7 (control diet), 4·0, 6·5, 11·5, 21·3 or 41·0 g PC/kg diet for 68 d. Supplemental PC improved the feed efficiency rate, which was highest in the 11·5 g PC/kg diet. Weight gain and specific growth rate were unaffected. Dietary PC increased PC content in the liver and decreased crude fat content in the liver, viscera and body. SFA and MUFA increased and PUFA decreased in muscle with increasing dietary PC. Cytoplasmic phospholipase A 2 and secreted phospholipase A 2 mRNA expression were up-regulated in the brain and heart in PC-supplemented fish. PC reduced fatty acid synthase mRNA expression in the liver and visceral tissue but increased expression in muscle. Hormone-sensitive lipase and lipoprotein lipase expression increased in the liver with increasing dietary PC. Growth hormone mRNA expression was reduced in the brain and insulin-like growth factor-1 mRNA expression in liver reduced with PC above 6·5 g/kg. Our results demonstrate that dietary supplementation with PC improves feed efficiency and reduces liver fat in adult Nile tilapia, without increasing weight gain, representing a novel dietary approach to reduce feed requirements and improve the health of Nile tilapia.

Regulation of hepatic lipid deposition by phospholipid in large yellow croaker.

Dietary phospholipid (PL) supplementation has been shown to reduce lipid accumulation in the tissues of farmed fish; however, the mechanisms underlying this effect are largely unknown. Thus, the present study was conducted to evaluate the potential impacts of PL on hepatic lipid metabolism both in vivo and in vitro. For in vivo study, four experimental diets - low lipid and low PL diet, as control diet (LL-LP diet, containing 12 % lipid and 1·5 % PL), low-lipid and high-PL diet (containing 12 % lipid and 8 % PL), high-lipid and low-PL diet (HL-LP diet, containing 20 % lipid and 1·5 % PL) and high-lipid and high-PL diet (HL-HP diet, containing 20 % lipid and 8 % PL) - were randomly allocated to four groups of large yellow croaker (Larimichthys crocea) (three cages per group) with similar initial body weight (approximately 8 g). For in vitro study, primary hepatocytes isolated from large yellow croaker were incubated either with graded levels of phosphatidylcholine (PC) (0-250 µm) or small interfering RNA (siRNA) for CTP: choline phosphate cytidylyltranferase α (CCTα) (siRNA-CCTα). Results showed that survival was independent of dietary treatments (P>0·05). Weight gain and feed efficiency in the HL-HP group were significantly higher than in the LL-LP and HL-LP groups (P<0·05). High level of dietary PL could markedly reduce abnormal hepatic lipid accumulation induced by the HL-LP diet (P<0·05). Similarly, compared with the corresponding controls, a significant decrease/increase in lipid content was observed in primary hepatocytes incubated with PC/siRNA-CCTα (P<0·05). High level of dietary PL reversed the HL-LP diet-induced increased levels of mRNA of fatty acid uptake and lipid synthesis related genes (P<0·05). In addition, High level of dietary PL markedly down-regulated the transcript levels of fatty acid oxidation-related genes and enhanced the transcript levels of VLDL assembly-related genes regardless of dietary lipid levels (P<0·05). Compared with corresponding controls, primary hepatocytes treated with PC showed significantly higher mRNA expression of lipid synthesis and VLDL assembly-related genes and lower mRNA expression of fatty acid oxidation-related genes, with hepatocytes treated with siRNA-CCTα exhibiting the opposite trend (P<0·05). In summary, these results demonstrated that high level of dietary PL might reverse the HL-LP diet-induced abnormal lipid accumulation in the liver through inhibiting fatty acid uptake and lipid synthesis, together with promoting the lipid export at the transcriptional level. Lipid export-promoting effect of PC was confirmed by in vitro studies. The present study showed for the first time that PL or PC could influence various metabolic pathways to regulate hepatic lipid deposition in fish at least at the transcriptional level.

[Effects of Mori Folium extract on diet-induced obesity mechanism in rats].

To study the anti-obesity effect of Mori Folium extract on diet-induced obesity(DIO) and to explore the preliminary mechanism in rats. DIO rat models were established by high glucose and high fat diet for 8 weeks. Then high(10 mg•kg⁻¹) and low(5 mg•kg⁻¹) does Mori Folium extracts were given by intragastric administration for 13 weeks. After the last administration, their body weight, 24 h food intake, water intake, Lee's index, liver/body mass index, and fat/body mass index were determined. The levels of lipoprotein lipase(LPL), CCAAT/enhancer-binding protein alpha(C/EBPα) and peroxisome proliferator-activated receptor gamma(PPARγ) were measured by enzyme-linked immunosorbent assay(ELISA). Phosphorylated AMP-activated protein kinase alpha(p-AMPKα), C/EBPα and PPARγ expression levels in adipose tissues were detected by Western blot. The hematoxylin-eosin staining(HE) was used to observe the histopathological changes of adipose tissues. The results showed that both high dose and low dose Mori Folium extract can decrease body weight, Lee's index, renal fat/body mass ratio and testicle fat/body mass ratio, and the high dose group could decrease the total fat/body mass ratio. Both high dose and low dose groups had no significant effect on the food intake and water intake; however, they could decrease levels of LPL in fat, up-regulate p-AMPKα protein expression, down-regulate C/EBPα and PPARγ protein expression, and reduce fat cell volume. In conclusion, Mori Folium extract had a slimming effect on DIO rats, and its mechanism may be associated with up-regulating the expression of p-AMPKα, down-regulating the expression of PPARγ, C/EBPα and LPL, inhibiting the differentiation of preadipocytes into mature fat cells, and reducing the volume of fat cells.