Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism

The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.     

Molecular characterization of microtubule-associated protein 1-light chain 3B in <Emphasis Type="Italic">Megalobrama amblycephala</Emphasis> fed with high fat/berberine diets

This study tested the effect of berberine on autophagy-related protein of Megalobrama amblycephala fed with high fat diet under different feeding modes. The full-length complementary DNA (cDNA) of microtubule-associated protein 1-light chain 3B (LC3B) was 1871 bp with an open reading frame of 378 bp encoding 125 amino acids. High homology at nucleotide and amino acid sequences to carp LC3B was revealed though sequence analysis. LC3B was mainly (P?< 0.05) expressed in hepatopancreas but lower in several peripheral tissues, including gill, intestine, kidney, and spleen. The fish (average initial weight 4.70?±?0.02 g) were fed with eight experiment diets containing two lipid levels (5 and 10%) or four berberine-feeding modes (without berberine, supplementing 50 mg/kg berberine at 2-week intervals, 4-week intervals, or continuous) for 8 weeks. The results showed that the numbers of autophagosomes and hepatopancreas LC3B messenger RNA (mRNA) expression levels were significantly (P?< 0.05) affected both by dietary lipid level and beberine feeding mode, and the highest (P?<?0.05) numbers of autophagosomes and LC3B expression levels were observed in fish at berberine continuous feeding mode groups. The findings may provide the molecular mechanisms underlying lipid metabolism and immune effect of berberine, which was associated with enhanced autophagy in fish.     

Inhibition of Cannabinoid Receptor 1 Can Influence the Lipid Metabolism in Mice with Diet-Induced Obesity

A growing number of evidences accumulated about critical metabolic role of cannabinoid type 1 receptor (CB1), carnitine palmitoyltransferase-1 (CPT1) and peroxisome proliferator-activated receptors (PPARs) in some peripheral tissues, including adipose tissue, liver, skeletal muscle and heart. To better understand the interactions of CB1, CPT1 and PPARs in these tissues, 30 diet-induced obese (DIO) C57BL/6J male mice were obtained, weight-matched and divided into two groups (15 in each group): (i) DIO/vehicle mice (D-Veh) and (ii) DIO/SR141716 mice (D-SR) treated with SR141716 (or rimonabant, a selective CB1 receptor blocker) administered orally (10 mg/kg daily). Another 15 mice fed standard diet (STD) formed the STD/vehicle group (S-Veh). At the end of 3-week treatment, mean body weight was 28.4 ± 0.5, 36.5 ± 0.8, and 30.3 ± 1.2 g for the S-Veh, D-Veh, and D-SR group, respectively (p < 0.05; D-Veh vs. D-SR). Liver weight in the D-SR group was also decreased significantly compared to the D-Veh group (p < 0.05). Serum levels of total cholesterol, high-density lipoprotein cholesterol, leptin and adiponectin in the D-SR group were ameliorated compared to the D-Veh group (p < 0.05). Both qRT-PCR and Western blot assay revealed that CB1 expression levels were efficiently blocked by SR141716 in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), skeletal muscles and liver (D-SR vs. D-Veh; p < 0.05), whereas there was no significant difference between S-Veh and D-Veh mice (p > 0.05). Simultaneously with the reduction of CB1 expression in the D-SR group, the expression levels of CPT1A isoform (protein) in the liver and heart and CPT1B isoform (protein) in the SAT, VAT, liver and skeletal muscles were significantly increased (p < 0.05; D-SR vs. D-Veh). Interestingly, the CPT1A and CPT1B expression levels in heart were detected slightly. The expression levels of PPARα in the SAT, VAT, liver and skeletal muscles and PPARγ in the SAT and skeletal muscles in the D-SR group were significantly increased compared to the D-Veh mice (p < 0.05). However, the PPARβ expression level differed from that of PPARα and PPARγ. Taken together, these data indicate that the inhibition of CB1 could ameliorate lipid metabolism via the stimulation of the CPT1A and CPT1B expression in vivo. Simultaneously, the PPARα and PPARγ expression levels significantly differed compared to that of PPARβ in obesity and lipid metabolism-related disorders under blockade of CB1. Both the mechanism of the influence of CB1 inhibition on lipid metabolism in the examined tissues and the specific mechanism of PPARα, PPARγ and PPARβ involvement in lipid exchange under these conditions remain to be further elucidated.     

Inhibition of the actions of peroxisome proliferator-activated receptor alpha on obesity by estrogen

Objective: To determine whether the major ovarian factor estrogen modulates peroxisome proliferator‐activated receptor (PPAR) α actions on obesity and to investigate the mechanism by which estrogen regulates PPARα actions. Research Methods and Procedures: Female ovariectomized mice were randomly divided into four groups (n = 8/group). After they were treated with combinations of high fat, fenofibrate (FF), or 17β‐estradiol (E) for 13 weeks, variables and determinants of obesity and lipid metabolism were measured using in vivo and in vitro approaches. Results: When female ovariectomized mice were given a high‐fat diet with either FF or E, body weight gain and white adipose tissue mass were significantly reduced and serum lipid profiles were improved compared with control mice fed a high‐fat diet alone. When mice were concomitantly treated with FF and E, however, E reversed the effects of FF on body weight gain, serum lipid profiles, and hepatic PPARα target gene expression. Consistent with the in vivo data, E not only decreased basal levels of PPARα reporter gene activation but also significantly decreased Wy14,643‐induced luciferase reporter activity. In addition, inhibition of PPARα functions by E did not seem to occur by interfering with the DNA binding of PPARα. Discussion: Our results demonstrate that in vivo and in vitro treatment of estrogen inhibited the actions of FF‐activated PPARα on obesity and lipid metabolism through changes in the expression of PPARα target genes, providing evidence that FF does not regulate obesity in female mice with functioning ovaries.     

Exercise training decreases plasma leptin levels and the expression of hepatic leptin receptor-a, -b, and, -e in rats

In addition to acting in the central nervous system, leptin also acts on peripheral tissues such as liver to provide a protection against lipid accretion. Previous evidence from human and animal model indicates that exercise training reduces circulating leptin levels beyond the changes in adiposity levels. Because liver is one of the main peripheral organs for leptin action, this present study was designed to determine whether leptin receptors expression in liver is changed by exercise training. Female rats trained (TR) or kept sedentary (Sed) for 8 weeks were submitted either to a standard (SD) diet for 8 weeks or for 6 weeks followed by 2 weeks of high-fat (HF) or high-carbohydrate (HC) feeding. Food intake, adiposity levels, circulating plasma leptin and insulin concentrations along with the hepatic expression of leptin receptors (ObR-a, -b, and -e) and peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α), were measured in all the animals. Intra-abdominal fat depots were increased under the HF but not under the HC diet. As expected, exercise training decreases intra-abdominal adiposity in animals fed with the SD and the HF diet, and to a lesser extent in HC-fed rats. Plasma leptin levels either expressed in absolute values or in values relative to adiposity levels were significantly (P < 0.05) increased with the HF diet and significantly decreased in TR animals, independently of the diet. Moreover, a significant (P < 0.01) reduction in hepatic gene expression of ObR-a, -b and -e was found in TR animals in all the three diet conditions. PPARα and PGC-1α mRNAs were also decreased (P < 0.05) in TR animals in two out of three diet conditions. The present findings indicate that exercise training-induced decrease in plasma leptin levels is accompanied by a reduction in gene expression of three different isoforms of leptin receptors in liver.     

Changes in Immunity,Expression of some Immune-Related Genes of Shabot Fish, <Emphasis Type="Italic">Tor grypus</Emphasis>, Following Experimental Infection with <Emphasis Type="Italic">Aeromonas hydrophila</Emphasis>: Effects of Autochthonous Probiotics

In this study, the effects of orally administrated two native probiotics (Lactobacillus plantarum and Lactobacillus delbrueckii ssp. bulguricus), isolated from the intestine of Shabot fish, Tor grypus, on some immune response parameters and immune-related genes expression against Aeromonas hydrophila in T. grypus were evaluated. Four hundred and eighty juveniles weighing 45?±?10 g were randomly divided into four groups (with three replications) and fed with the experimental diet containing 5?×?10⁷ cfu g^?1 of L. plantarum (G1), Lactobacillus bulgaricus (G2), Lactobacillus casei (G3), and a control diet (without probiotics) for 60 continuous days. At the end of the dietary treatments, fish were challenged with a lethal concentration of A. hydrophila (5?×?10⁸ CFU ml^?1) via intra peritoneal (i.p) injection. Blood and head kidney samples were taken from six fish in each treatment before challenging and 6, 12, 24, and 48 h and also 7 days after injection. The results showed that lysozyme, complement, bactericidal, and NBT activity of probiotic-treated groups were significantly elevated (P?<?0.05). The IL-8, IL-1β, and TNF-α gene expressions were significantly higher in all probiotic-treated groups (P?<?0.05). Meanwhile, a high direct correlation was observed between serum immune parameters and expression of immune-related genes (P?<?0.0001); furthermore, the highest correlation (R ²?=?0.634, P?<?0.0001) was recorded between IL-1β expression and NBT activity. It can be concluded that not only two native probiotics strains stimulate serum immune responses parameters and immune-related gene expression in T. grypus, but also a high correlation was seen among these indices. The study suggests that gastrointestinal colonization is preferred for host specificity as the strain previously derived from shabot fish displayed better colonization than the non-indigenous bacteria strain such as L. casei. Therefore, these native probiotics bacteria can be accounted as suitable candidates to immune stimulation in fish.     

Lipid metabolism in adipose tissue and liver from diet-induced obese rats: a comparison between <Emphasis Type="Italic">Wistar</Emphasis> and <Emphasis Type="Italic">Sprague-Dawley</Emphasis> strains

Some researchers have proposed important variations in adipose tissue among different strains of rats and mice in response to a high-caloric (hc) diet, but data concerning the mechanisms underlying these differences are scarce. The aim of the present research was to characterize different aspects of triacylglycerol (TG) metabolism and clock genes between Sprague-Dawley and Wistar rats. For this purpose, 16 male Sprague-Dawley and 16 male Wistar rats were divided into four experimental groups (n?=?8) and fed either a normal-caloric (nc) diet or a hc diet for 6 weeks. After sacrifice, liver and epididymal, perirenal, mesenteric, and subcutaneous adipose tissue depots were dissected, weighed and immediately frozen. Liver TG content was quantified, RNA extracted for gene expression analysis and fatty acid synthase enzyme activity measured. Two-way ANOVA and Student’s t test were used to perform the statistical analyses. Under hc feeding conditions, Wistar rats were more prone to fat accumulation in adipose tissue, especially in the epididymal fat depot, due to their increased lipogenesis and fatty acid uptake. By contrast, both strains of rats showed similarly fatty livers after hc feeding. Peripheral clock machinery seems to be a potential explanatory mechanism for Wistar and Sprague-Dawley strain differences. In conclusion, Wistar strain seems to be the best choice as animal model in dietary-induced obesity studies.     

Fermented Soybean Meal Increases Lactic Acid Bacteria in Gut Microbiota of Atlantic Salmon (<Emphasis Type="Italic">Salmo salar</Emphasis>)

The main goal of the present study was to address the effect of feeding fermented soybean meal-based diet to Atlantic salmon on gut microbiota. Further, expression of genes of interest, including cathelicidin antimicrobial peptide (cath), mucin 2 (muc2), aquaporin (aqp8ab), and proliferating cell nuclear antigen (pcna), in proximal intestine of fish fed either experimental diet was analyzed. Three experimental diets, including a control fishmeal (30% FM), soybean meal (30% SBM), or fermented soybean meal diet (30% FSBM) were randomly assigned to triplicate tanks during a 50-day trial. The PCR-TTGE showed microbiota composition was influenced by experimental diets. Bands corresponding to genus Lactobacillus and Pediococcus were characteristic in fish fed the FSBM-based diet. On the other hand, bands corresponding to Isoptericola, Cellulomonas, and Clostridium sensu stricto were only observed in fish FM-based diet, while Acinetobacter and Altererythrobacter were detected in fish fed SBM-based diet. The expression of muc2 and aqp8ab were significantly greater in fish fed the FSBM-based diet compared with the control group. Our results suggest feeding FSBM to Atlantic salmon may (1) boost health and growth physiology in fish by promoting intestinal lactic acid bacteria growth, having a prebiotic-like effect, (2) promote proximal intestine health by increasing mucin production, and (3) boost intestinal trans-cellular uptake of water. Further research to better understands the effects of bioactive compounds derived from the fermentation process of plant feedstuff on gut microbiota and the effects on health and growth in fish is required.     

Dietary Administration of <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> Enhanced Growth Performance and Innate Immune Response of Siberian Sturgeon, <Emphasis Type="Italic">Acipenser baerii</Emphasis>

We investigated the effects of Lactobacillus plantarum used as a dietary supplement on the growth performance and innate immune response in juvenile Siberian sturgeon Acipenser baerii. Juvenile fish (14.6 ± 2.3 g) were fed three experimental diets prepared by supplementing a basal diet with L. plantarum at different concentrations [1 × 10⁷, 1 × 10⁸ and 1 × 10⁹ colony-forming units (cfu) g^?1] and a control (non-supplemented basal) diet for 8 weeks. Growth performance indices were increased in fish fed the 1 × 10⁸ cfu g^?1 L. plantarum diet compared to the other groups. There was an increased innate immune response in fish fed the experimental diets. The highest levels of lysozyme activity, total immunoglobulin (IgM) and complement component 3 (C3) were observed in fish fed the diet containing L. plantarum at a concentration of 1 × 10⁸ cfu g^?1, but there was no significant difference in the level of complement component 4 (C4) in fish fed the experimental diets or the control diet. The present study underlying some positive effects (growth performance and immune indices) of dietary administration of L. plantarum at a concentration of 1 × 10⁸ cfu g^?1 in the Siberian sturgeon.     

Pigs fed saturated fat/cholesterol have a blunted hypothalamic-pituitary-adrenal function,are insulin resistant and have decreased expression of IRS-1, PGC1α and PPARα

The increasing incidence of insulin resistance has been linked to both increased intake of saturated fatty acids and disruption of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypothesis that adding saturated fat/cholesterol to the diet of growing pigs would both disrupt HPA function and cause insulin resistance. Three-month-old pigs were fed either a control (13% energy from fat) or a high saturated fatty acid cholesterol (HSFC) diet (44% energy from fat; 2% cholesterol). After 10 weeks on the diets, intravenous ACTH, insulin and glucose challenges were performed, and after 12 weeks, tissue samples were taken for measurement of mRNA and for lipid-rich aortic lesions. Plasma total, HDL- and LDL-cholesterol were significantly increased in pigs fed the HSFC diet. Cortisol release during the ACTH challenge was suppressed in HSFC-fed pigs which were also more insulin resistant and glucose intolerant than controls. The HSFC diet decreased the expression of insulin receptor (IR) and insulin receptor substrate-1 in muscle and adipose tissue as well as adiponectin and adiponectin receptor 2 expression in fat. The HSFC diet decreased PGC-1α and PPARα expression in muscle but increased PPARα expression in liver. There was a trend for an increase in lipid-stained lesion frequency around the abdominal branches of the aorta in HSFC-fed pigs. We conclude that feeding increased saturated fat to pigs causes disruption in the HPA axis, insulin resistance and decreased muscle and adipose expression of genes controlling insulin signalling and mitochondrial oxidative capacity.     

Changes in cardiac Na<Superscript>+</Superscript>/K<Superscript>+</Superscript>-ATPase expression and activity in female rats fed a high-fat diet

The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na⁺/K⁺-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150–200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the α₁ subunit of Na⁺/K⁺-ATPase by 30% (p < 0.05), expression of total α₁ subunit of Na⁺/K⁺-ATPase by 31% (p < 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p < 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p < 0.01) and 62% (p < 0.05), respectively. Our results suggest that a HF diet alters cardiac Na⁺/K⁺-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats.     

Rosiglitazone and fenofibrate improve insulin sensitivity of pre-diabetic OLETF rats by reducing malonyl-CoA levels in the liver and skeletal muscle

AimsRosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-γ (PPARγ) and -α (PPARα), respectively, improve insulin sensitivity in diabetic animals and in patients with type 2 diabetes. Here we investigated how pre-diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats fed with normal and high-fat diets respond to these PPAR agonists.Main methodsPre-diabetic OLETF rats were subjected to high-fat or standard diets with or without rosiglitazone or fenofibrate for 2 weeks. The metabolism of the rats and the levels of malonyl-CoA and activities of malonyl-CoA decarboxylase (MCD), acetyl-CoA carboxylase (ACC), and AMP-activated protein kinase (AMPK) in metabolic tissues were assessed.Key findingsRosiglitazone and fenofibrate significantly improved insulin sensitivity and reduced the levels of plasma triglycerides and free fatty acids in OLETF rats fed with a high-fat diet. Fenofibrate particularly reduced the body weight, fat, and total cholesterol in high fat diet OLETF rats. The highly elevated malonyl-CoA levels in the skeletal muscle and liver of OLETF rat were significantly reduced by rosiglitazone or fenofibrate due to, in part, the increased MCD activities and expression. On the other hand, ACC activities were unchanged in skeletal muscle and decreased in liver in high fat diet group. AMPK activities were dramatically decreased in OLETF rats and not affected by these agonists.SignificanceThese results demonstrate that treatment of pre-diabetic OLETF rats–particularly those fed a high-fat diet–with rosiglitazone and fenofibrate significantly improves insulin sensitivity and fatty acid metabolism by increasing the activity of MCD and reducing malonyl-CoA levels in the liver and skeletal muscle.     

Hemato-Immunological Responses and Disease Resistance in Siberian Sturgeon <Emphasis Type="Italic">Acipenser baerii</Emphasis> Fed on a Supplemented Diet of <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis>

A feeding trial was conducted to investigate the effects of different levels of dietary Lactobacillus plantarum on hemato-immunological parameters and resistance against Streptococcus iniae infection in juvenile Siberian sturgeon Acipenser baerii. Fish (14.6 ± 2.3 g) were fed three experimental diets prepared by supplementing a basal diet with L. plantarum at different concentrations [1 × 10⁷, 1 × 10⁸ and 1 × 10⁹ colony-forming units (cfu) g^?1] and a control (non-supplemented basal) diet for 8 weeks. Innate immune responses (immunoglobulin (Ig), alternative complement activity (ACH50) and lysozyme activity) were significantly higher in fish fed the 1 × 10⁸ and 1 × 10⁹ cfu g^?1 L. plantarum diet compared to the other groups (P < 0.05). Furthermore, fish fed on various levels of L. plantarum significantly showed higher red blood cell (RBC), hemoglobin (Hb), white blood cell (WBC) and monocyte compared to those of the control group (P < 0.05). At the end of the feeding experiment, some fish were challenged with S. iniae to quantify the level of disease resistance. The mortality after S. iniae challenge was decreased in fish fed a probiotic. These results indicated that dietary supplementation of L. plantarum improved immune response and disease resistance of Siberian sturgeon juvenile.     

Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.     

Adipose Triglyceride Lipase (ATGL) Clone, Expression Pattern, and Regulation by Different Lipid Sources and Lipid Levels in Large Yellow Croaker (Pseudosciaena crocea R.)

Adipose triglyceride lipase (ATGL) was recently identified as a triglyceride (TG)-specific lipase. In this study, we first obtained from large yellow croaker fish a 1,820-bp (GenBank ID: HQ916211) ATGL cDNA fragment with a 141-bp 5′UTR, a 1,485-bp open reading frame, and a 194-bp 3′UTR. The predicted fish ATGL had 494 amino acids (GenBank ID: ADY89608) and a calculated molecular weight of 55.1 kDa. ATGL was highly expressed in liver and, to a lesser degree, in heart, muscle, and abdominal fat. ATGL gene expression was high at 4.5 g and then decreased at 157.9 g and increased again at 474.2 g. The effects of lipid levels and lipid sources on ATGL expression in vivo were also investigated. A high-lipid diet decreased ATGL expression in fish significantly (P?<?0.01). Fish in soybean oil group exhibited significantly lower ATGL expression than fish in the fish oil and beef tallow groups (P?<?0.01). These data enhance our understanding of ATGL in fish lipid metabolism.     

Dietary fish oil reduces systemic inflammation and ameliorates sepsis-induced liver injury by up-regulating the peroxisome proliferator-activated receptor gamma-mediated pathway in septic mice

This study investigated the effect of dietary fish oil on systemic inflammation and hepatic injury in mice with polymicrobial sepsis. Male ICR mice were assigned to a control group (C, n=30) and a fish oil group (FO, n=30). Mice in the C group were fed a semi-purified diet with 10% soybean oil, and those in the FO group were fed a fish oil diet (2.5% fish oil+7.5% soybean oil; w/w). Three weeks later, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed at 0, 6 and 24 h after CLP, respectively. Results showed that compared with C group, the FO group had lower plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nitrite at 6 and 24 h after CLP. Also, peritoneal lavage fluid concentrations of TNF-α and prostaglandin (PG) E2 were significantly lower at 24 h in the FO than in the C group. The FO group had lower myeloperoxidase activities at 6 h after CLP in various organs. Plasma aminotransferase and alanine aminotransferase activities revealed significantly decreased in the FO group. The DNA-binding activity of peroxisome proliferators-activated receptor gamma (PPARγ) and mRNA expression of I kappaB alpha (IκBα) were up-regulated while nuclear factor (NF)-κB p65 DNA-binding activity, inducible nitric oxide synthase protein expression and the concentration of nitrotyrosine were significantly decreased in the FO group in liver after CLP. These results indicate that dietary fish oil administration may attenuate systemic inflammation and up-regulate hepatic PPARγ DNA-binding activity, which may consequently have ameliorated liver injury in these septic mice.     

<Emphasis Type="Italic">Agaricus bisporus</Emphasis> supplementation reduces high-fat diet-induced body weight gain and fatty liver development

Obesity is a global epidemic characterized not only by excessive fat deposition but also by important complications such as nonalcoholic liver steatosis. Beneficial antiobesogenic effects have been described for some mushrooms. The current study aimed to demonstrate the protective effect of Agaricus bisporus (AB) supplementation against the metabolic alterations induced by high-fat-diet (HFD) feeding. Eight-week-old C57BL/6J mice were fed for 10 weeks with one of the following diets: (1) control diet (n?=?7), (2) HFD (n?=?7), (3) HFD supplemented with 5% AB (n?=?9), and (4) HFD supplemented with 10% AB (n?=?9). A pair-fed group was also included for the 10% AB group (n?=?6). The impact of AB supplementation on food intake, body weight gain, and liver and fat pad weights was examined. Biochemical, histological, and molecular parameters were also analyzed. Dietary supplementation with 10% AB reduced the HFD-induced increase in body, epididymal, and mesenteric fat weights (p?<?0.01, p?<?0.05, and p?<?0.05, respectively). Supplementation with AB also reduced liver damage in a dose-dependent manner (p?<?0.01 and p?<?0.001). This effect was confirmed by histological analysis that showed that liver steatosis was markedly reduced in mice fed with AB. The beneficial properties of 10% AB supplementation appear to be mediated through a decrease in food intake and via stimulation of mesenteric and hepatic free-fatty acid beta-oxidation, along with a decrease in epidydimal and hepatic expression of CD36. In conclusion, supplementation with AB prevents excessive body weight gain and liver steatosis induced by HFD consumption.     

PPARα is essential for retinal lipid metabolism and neuronal survival

Background

Peroxisome proliferator activated receptor-alpha (PPARα) is a ubiquitously expressed nuclear receptor. The role of endogenous PPARα in retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest energy-consuming cells in the body, requiring abundant energy substrates. PPARα is a known regulator of lipid metabolism, and we hypothesized that it may regulate lipid use for oxidative phosphorylation in energetically demanding retinal neurons.

Results

We found that endogenous PPARα is essential for the maintenance and survival of retinal neurons, with Pparα ^-/- mice developing retinal degeneration first detected at 8 weeks of age. Using extracellular flux analysis, we identified that PPARα mediates retinal utilization of lipids as an energy substrate, and that ablation of PPARα ultimately results in retinal bioenergetic deficiency and neurodegeneration. This may be due to PPARα regulation of lipid transporters, which facilitate the internalization of fatty acids into cell membranes and mitochondria for oxidation and ATP production.

Conclusion

We identify an endogenous role for PPARα in retinal neuronal survival and lipid metabolism, and furthermore underscore the importance of fatty acid oxidation in photoreceptor survival. We also suggest PPARα as a putative therapeutic target for age-related macular degeneration, which may be due in part to decreased mitochondrial efficiency and subsequent energetic deficits.