Proliferator-activated Receptor Alpha Research Articles

Influences of dietary sodium butyrate on growth, digestion, antioxidant capacity and health in juvenile Onychostoma macrolepis fed on high-fat diet

Butyrate is a short-chain fatty acid with growth and immune regulatory effects. The aim of this experiment was to investigate the effect of sodium butyrate (SB) on Onychostoma macrolepis fed high-fat diet. O.macrolepis (2.5 ± 0.1 g) were kept in twelve aquariums (three aquarium /treatment, fifteen fish / aquarium), fed a high-fat diet (control), and high-fat diet supplemented with 0.1%, 0.2% or 0.4% SB for fifty-six days. The results showed that the supplementation of 0.2% SB in high-fat diet significantly promoted the growth of O.macrolepis. Simultaneously, dietary SB supplementation improved lipase and trypsin activities and intestinal histological morphology of O.macrolepis consuming with high-fat diets. Furthermore, the supplementation of 0.2% or 0.4% SB in the diet enhanced serum immunity and intestinal antioxidant capacity. Additionally, the addition of 0.2–0.4% SB up-regulated the transcriptional level of peroxisome proliferators-activated receptor alpha (pparα) gene, thereby activating pparα-mediated β-oxidation and mitigating liver lipid accumulation of O.macrolepis. In summary, the addition of 0.2–0.4% SB in high-fat diet was beneficial to growth, digestion, immunity and health of O.macrolepis. This study provides a reference for SB as a functional additive of aquatic feed.

Evaluation of Anti-aging Effects of Gemfibrozil on D-galactose induced Aging Mouse Model

Background: Aging is the sequential or progressive changes in the organisms that is associated with increasing susceptibility to disease and death. Advanced age is associated with increased incidence of a variety of chronic disease states that share oxidative stress and inflammation as causative role players. Accumulating evidence in published literature showed that the use of antioxidant and anti-inflammatory agents is an effective approach to alleviate or reverse aging-related changes with consequent reduction of the aging rate and related disease. Gemfibrozil, as a peroxisome proliferator-activated alpha receptor ligand (PPARα), is reported to have antioxidant and inflammatory activity. Aim of the study: Evaluate the anti-aging effect of gemfibrozil on many parameters associated with the aging process on the D-galactose induced aging mice model. Method: The current work was an experimental randomized controlled study in which 60 albino male mice weighing between 25 to 40 gm were randomly divided into 6 groups (10 mice each group). group1 apparently healthy group, receive normal saline orally. Group 2 (age induction group receive D-galactose 500 mg/kg) orally only for 6 weeks, group 3 (+D-galactose 500 mg/kg + vitc 100 mg/kg orally for 6 weeks) group 4 (D-galactose 500 mg/kg for 6 weeks then vitc 100 mg/kg for another 6 consecutive weeks group 5 (D-galactose 500 mg/kg + gemfibrozil 7.5 mg/kg concomitantly for 6 weeks) group 6 (D-galactose 500 mg/kg for 6 weeks then gemfibrozil 7.5 mg/kg for another 6 consecutive weeks. Then animals were sacrificed, liver and kidney were weighed for organ index measurement and tissue sections and heart homogenate were prepared for ELISA assay (measurement of TN alpha, IL1beta, SOD, GPX) and histopathological analysis of myocardial tissue. Results: results showed a significant rise in liver and kidney indices in animals that received gemfibrozil orally administered (during and after induction) compared to aged group, with a dramatic decrease in inflammatory and oxidative stress mediator level and a marked reversal effect on myocardial hypertrophy induced by D-galactose. Conclusion: Gemfibrozil oral administration alleviates aging-associated atrophic changes in liver and kidney, oxidative stress and inflammatory state in myocardial tissue and reverses aging-related myocardial hypertrophic changes.

First Insights on the Administration of Insect Oil (Black Soldier Fly Larvae) in the Diet of Juvenile Onychostoma macrolepis.

The use of insect products in aquatic feed is the focus of the aquaculture industry. Black soldier fly larvae oil (BSFLO) has been examined as a potential lipid source for diets for some fish species, but its utilization on Onychostoma macrolepis has not been explored. The influences of substituting fish oil (FO) with BSFLO in the diet on growth, biological indicators, approximate composition, serum biochemistry, antioxidant capacity and expression of lipid metabolism genes in juvenile O. macrolepis were investigated in an eight-week feeding experiment. Four experimental diets were prepared by replacing 0 (control), 25% (BSFLO-25), 50% (BSFLO-50) and 100% (BSFLO-100) FO with BSFLO, and then randomly assigned to twelve aquariums with ten fish (1.75 ± 0.05 g) in each aquarium. The findings showed that the growth indicators, body composition and serum biochemistry in the BSFLO-25 and BSFLO-50 groups had no statistical differences from those of the control group. The activities of superoxide dismutase (SOD) (91.22-94.96 U/mgprot) and the contents of malondialdehyde (MDA) (1.12-1.16 nmol/mgprot) in the liver appeared to be significantly the highest and the lowest in the BSFLO-25, BSFLO-50 and BSFLO-100 groups (p < 0.05). The adipocyte size and intraperitoneal fat index value of fish fed on the BSFLO-100 diet were significantly decreased compared to the control group (p < 0.05). The expression levels of lipid catabolism genes pparα, (peroxisome proliferators-activated receptor alpha) and cpt1a (carnitine palmitoyltransferase 1 isoform a) in the BSFLO-100 group were significantly higher than those of the control group (p < 0.05). The above results indicated that it was feasible to replace 25-50% dietary FO with BSFLO in juvenile O. macrolepis. Dietary BSFLO supplementation could enhance the antioxidant capacity of the liver and suppress intraperitoneal fat accumulation in O. macrolepis. The use of other insect oils in the diets of this species will be evaluated in future research.

Evaluation of cottonseed oil as a substitute for dietary fish oil of juvenile black seabream (Acanthopagrus schlegelii): Based on growth, lipid metabolism, antioxidant capacity and pi3k/akt pathway

An eight weeks feeding trial was conducted to evaluate the potential of cottonseed oil (CSO) as a substitute for fish oil (FO) on juvenile black seabream (Acanthopagrus schlegelii) (2.29 ± 0.01 g). Five diets were formulated with pure FO (FO) or partial CSO replacement of FO: 20% CSO (CSO20), 40% CSO (CSO40), 60% CSO (CSO60) and 80% CSO (CSO80), respectively. Results showed that fish fed CSO60 diet significantly increased growth performance compared to control group. Hepatic expression of genes related to long-chain polyunsaturated fatty acid biosynthesis were significantly up-regulated by dietary CSO60 compared to FO group. Hepatic paraffin section and serum biochemical indices showed that fish fed dietary CSO80 could increase vacuolar fat drops and cause liver damage. The expression levels of peroxisome proliferators-activated receptor alpha and its downstream lipolysis related genes were markedly up-regulated with the increasing of replacement levels of CSO, opposite results were recorded in sterol regulatory element-binding protein-1c and lipogenesis related genes. The malondialdehyde content in liver was decreased with the increasing replacement levels of CSO, whereas the antioxidant parameters were significantly higher in CSO60 group compared to FO group. Phosphatidylinositol-3 kinase and protein kinase B expression levels were significantly up-regulated by dietary CSO80, triggering inflammation by activating nuclear factor kappa b. Dietary CSO60 dramatically promote target of rapamycin expression level. With the increasing replacement levels of FO by CSO, the expression level of ribosomal protein S6 kinase 1 was significantly increased, whereas opposite result was found for the eukaryotic translation initiation factor 4E binding protein 2. Collectively, based on weight gain, double broken line model analysis showed that a maximum growth occurred at 59.13% replacement of dietary FO by CSO. These findings demonstrate that dietary CSO60 can improve growth and antioxidant capacity. However, dietary CSO80 can result in lipid deposition, liver injury and inflammation, hence, suppress growth performance.

Quercetin, Engelitin and Caffeic Acid of Smilax china L. Polyphenols, Stimulate 3T3-L1 Adipocytes to Brown-like Adipocytes Via β3-AR/AMPK Signaling Pathway.

The aim of the present study was to investigate the browning effects mechanism of Smilax china L. polyphenols (SCLP) and its monomer. In this study, polyphenols (SCLP, engeletin, quercetin and caffeic acid) markedly suppressed lipid accumulation. Polyphenols significantly up-graded the expression of protein kinase A (PKA), adipose triglyceride lipase (ATGL), peroxisome proliferators-activated receptors alpha (PPARα), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) to promote lipolysis and β-oxidation. Moreover, polyphenols greatly enhanced mitochondrial biogenesis in adipocytes, as demonstrated by the expression of Nrf1 and Tfam were up-regulated. Furthermore, polyphenols treatment greatly up-regulated the browning program in adipocytes by increased brown-specific genes and proteins uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and PR domain containing 16 (PRDM16), as well as beige-specific genes (Tmem26, Tbx1, CD137, Cited1), especially engeletin. Further research found that the brown-specific markers were decreased by antagonist treatment of AMPK or β3-AR, but polyphenols treatment reversed the effect of antagonists and improved the expression of UCP-1, PRDM16 and PGC-1α. In conclusion, these results indicated that polyphenols stimulate browning in adipocytes via activation of the β3-AR/AMPK signaling pathway, and SCLP and its monomer may be worth investigating to prevent obesity.

Luteolin Pretreatment Attenuates Hepatic Ischemia-Reperfusion Injury in Mice by Inhibiting Inflammation, Autophagy, and Apoptosis via the ERK/PPARα Pathway.

Hepatic ischemia-reperfusion (IR) injury is a clinically significant process that frequently occurs in liver transplantation, partial hepatectomy, and hemorrhagic shock. The aim of this study was to explore the effectiveness of luteolin in hepatic IR injury and the underlying mechanism. BALB/c mice were randomly divided into six groups, including normal controls (NC), luteolin (50 mg/kg), sham procedure, IR+25 mg/kg luteolin, and IR+50 mg/kg luteolin group. Serum and tissue samples were collected at 6 and 24 h after reperfusion to assay liver enzymes, inflammatory factors, expression of proteins associated with apoptosis and autophagy, and factors associated with the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor alpha (ERK/PPARα) pathway. Luteolin preconditioning decreased hepatocyte injury caused by ischemia-reperfusion, downregulated inflammatory factors, and inhibited apoptosis and autophagy. Luteolin also inhibited ERK phosphorylation and activated PPARα.

Dietary Arachidonic Acid (20:4n-6) Levels and Its Effect on Growth Performance, Fatty Acid Profile, Gene Expression for Lipid Metabolism, and Health Status of Juvenile California Yellowtail (Seriola dorsalis)

Arachidonic acid (ARA, 20:4n-6) fed to Seriola dorsalis juveniles at different levels was evaluated. After a seven-week feeding trial, growth performance, hepatopancreas and muscle fatty acid (FA) composition, expression of lipid-relevant genes, and blood parameters were evaluated. Four isoproteic and isolipidic experimental diets were formulated to contain 44% crude protein and 11% lipids with graded inclusion levels of ARA, 0% (Control), 0.4, 0.9, and 1.4% of the total diet. S. dorsalis juveniles (14.54 ± 0.18 g) were randomly divided into twelve tanks with fifteen animals each. The animals were hand fed three times per day to apparent satiation. Dietary treatments did not significantly affect the growth performance, SGR, FCR, and feed intake of fish. Different levels of ARA in the experimental diets directly influenced liver and muscle FA profiles, with significant changes in ARA and EPA deposition between Control treatment and 1.4%, in both tissues. The expression of arachidonate 5-lipoxygenase (alox5), acyl-CoA dehydrogenase very long chain (acadvl), carnitine O-palmitoyltransferase 1(cpt1a) was significantly affected by dietary treatments, with an expression increasing accordingly to the increasing ARA levels. In contrast, a reduction of fatty acid synthase (fas) and proliferator-activated receptor alpha (ppara) expression was significantly reduced as ARA increased in the diet. In addition, a significant reduction in blood cortisol and glucose was found at a 0.9% ARA level compared to the other treatments. Based on the performance, cortisol levels, the gene expression for eicosanoids synthesis, and lipid metabolic pathways, the present study suggests a maximum ARA inclusion of 0.9% in diets for California yellowtail juveniles, S. dorsalis.

Lipid metabolic disorders and physiological stress caused by a high-fat diet have lipid source-dependent effects in juvenile black seabream Acanthopagrus schlegelii.

This study was conducted to evaluate the effects of different dietary lipid sources on growth performance, lipid metabolism, and physiological stress responses including oxidative stress (OS) and endoplasmic reticulum stress (ERS) of juvenile Acanthopagrus schlegelii (initial weight 0.88 ± 0.01g) fed a high-fat diet (HFD). Four isonitrogenous and isolipidic experimental diets containing different lipid sources were formulated: fish oil (FO), palm oil (PO), linseed oil (LO), and soybean oil (SO), respectively. Results indicated that fish fed HFD supplemented with FO significantly improved growth than SO treatment. The high concentrations of aspartate aminotransferase and alanine transaminase were found in HFD supplemented with SO. Fish fed dietary LO supplementation showed significantly lower serum cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein contents than those in SO group. Likewise, hepatic paraffin section analysis indicated that HFD with PO or SO supplementation increased fat drop. The expression levels of peroxisome proliferators-activated receptor alpha (pparα) and silent regulator 1 (sirt1) were significantly elevated by HFD with FO or LO supplementation. Additionally, the key marker of OS malonaldehyde was significantly increased in FO and SO groups. ERS-related genes were activated in dietary PO or SO supplementation and, hence, triggering inflammation and apoptosis by promoting the expression levels of nuclear factor kappa B (nf-κb) and c-Jun N-terminal kinase (jnk). Overall, the present study reveals that lipid metabolic disorders and physiological stress caused by a HFD have significant lipid source-dependent effects, which have important guiding significance for the use of HFD in marine fish.

An fgf21-like gene from swamp eel (Monopterus albus): Recombinant expression and its potential roles in glucose and lipid homeostasis

Fibroblast growth factor 21 (FGF21) plays important roles in the regulation of glucose and lipid metabolism and energy balance in mammals. In this study, the full-length cDNA of swamp eel fgf21 was cloned. Sequence analysis showed that swamp eel FGF21 displayed high similarity with FGF21 of other vertebrates. Subsequently, a prokaryotic expression vector for swamp eel fgf21 was constructed, and recombinant FGF21 (rFGF21) was successfully induced and purified. To investigate the potential roles of swamp eel FGF21 in glucose and lipid metabolism, we examined the effects of rFGF21 on regulation of glucose and lipid homeostasis in type 1 diabetes mellitus (T1DM) mice as well as swamp eels under glucose stress. In T1DM mice, the levels of blood glucose, serum triglyceride (TG), liver TG, serum total cholesterol (TC), and liver TC were significantly downregulated after repeated daily injection of rFGF21 for 15 days. In addition, liver pathological section analysis indicated that rFGF21 alleviated the degree of damage to liver cells in T1DM mice. Furthermore, rFGF21 significantly upregulated the mRNA expression levels of peroxisome proliferators-activated receptor alpha (Pparα), β-Klotho, fibroblast growth factor receptor 1 (Fgfr1), phosphoenolpyruvate carboxykinase (Pepck), glucose transporter 1 (Glut1), and glucose transporter 4 (Glut4) in T1DM mouse livers. Moreover, in swamp eels, rFGF21 significantly decreased blood glucose and liver TC levels under glucose stress and upregulated the mRNA expression levels of fgf21, pparα, β-klotho, and fgfr1 in liver tissue. These results suggested that FGF21 plays important roles in the regulation of glucose and lipid homeostasis in swamp eel.

Real ambient particulate matter-induced lipid metabolism disorder: Roles of peroxisome proliferators-activated receptor alpha

A growing body of evidence associated particulate matter (PM) exposure with lipid metabolism disorders, yet, the underlying mechanism remains to be elucidated. Among the major lipid metabolism modulators, peroxisome proliferator-activated receptor (PPAR) alpha plays an important role. In the current study, an individually ventilated cage (IVC) system was used to expose C57/B6 mice to real-ambient PM for six weeks, with or without co-treatment of PPAR alpha agonist WY14,643. The general parameters, liver and adipose tissue pathology, serum lipids, metal deposition and lipid profile of liver were assessed. The results indicated that six weeks of real-ambient PM exposure induced dyslipidemia, including increased serum triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C) level, along with steatosis in liver, increased size of adipocytes in white adipose tissue (WAT) and whitening of brown adipose tissue (BAT). ICP-MS results indicated increased Cr and As deposition in liver. Lipidomics analysis revealed that glycerophospholipids and cytochrome P450 pathway were most significantly affected by PM exposure. Several lipid metabolism-related genes, including CYP4A14 in liver and UCP1 in BAT were downregulated following PM exposure. WY14,643 treatment alleviated PM-induced dyslipidemia, liver steatosis and whitening of BAT, while enhancing CD36, SLC27A1, CYP4A14 and UCP1 expression. In conclusion, PPAR alpha pathway participates in PM-induced lipid metabolism disorder, PPAR alpha agonist WY14,643 treatment exerted protective effects on PM-induced dyslipidemia, liver steatosis and whitening of BAT, but not on increased adipocyte size of WAT.

Mitochondria damage in ambient particulate matter induced cardiotoxicity: Roles of PPAR alpha/PGC-1 alpha signaling

Particulate matter (PM) had been associated with cardiotoxicity, while the mechanism of toxicity has yet to be elucidated, with mitochondria dysfunction as a potential candidate. To investigate the potential cardiotoxic effects of ambient PM exposure and assess the damage to cardiac mitochondria, C57/B6 mice were exposed to filtered air or real ambient PM for three or six weeks. Furthermore, to reveal the role of peroxisome proliferators-activated receptor alpha (PPAR alpha) in PM exposure induced cardiotoxicity/mitochondria damage, animals were also co-treated with PPAR alpha agonist WY 14,643 or PPAR alpha antagonist GW 6471. Cardiotoxicity was assessed with echocardiography and histopathology, while mitochondria damage was evaluated with mitochondria membrane potential measurement and transmission electron microscopy. Potential impacts of PM exposure to PPAR alpha signaling were detected with co-immunoprecipitation and western blotting. The results indicated that exposure to ambient PM exposure induced cardiotoxicity in C57/B6 mice, including altered cardiac functional parameters and morphology. Cardiac mitochondria damage is detected, in the form of compromised mitochondria membrane potential and morphology. Molecular investigations revealed disruption of PPAR alpha interaction with peroxisome proliferator-activated receptor gamma coactivator-1A (PGC-1a) as well as altered expression levels of PPAR alpha downstream genes. Co-treatment with WY 14,643 alleviated the observed toxicities, while co-treatment with GW 6471 had mixed results, exaggerating most cardiotoxicity and mitochondrial damage endpoints but alleviating some cardiac functional parameters. Interestingly, WY 14,643 and GW 6471 co-treatment seemed to exhibit similar regulative effects towards PPAR alpha signaling in animals exposed to PM. In conclusion, ambient PM exposure indeed induced cardiotoxicity in C57/B6 mice, in which cardiac mitochondria damage and disrupted PPAR alpha signaling are contributors.

Carnitine palmitoyltransferase 1 (CPT1) alleviates oxidative stress and apoptosis of hippocampal neuron in response to beta-Amyloid peptide fragment Aβ25-35

ABSTRACT CPT1C, which is expressed in hippocampus, influences ceramide level, endogenous cannabinoid and oxidation process, as well as plays an important role in various brain functions such as learning. This study aimed to investigate the role of CPT1C in Alzheimer’s disease (AD) and its underlying mechanism. We established a model of Alzheimer’s disease in vitro by exposing primary hippocampal neurons to beta-Amyloid peptide fragment 25–35 (Aβ25-35). The cell viability, lactate dehydrogenase (LDH) level, expressions of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected using Cell Counting Kit-8 (CCK-8), LDH assay, ROS kits, malondialdehyde (MDA) kits and SOD kits, respectively. Moreover, the expression of oxidative stress-related proteins as well as the expressions of amyloid precursor protein (App), p-Tau andβ-site APP-cleaving enzyme1 (Bace-1) were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot. Tunel and western blot were adopted to detect apoptosis as well as its related proteins. After the treatment of peroxisome proliferators-activated receptor alpha (PPARα), CPT1C expression was detected with the application of RT-qPCR and western blot. CPT1C expression was reduced in Aβ25-35-induced HT22 cells. Overexpression of CPT1C relieved cell viability and toxic injury as well as attenuated oxidative stress, apoptosis and expression levels of AD marker proteins. Moreover, higher doses of PPARα agonist activate the expression of CPT1C in Aβ25-35-induced HT22 cells. In conclusion, CPT1C alleviates Aβ25-35-induced oxidative stress, apoptosis and deposition of AD marker proteins in hippocampal neurons, suggesting that CPT1C has favorable effects on alleviating AD and participates in PPARα activation.

Mitochondrial Metabolism, Dysfunctions in Senescence Cell and the Possible Interventions through Herbal Medicines

The mitochondria are the cell`s powerhouse. They are considered ubiquitous organelles of all eukaryotic cells, being responsible for the cell’s life and death cycle. Through stimuli in the environment in which they live, mitochondria can modulate their own biogenesis as well as signal retrograde to the nucleus to modify the structure of their proteins. Since the mitochondrial genome contains only 37 genes, much of the encoding of its proteins depends on the nuclear genome. Thus, the communication between mitochondria and the nucleus seems to be a target of science in understanding the pathologies associated with this organelle. Some medicinal herbs have been shown to influence mitochondrial biogenesis, such as Gynostemma pentaphyllun (GP) and berberine, which increase the phosphorylation of proteins AMPactivated protein kinase (AMPK). Just as GP and berberine phosphorylate AMPK in signaling for mitochondrial biogenesis, the sesquiterpene beta-caryophyllene (BCP) demonstrated positive results in reorganizing mitochondrial transcription factors, being an agonist of the peroxisome proliferatoractivated alpha receptor (PPAR-α). Another plant derivative, the non-psychoactive cannabinoid known as cannabidiol (CBD), has been showing control in the metabolism of calcium in the mitochondrial matrix. In this review, we seek to get a closer look at the biochemical mechanisms of action of some of these plants, as well as their synergies in the results of different treatments. In the view of oriental medicines, the use of associated medicinal herbs has always been part of their treatment protocols. However, the effectiveness of these treatments in relation to plant synergy can be observed in future clinical trials for better understanding.

Pemafibrate protects the rupture of experimental aortic aneurysm in mice through anti-oxidative stress with induced catalase

Abstract Background Abdominal aortic aneurysm (AAA) is a life-threatening disease, while effective and preventive medical treatments remain unestablished. Purpose The aim of this study was to evaluate the effect of selective peroxi- some proliferator-activated receptor alpha (PPARα) modulator pemafibrate on AAA formation in mice. Methods AAA was induced by subcutaneous infusion of angiotensin II (AngII) in apolipoprotein E-deficient mice for 4 weeks. Treatment by pemafibrate or vehicle was started one week before AngII infusion. Oxidative stress was evaluated by dihydroethidium (DHE) staining. Results Prognosis after AngII infusion in pemafibrate-treated mice was significantly better than that in vehicle-treated mice (log-rang test, p=0.035) by reducing the occurrence of fatal AAA rupture. Meanwhile pemafibrate did not significantly reduce maximal diameter of the aorta. Histological findings demonstrated that the expression of collagen in adventitia in pemafibrate-treated mice was significantly greater than that in vehicle-treated mice (p&amp;lt;0.05). Oxidative stress in aorta of pemafibrate-treated mice was significantly reduced comparing to vehicle-treated mice, accompanying by the reduction of mRNA expression of matrix metalloproteinase 2, tumor necrosis factor-α, and interleukin-6 (all p&amp;lt;0.05). Catalase expression in abdominal aortic tissue was increased 1.5-fold in mice treated with pemafibrate than in mice treated with vehicle (p=0.032). In human vascular smooth muscle cells (hVSMC), pemafibrate attenuated AngII-induced oxidative stress (p&amp;lt;0.001), which was canceled by administrating small interfering RNA (siRNA) of PPARα (p&amp;lt;0.001). Furthermore, in hVSMC, pemafibrate increased catalase expression significantly (p&amp;lt;0.001), while this increase was significantly suppressed by knockdown of PPAR-α with siRNA. (p&amp;lt;0.001). Conclusion Pemafibrate reduced the rupture of AAA in this murine model, which is associated with anti-oxidative stress via catalase induction. Funding Acknowledgement Type of funding source: None

Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21.

Fibroblast growth factor 21 (FGF21) is a recently discovered hepatokine that regulates lipid and glucose metabolism and is upregulated in response to numerous physiological and pathological stimuli. Herein, we demonstrate that both physical and chemical hypoxia increase the systemic and hepatic expression of FGF21 in mice; by contrast, hypoxia induces a reduction of FGF21 expression in hepatocytes, indicating that hypoxia-induced FGF21 expression is differentially regulated in intact animals and in hepatocytes. Furthermore, we demonstrate that hypoxia treatment increases hormone-sensitive lipase-mediated adipose tissue lipolysis in mice, which is reduced in Fgf21 knockout mice, thereby implying that FGF21 plays a critical role in hypoxia-related adipose lipolysis. Adipose tissue lipolysis causes an increase in the amount of circulating free fatty acids, which leads to the activation of peroxisome proliferators-activated receptor alpha and an increased expression of FGF21 in hepatocytes. We further show that hypoxia-induced elevation of reactive oxygen species, but not the hypoxia-inducible factor, is responsible for the lipolysis and FGF21 expression. In conclusion, our data clearly demonstrate that FGF21 plays a critical role in hypoxia-induced adipose lipolysis, which induces hepatic expression of FGF21. Clarification of hypoxia-regulated FGF21 regulation will enhance our understanding of the pathophysiology of hypoxia-related diseases, such as sleep disorders and metabolic diseases.

Effects of dietary n-3 highly unsaturated fatty acids levels on growth, lipid metabolism and innate immunity in juvenile golden pompano (Trachinotus ovatus)

To investigate the effects of dietary n-3 highly unsaturated fatty acids (HUFA) levels on growth, lipid metabolism and innate immunity in juvenile golden pompano Trachinotus ovatus, a marine carnivorous teleost, a total of 450 fish (average body weight: 14.84 g) were randomly distributed into 18 cages at sea, each dietary group with three cages and respectively fed six diets (D1-D6) with 2.30% (D1), 0.64% (D2), 1.00% (D3), 1.24% (D4), 1.73% (D5), or 2.10% (D6) n-3 HUFA. Here, D1 with fish oil as lipid source was set as control, while D2-D6 used a mixed vegetable oil as lipid source and supplemented with docosahexaenoic acid- (DHA) and eicosapentaenoic acid- (EPA) enriched oils to adjust the n-3 HUFA levels. After 8 weeks feeding, the daily growth coefficient (DGC), specific growth rate (SGR) and feed efficiency ratio (FER) showed no significant difference among the six dietary groups (P > 0.05). The levels of EPA and DHA in serum and liver increased with the dietary n-3 HUFA levels. The activity of total superoxide disumutase (T-SOD) in serum of fish fed D4 and D5 were significantly higher than that of the other groups, whereas the opposite was true for serum IL-1β and IL-6 levels as well as liver malondialdehyde (MDA) content. The mRNA levels of genes related to hepatic lipid metabolism including sterol regulatory element-binding protein-1 (srebp-1), fatty acid binding protein 1 (fabp1), peroxisome proliferators-activated receptor alpha (pparα), elongase of very long-chain fatty acids 5 (elovl5) and fatty acyl desaturase 2 (fads2) were down-regulated in fish fed the diets with high n-3 HUFA levels, while those of apolipoprotein b 100 (aprob 100) and carnitine palmitoyl transferase 1 (cpt1) increased significantly as increasing n-3 HUFA levels up to 1.73% (D2-D5), but decreased in the 2.10% n-3 HUFA group (D6). In addition, the expression levels of genes related to innate immunity including interleukin-10 (il-10) and transforming growth factor β1 (tgf-β1) increased significantly when dietary n-3 HUFA increased from 0.64% to 1.73%, whereas the opposite was true for the expression levels of nuclear factor kappa-B (nf-κb), interleukin-1β (il-1β), interleukin-6 (il-6) and interleukin-8 (il-8). Overall, the results indicated that dietary n-3 HUFA at 1.24–1.73% (D4-D5) can effectively improve fatty acid profiles, lipid metabolism, antioxidant capacity and immune response of golden pompano.

Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway.

PurposeNonalcoholic fatty liver disease (NAFLD) has become a predictor of death in many diseases. This study was carried out to investigate the therapeutic effect of Radix Polygoni Multiflori Preparata (RPMP) and its main component emodin on egg yolk powder-induced NAFLD in zebrafish. Further investigation was performed to explore whether emodin was the main component of RPMP for the treatment of NAFLD as well as the underlying therapeutic mechanism of RPMP and emodin.MethodsZebrafish were divided into control group, egg yolk powder group, RPMP group and emodin group. The obesity of zebrafish was evaluated by body weight, body length and BMI. The content of lipid was detected by triglyceride (TG), total cholesterol (TC) reagent kit and the fatty acid was detected by nonesterified free fatty acids (NEFA) reagent kit. HE staining was used to detect the histological structure of liver. Whole-mount Oil red O staining and Frozen oil red O staining were carried out to investigate the lipid accumulation in liver. KEGG and STRING databases were performed to analyze the potential role of AMPK between insulin resistance (IR) and fatty acid oxidation. Western blot and RT-qPCR were carried out for mechanism research.ResultsRPMP and emodin significantly reduced zebrafish weight, body length and BMI. Both RPMP and emodin treatment could reduce the lipid deposition in zebrafish liver. RPMP significantly reduced the content of TG. However, emodin significantly reduced the contents of TG, TC and NEFA in zebrafish with NAFLD. The protein interaction network indicated that AMPK participated in both IR and fatty acid oxidation. Further investigation indicated that RPMP and emodin reduced hepatic lipogenesis via up-regulating the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT2), amp-activated protein kinase alpha (AMPKα), proliferator-activated receptor alpha (PPARα), carnitine palmitoyl transferase 1a (CPT-1a) and acyl-coenzyme A oxidase 1 (ACOX1).ConclusionThese findings suggest that emodin is the main component of RPMP for the treatment of NAFLD, which is closely related to the regulation of AMPK signaling pathway which increases IR and fatty acid oxidation.

Quantitative proteomics analysis of Fructus Psoraleae-induced hepatotoxicity in rats

Fructus Psoraleae, which is commonly consumed for the treatment of osteoporosis, bone fracture, and leucoderma, induces liver injury. This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae (EEFP)-induced liver injury in rats. EEFP (1.35, 1.80, and 2.25 g·kg-1) was administrated to Sprague Dawley (SD) rats for 30 d. We measured liver chemistries, histopathology, and quantitative isobaric tags for relative and absolute quantitation (iTRAQ)-based protein profiling. EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion, bile flow rate, and liver histopathology. iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats. Among these proteins, 81 were upregulated and 32 were downregulated in the treatment group. KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450, glutathione metabolism, glycerolipid metabolism, and bile secretion were enriched with differentially expressed proteins. The expression of key proteins related to the farnesoid X receptor (FXR), i.e., the peroxisome proliferators-activated receptor alpha (PPAR-α), were downregulated, and multidrug resistance-associated protein 3 (MRP3) was upregulated in the EEFP-treated rats. Our results provide evidence that EEFP may induce hepatotoxicity through various pathways. Furthermore, our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.

Anti-obesity effects of individual or combination treatment with Spirulina platensis and green coffee bean aqueous extracts in high-fat diet-induced obese rats

Background: Obesity is associated with serious health risks, including premature mortality. This study investigated the anti-obesity effects of individual or combination treatment with Spirulina platensis and green coffee bean aqueous extracts in high-fat diet-induced (HFD) obese rats.Methods: Rats were fed on HFD to induce obesity. Corn oil in the HFD accounted for 50.98% of the calories. Fifty rats were divided into five groups (10 rats/group): control, HFD, HFD-Spirulina, HFD-coffee, HFD-Spirulina and coffee cotreatment groups. The serum levels of lipid, leptin, and insulin, as well as the hepatic mRNA levels of fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and peroxisome proliferator-activated alpha receptor (PPARα) were estimated.Results: The Spirulina and/or green coffee bean aqueous extracts decreased the final bodyweight and liver weight, and the serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. The extracts decreased the serum levels of total cholesterol, triacylglycerol, low-density lipoprotein-cholesterol, leptin, and glucose, and enhanced the serum insulin level. Furthermore, the extracts enhanced the PGC-1α and PPARα mRNA levels and decreased the FAS mRNA levels.Conclusion: The individual or combination treatment with Spirulina platensis and green coffee bean extracts decreased obesity-induced hyperlipidemia and they can be potentially used to treat obesity. Abbreviations: ACC: Acetyl Co-A carboxylase; AF: Activity factor; ALP: Alkaline phosphatase; ALT: Alanine amino transferase; AMP: Adenosine monophosphate; AMPK: AMP activated protein kinase; AST: Aspartate amino transferase; BMI: Body mass index; cAMP: Cyclic adenosine monophosphate; CBE: Coffee bean extract; CVD: Cardiovascular disorder; DRD4: Dopamine receptor D4; FAS: Fatty acid synthase; FFA: Free fatty acid; FTO: Fat mass and obesity gene; GOD: Glucose oxidase; G-6-P: Glucose-6-phosphatase; HDL-C: High-density lipoprotein-cholesterol; HFD: High-fat diet; HMGRCR: 3-hydroxy-3-methylglutaryl CoA reductase; LDL-C: Low-density lipoprotein-cholesterol; LXR α: Liver X receptor α; MC4R: Melanocortin 4 receptor gene’; NO: Nitric oxide; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha; PPARα: Peroxisome proliferator-activated alpha; PPARγ: Peroxisome proliferator-activated receptor γ; REE: Resting energy expenditure; ROS: Reactive oxygen species; TC: Total cholesterol; T2DM: Type 2 diabetes; TG: Triacyl glycerol; TP: Total protein; VLDL: Very low-density lipoprotein; WLS: Weight loss surgery

Effects of supplemental dietary l-carnitine and bile acids on growth performance, antioxidant and immune ability, histopathological changes and inflammatory response in juvenile black seabream (Acanthopagrus schlegelii) fed high-fat diet

Numerous studies have demonstrated that l-carnitine (LC) and bile acids (BA) could improve growth performance, reduce fat deposition and affect the inflammatory response in fish. Hence, the main aim of the present study was to find out whether dietary LC or BA supplementation have effects on antioxidant and immune parameters, histopathological changes and inflammatory response in juvenile black seabream (Acanthopagrus schlegelii) fed high-fat diet (HFD). An 8-week feeding trial was conducted in juvenile black seabream of initial weight 2.17 ± 0.00 g. Four isonitrogenous diets (42%) were formulated, Diet1: low fat diet (11%)，Diet2: high-fat diet (17%), Diet3: high-fat diet with LC (300 mg/kg dry diet) and Diet4: high-fat diet with BA (200 mg/kg dry diet). There were no significant differences on growth performance and feed utilization among treatments. Fish fed Diet2, Diet3 and Diet4 had higher intraperitoneal fat ratio (IPF) and lipid content in muscle than Diet1 treatment. Tissue fatty acid profiles reflected the diets. The values of alkaline phosphatase (AKP) and malondialdehyde (MDA) in fish serum fed Diet2, Diet3 and Diet4 were significantly higher than Diet1 treatment. The highest lysozyme (LZM) activities in serum and liver were recorded in fish fed Diet3 and Diet4, respectively. Besides, fish fed with Diet3 and Diet4 obtained significantly higher catalase (CAT) activity when compared to Diet1 and Diet2 groups. With regards to hematological characteristics, the values of triglyceride (TG), cholesterol (CHOL) and high-density lipoprotein cholesterol (HDL-C) in fish fed diet1 were significantly higher than other treatments. However, fish fed with Diet2 showed the highest content of low-density lipoprotein cholesterol (LDL-C). The results of paraffin section of liver (400×) revealed that compared to the negative control diet (Diet 2), the shapes of some cells are regular and parts of the cell structure remained normal, some of the nucleus with nucleolus is spherical, the vacuolar fat drops are smaller and less in Diet 3 treatment, indicating that the dietary LC supplementation could be able to prevent or ameliorate the histopathological alterations induced in liver. Moreover, the hepatic triglyceride content in fish fed with Diet 3 was significantly lower than Diet2 group. The expression of pro-inflammatory cytokine including tumor necrosis factor alpha (tnfα) and interleukin 1β (il-1β) were down-regulated by LC and BA, whereas the anti-inflammatory cytokine transforming growth factor β1 (tgfβ-1) did not show any statistic differences among treatments. Besides, the hepatic fatty acid β-oxidation related genes peroxisome proliferators-activated receptor alpha (pparɑ) and carnitine palmitoyl transferase 1A (cpt1a) in fish fed with Diet 3 and Diet 4 are significantly higher than Diet 2 treatment. Overall, this study indicated that dietary LC and BA could significantly enhance antioxidant, fatty acids β-oxidation and immune ability, reduce inflammatory responses, it also had positive impacts on histopathological changes but could not improve growth performance and feed utilization of black seabream fed HFD.