Liver Lipid Content Research Articles

PREMATURE MENOPAUSE AND OBESITY DUE TO OOCYTE LOSS IN FEMALE MICE CHRONICALLY EXPOSED TO LOW DOSE-RATE γ-RAYS.

In previous reports, the authors showed a significant overall increase in neoplasms originating from the ovaries (2007) and increased body weights (2007, 2010) in female B6C3F1 mice chronically exposed to low dose-rate γ-rays at 20mGy/day (total doses=8 (2007) or 6Gy (2010)), as well as significant increases in serum leptin, total cholesterol, adipose tissue deposits and liver lipid content (2010). The present study chronicles the progression of ovarian failure in relation to obesity and dyslipidemia in female B6C3F1 mice chronically exposed to low dose-rate of γ-rays from 9 to 43weeks of age (total dose=4.8Gy). We monitored changes in body weights, estrus cycles, ovarian follicle counts, serum cholesterol and serum leptin. The number of mice with irregular estrus cycles and increased body weights (with increased fat deposits) significantly increased from 30-36weeks of age. Depletion of oocytes in ovaries from irradiated mice at 30weeks of age (accumulated dose=3Gy) was also observed. Findings suggest that obesity in female B6C3F1 mice continuously irradiated with low dose-rate of γ-rays at 20mGy/day is a consequence of premature menopause due to radiation-induced oocyte depletion.

Fuzi-Lizhong Decoction Alleviates Nonalcoholic Fatty Liver Disease by Blocking TLR4/MyD88/TRAF6 Signaling.

Background Fuzi-Lizhong decoction (FLD) derives from the ancient Chinese Pharmacopoeia and has been clinically used for years. The present study aimed to investigate the activities and underlying mechanisms of FLD against nonalcoholic fatty liver disease (NAFLD). Methods In vivo studies were conducted by inducing NAFLD in rats with a high-fat diet, and in vitro studies were performed on HL-7702 cells treated with oleic and linoleic acids. Total cholesterol (TC), triglyceride (TG), and blood glucose (Glu) levels were detected using an automatic biochemical analyzer. The expression of IL-2, IL-6, and TNF-α in sera and cell culture supernatants was measured by ELISA. The mRNA and protein levels of TLR4, MyD88, and TRAF6 were measured in liver tissue and HL-7702 cells using reverse transcription-quantitative polymerase chain reaction and western blot. Results FLD significantly reduced the TC, TG, Glu, FFA, IL-2, IL-6, and TNF-α levels in NAFLD rats and HL-7702 cells. Analysis of liver lipid content by Oil Red O staining revealed a significant increase in hepatic lipid accumulation in rats with NAFLD, but this lipid accumulation was reversed by FLD treatment. In addition, the mRNA expression levels of TLR4, MyD88, TRAF6, and NF-κB p65 as well as the protein levels of TLR4, MyD88, TRAF6, and NF-κB p65 were decreased after FLD treatment. FLD significantly reduced inflammation and improved collagen accumulation in vivo and in vitro by inhibiting the activation of the TLR4/MyD88/TRAF6 signaling pathway. Conclusions FLD exerted potent protective effects against NAFLD via TLR4/MyD88/TRAF6 signaling. These findings provide novel insights into the mechanisms whereby this compound acts as an anti-inflammatory agent and highlight the potential application of FLD in the treatment of acute liver failure (ALF).

Insights into the correlations between prebiotics and carbohydrate metabolism in fish: Administration of xylooligosaccharides in Megalobrama amblycephala offered a carbohydrate-enriched diet

Dietary supplementation of xylooligosaccharides (XOS) represents a potential means to improve the carbohydrate metabolic disorders in type 2 diabetes. However, whether XOS could improve the carbohydrates utilization and metabolism of fish is still unknown. This study investigated the effects of XOS on the growth performances and glycolipid metabolism of blunt snout bream (Megalobrama amblycephala) fed a high carbohydrate (HC) diet. Fish (44.69 ± 0.11 g) were fed a control diet (29% carbohydrate), a HC diet (41% carbohydrate), and the HC diet supplemented with 0.5%, 1.0%, 1.5% and 2.0% XOS respectively for 12 weeks. Compared with the control group, the HC group obtained significantly high values of final body weight, weight gain rate, intraperitoneal fat ratio, whole-body lipid content, liver and intraperitoneal fat glycogen contents, tissue lipid contents, glycated serum protein (GSP) levels, and the transcriptions of sodium glucose cotransporter 1, glucose transporter 2 (glut2), glucokinase (gk), pyruvate kinase (pk), glycogen synthase (gs), fatty acid synthetase (fas) and acetyl-CoA carboxylase α (accα), and the decreased values of feed conversion ratio and hepatic transcriptions of carnitine palmitoyl transferase 1 (cpt-1) and acyl-CoA oxidase (aco). Meanwhile, the supplementation of 1.0% XOS significantly increased the nitrogen retention efficiency, liver glycogen contents, and the transcriptions of glut2, gk, pk, glucose-6-phosphate, cpt-1 and aco compared with the HC group, while the opposite was true for liver and muscle lipid contents, plasma TG, total cholesterol and GSP levels, and the transcriptions of fas and accα. Collectively, dietary supplementation of 1.0% XOS could improve the growth performance and glycolipid metabolism of blunt snout bream fed a high-carbohydrate diet by up-regulating glucose transport, glycolysis, glycogenesis, the pentose phosphate pathway and fatty acids β-oxidation, but down-regulating gluconeogenesis and fatty acid biosynthesis

Regular exercise combined with ferulic acid exhibits antiobesity effect and regulates metabolic profiles in high-fat diet-induced mice.

Exercise (Ex) has been recognized as an effective way of obesity prevention, but it shows a dual effect on the body's antioxidant system. Ferulic acid (FA) is a kind of phenolic acid with well-known antioxidant capacity and numerous health benefits. Therefore, the aim of the study was to compare the antiobesity effect of Ex, FA, and Ex combined with FA (Ex-FA) in vivo and to illustrate the potential mechanisms. Mice were fed a high-fat diet (HFD) with or without administration of Ex, FA, and Ex-FA for 13 weeks. The body weight, antioxidant ability, Ex performance, and lipid profiles in the serum, liver, and skeletal muscle were compared among the groups, and serum metabolomics analysis was conducted. The results showed that Ex, FA, and Ex-FA exhibited a similar effect on body weight management. Ex had a more beneficial function by alleviating HFD-induced dyslipidemia than FA, while FA exerted a more efficient effect in mitigating lipid deposition in the liver and skeletal muscle. Ex-FA showed comprehensive effects in the regulation of the lipid contents in serum, liver, and skeletal muscle, and provoked enhancement effects on antioxidant ability and Ex capacity. Mice administered with Ex, FA, and Ex-FA showed different metabolic profiles, which might be achieved through different metabolic pathways. The findings of this research implied that Ex coupled with FA could become an effective and safe remedy for the management of dietary-induced obesity.

Tamoxifen induced hepatic steatosis in high-fat feeding rats through SIRT1-Foxo1 suppression and LXR-SREBP1c activation.

Clinically, long-term use of tamoxifen (TAM) would lead to fatty liver disease in breast cancer patients, especially obese women. However, the exact mechanism of TAM-induced hepatic steatosis is still unclear. Meanwhile, there is no drug to prevent and treat it. In view of silent information regulator 1 (SIRT1) playing a key role in hepatic lipid metabolism regulation, this study was conducted to investigate whether SIRT1 is a potential therapeutic target for TAM-induced hepatic steatosis. In this study, obese female Wistar rats fed with high-fat diet (HFD) for 15weeks were given TAM (4, 8mg/kg, intragastric) for 14days. In vitro, human hepatocarcinoma cell line HepG2 was used to establish a high-fat model with 50μM oleic acid and TAM (10μM) was treated simultaneously for 72h. The results showed that TAM was more likely to upregulate the expression of lipid synthetase that caused the increase of lipid content in HepG2 cells and rat liver. The expression of SIRT1 was downregulated both in vitro and in vivo. SIRT1 agonist SRT1720 (15mg/kg, 30mg/kg, i.p.) could resist TAM-induced hepatic lipid synthetase overexpression to relieve TAM-induced hepatic steatosis. Meanwhile, the upregulation of p-forkhead box O1 and LXRα induced by TAM was reversed by SRT1720. These results indicated that TAM-induced hepatic steatosis was based on SIRT1-p-FoxO/LXRα-sterol regulatory element binding protein 1c pathway under HFD condition. SIRT1 agonist might be a potential therapeutic drug to relieve this side effect. Tamoxifen increased lipid synthesis and regulated lipid transport in HFD rat liver.p-FoxO1/LXRα-SREBP1c signaling was upregulated through the inhibition of SIRT1 in tamoxifen-induced hepatic steatosis under HFD condition.SIRT1 agonist SRT1720 could relieve tamoxifen-induced hepatic steatosis.

Hepatic Transcriptome Analysis Provides New Insight into the Lipid-Reducing Effect of Dietary Taurine in High-Fat Fed Groupers (Epinephelus coioides).

A transcriptome analysis was conducted to provide the first detailed overview of dietary taurine intervention on liver lipid accumulation caused by high–fat in groupers. After an eight-week feeding, the fish fed 15% fat diet (High–fat diet) had higher liver lipid contents vs. fish fed 10% fat diet (Control diet). 15% fat diet with 1% taurine (Taurine diet) improved weight gain and feed utilization, and decreased hepatosomatic index and liver lipid contents vs. the High–fat diet. In the comparison of the Control vs. High–fat groups, a total of 160 differentially expressed genes (DEGs) were identified, of which up- and down-regulated genes were 72 and 88, respectively. There were 49 identified DEGs with 26 and 23 of up- and down-regulated in the comparison to High–fat vs. Taurine. Several key genes, such as cysteine dioxygenase (CDO1), ADP–ribosylation factor 1/2 (ARF1_2), sodium/potassium–transporting ATPase subunit alpha (ATP1A), carnitine/acylcarnitine translocase (CACT), and calcium/calmodulin–dependent protein kinase II (CAMK) were obtained by enrichment for the above DEGs. These genes were enriched in taurine and hypotaurine metabolism, bile secretion, insulin secretion, phospholipase D signaling pathway, and thermogenesis pathways, respectively. The present study will also provide a new insight into the nutritional physiological function of taurine in farmed fish.

Rapamycin did not prevent the excessive exercise-induced hepatic fat accumulation

AimsThe excessive eccentric exercise led to hepatic fat accumulation, which occurred concomitantly with elevation in the mammalian target of the rapamycin complex 1 (mTORC1) and insulin signaling pathways. Since mTORC1 and insulin can inhibit the autophagy pathway and explain the liver lipid content elevation, the main objective of the present investigation was to verify the responses of genes and proteins related to the autophagy and lipogenesis pathways in the hepatic tissue of mice submitted to the excessive downhill running protocol with and without rapamycin administration, a drug able to inhibit the mTORC1 pathway. Main methodsC57BL/6J mice were divided into four experimental groups: Control (CT; sedentary), Excessive exercise in downhill running (EE), Excessive exercise in downhill running with chronic administration of rapamycin (EE/Rapa), and Endurance exercise (END). At the end of the protocols, the blood and liver were collected for serum analysis, histology, immunohistochemistry, hepatic fat content, reverse transcription-quantitative polymerase chain reaction, and immunoblotting. Key findings1) higher levels of glucose, insulin, HOMA-IR, cortisol, ALT, and cholesterol, but lower levels of T4 for the EE/Rapa group; 2) hepatic fat accumulation for the EE and EE/Rapa groups; 3) upregulation of LC3 immunoexpression and downregulation of autophagic flux index for the EE and EE/Rapa groups; 4) reduction of P70S6K phosphorylation and SQSTM1 and increase of FOXO1A phosphorylation for the EE/Rapa group. SignificanceThe excessive exercise in downhill running with or without rapamycin led to increased liver fat content. Although rapamycin was effective in inhibiting mTORC1, the autophagy flux was not upregulated.

Dynamic Transcriptomic Profiling During Liver Development in Schizothorax Prenanti.

Liver is an important organ for glucose and lipid metabolism, immunity, and detoxification in fish. However, the gene regulatory network of postnatal liver development still remains unknown in teleost fish. In this study, we performed transcriptome analysis on the liver of S. prenanti at three stages. A total of 1692 differentially expressed genes (DGEs) were identified across three liver developmental stages. The oil red O staining and PAS staining revealed that the lipid content of liver was increased and the glycogen content of liver was decreased during liver development. The fatty acids biosynthesis related genes were upregulated in adult and young stages compared with juvenile stage, while lipid degradation related genes were downregulated. The genes related to glycolysis, gluconeogenesis and glycogenolysis were upregulated in juvenile or young stages compared with adult stage. Further pathway analysis indicated that the CYP450 pathway, cell cycle and amino acid metabolic pathway were induced in the process of liver maturation. Our study presents the gene expression pattern in different liver development stages of S. prenanti and may guide future studies on metabolism of S. prenanti liver.

The hypolipidemic, anti-inflammatory and antioxidant effect of Kavolì® aqueous extract, a mixture of Brassica oleracea leaves, in a rat model of NAFLD

Herein we characterized the bioactive metabolites of the aqueous extract of Kavolì®, a commercial product composed of a mixture of Brassica oleracea leaves, and assessed its potential ameliorating effects in a rat model of non-alcoholic fatty liver disease (NAFLD). Kavolì® extract showed high levels of bioactive compounds and strong in vitro antioxidant activities. Chlorogenic and neochlorogenic acids were identified as the most representative polyphenols. The administration of brassica extract to steatotic rats significantly ameliorated the levels of blood lipids and transaminases, and lipid content and inflammatory markers in liver. Oxidative stress parameters were significantly improved in both liver and brain of steatotic rats. Moreover, plasma and feces levels of short chain fatty acids (SCFAs) were bring back close to control values by Kavolì® treatment, in spite of high fat diet/streptozotocin (HFD/STZ)-induced alterations. The efficacy of Kavolì® in treating hypercholesterolemia, reducing the level of inflammation and cardiovascular disease biomarkers, steatosis and oxidative stress parameters, as well as the ability in modulating SCFAs levels is probably related to the bioactive compounds of the water extract administered to the rat model of NAFLD. In particular, the ameliorating effects are largely attributable to the high content in polyphenols observed in our study.

Effects of Elephantopus scaber extract on growth, proximate composition, immunity, intestinal microbiota and resistance of the GIFT strain of Nile tilapia Oreochromis niloticus to Streptococcus agalactiae

This study aimed to investigate the effects of Elephantopus scaber extract on the GIFT (genetic improvement of farmed tilapia) strain of Nile tilapia Oreochromis niloticus. A total of 800 tilapia with an initial body weight of 1.34 ± 0.09 g each were randomly divided into five groups. The tilapia in the control group (E0 group) were fed on a basal diet only. Meanwhile, tilapia in the four experimental groups were fed on a basal diet supplemented with 1 g/kg (E1 group), 3 g/kg (E2 group), 5 g/kg (E3 group), and 7 g/kg (E4 group) of E. scaber extract for 10 weeks. Results showed that the survival rate was higher in the experimental groups than in the control group. Compared with the control group, some growth parameters (FW, WGR, SGR, VSI, and HSI) were significantly improved in the E1 group and E2 group. The crude lipid content in the dorsal muscle and liver was lower in the E1 group than in the control group. After E. scaber extract supplementation, activities of immunity-related enzymes (ACP, AKP, T-AOC, SOD, CAT, GSH-Px and LZM) in plasma, liver, spleen and head kidney, and expressions of immunity-related genes (IL-1β, IFN-γ, TNF-α, and CCL-3) in liver, spleen and head kidney showed various degrees of improvement, while MDA content and Hsp70 expression level were decreased. The survival rate of tilapia increased in all the supplementation groups after Streptococcus agalactiae treatment. E. scaber extract addition changed the species composition, abundance, and diversity of intestinal microbiota in tilapia. These results demonstrate that E. scaber extract supplementation in diet can improve the growth, immunity, and disease resistance of GIFT against S. agalactiae. E. scaber extract supplementation can also change intestinal microbiota and reduce crude lipid content in dorsal muscle and liver. The above indicators show that the optimal dose of E. scaber extract for GIFT is 1 g/kg.

1379-P: Combination of FGF21 and ß3-Adrenergic Treatment in Obese Mice

An induction of lipolysis by β3-adrenergic agonist CL316,243 (CL) increases plasma free fatty acid (FFA) level resulting later in ectopic lipid accumulation in liver. The peak of FFA stimulates insulin secretion and causes acute drop of blood glucose (BG) in chow-fed mice. This glucose-lowering effect is attenuated in insulin-resistant dietary obese (DIO) mice. Fibroblast growth factor 21 (FGF21) treatment increases insulin sensitivity while inhibiting lipolysis. Both FGF21 and CL induce uncoupling protein 1 (UCP1) in brown adipose tissue, increasing capacity for combustion of glucose. Thus, the FGF21 treatment has a potential to modulate the glucoregulatory action of CL. Here we aim to characterize the effect of the CL+FGF21 combination and to investigate the role of UCP1 in this effect. DIO C57Bl/6 mice were housed at 30 °C in order to minimize basal adrenergic tone. Animals were treated 2x daily with 65 μg FGF21 or its vehicle for 8 days. This treatment lowered insulin (increased insulin sensitivity) . Subsequently, the mice were injected with 35 μg CL or with saline. CL increased FFA and insulin in control mice, but did not affect BG (probably because of impaired insulin sensitivity) . The day after CL injection, 4-fold rise in ectopic lipid content in liver was observed in comparison to saline-treated group. In FGF21-treated mice, the CL-induced rise of NEFA and insulin was only transient, but sufficient to cause a drop of BG. The hepatic lipid accumulation after CL was completely preveted by FGF21. The same experimental set-up was repeated in DIO UCP1+/+ and -/- mice. Although the BG-lowering effect of the CL+FGF21combination was observed in both genotypes, the effect was significantly stronger in UCP1+/+. Thus, FGF21 sensitizes DIO mice to the BG-lowering effect of adrenergic stimulation while it prevents ectopic lipid accummulation. The drop of BG is observed even in the absence of UCP1, but UCP1 activity is required to reach the maximal BG-lowering effect of the combination. Disclosure P.Zouhar: None. Funding Czech Science Foundation (19-05356Y)

Impact of dietary vitamin A deficiency on body physiology and liver metabolism of Wistar rats.

Background: Studies suggest that vitamin A deficiency (VAD) can cause night blindness or xerophthalmia, hepatic and metabolic changes in the blood. Aim: Therefore, this work aimed to stablish a model of hypovitaminosis A in rats and to evaluate the effects of vitamin A deficiency on metabolic and oxidative parameters in the liver of rats. Methods: Male (n = 19), Wistar, rats (21-day-old) weighing 50g, divided into two experimental groups: Control Group (C), received AIN 93G diet and Vitamin A Deficiency Group (VAD), received AIN 93G vitamin A-free diet for 45 days. In this work, the parameters analyzed were: body mass, food and water intake, biochemical aspects in the blood, lipids and glycogen content, lipid peroxidation, carbonyl proteins and catalase activity in the liver. Results: In the VAD group, final body mass (9%), liver mass (28%), glycemia (14%), Total -cholesterol (17%), HDL -cholesterol (31%) and VLDL -cholesterol (30%) showed reduced (p < 0.05). The liver lipid (64%) and glyceride-fatty acid (74%) contents were higher in the VAD group. The carbonyl proteins in liver were increased by 171% (p < 0.05). Conclusion: In summary, these results suggest that the absence of vitamin A from the diet was effective in inducing characteristics of hypovitaminosis A in rats. This way, can be used for studies related to glucose and lipid metabolism.

IMPACT OF ORGANOPHOSPHATE PESTICIDE ROGOR ON BIOCHEMICAL PARAMETERS OF FRESHWATER CATFISH Clarias magur (HAMILTON, 1822)

Pesticides are not only dangerous to the environment, but also hazardous to a person's health. Studies on pesticides have clearly established their link to cancer, Alzheimer's Disease, ADHD, birth defects and many more. Rogor is one of the organophosphates extensively used in agricultural practice. It is highly soluble in water for which it can easily enter into the nearby water sources and affect aquatic organisms. In the present study we have planned to observe the effects of rogor in some biochemical parameters in freshwater cat fish Clarias magur. Based on the LC50, we used two sub-lethal concentrations of Rogor - 1/5th (i.e; 13 mg/L) and 1/10th (i.e; 6.5mg/L) in our experiment. After 7 consecutive days of treatment, we have observed a dose dependent decrease in protein, glycogen and lipid content in both liver and muscle of the treated fishes. The amount of protein, glycogen and lipid was decreases with the increasing concentration of the rogor and the results were significant at 0.1 (P&lt;0.1). The amount of blood glucose and total blood cholesterol was also decreases with increasing concentration of rogor.

An Underlying Mechanism by which Hepatic Steatosis Drives the Development of Hypertension

Hepatic steatosis, a consequence of obesity, is closely associated with metabolic and cardiovascular diseases, including hypertension. Even in patients that are not hypertensive, the amount of fat in the liver is positively associated with blood pressure. We hypothesized there was an underlying mechanism linking excess fat in the liver with increased blood pressure. We have previously established that liver lipid content is positively associated with hepatic production and release of the inhibitory neurotransmitter GABA, a process dependent on both the GABA shunt and electrogenic GABA transporters. Because GABA is co‐transported with 1‐2 net positive charges, hepatocyte depolarization, common in obesity, encourages hepatocyte GABA release. To investigate the effect of hepatocyte depolarization, we used an adeno‐associated virus to induce hepatocyte specific expression of an artificial chimeric channel that opens in the presence of an exogenous ligand causing depolarization. Inducing hepatocyte depolarization increases release of GABA and decreases hepatic vagal afferent nerve activity. We established that administering the depolarizing ligand acutely (15‐40 minutes after IP administration) increased systolic (30.08 ± 5.6 mmHg), diastolic (16.47 + 4.3 mmHg), and mean blood pressure (17.85 + 4.4 mmHg) measured via telemetry devices. In hepatic vagotomized mice hepatocyte depolarization had no effect on blood pressure, establishing the key role of afferent hepatic vagal signals in regulating blood pressure. Pharmacological inhibition of the GABA shunt by daily administration of ethanolamine‐O‐sulfate (4 days; 8 mg/mouse/day) limited liver slice GABA release and decreased systolic, diastolic, and mean (10 ± 3.07 mmHg; P &lt; 0.05) blood pressure in diet‐induced obese mice during the first hour of the dark cycle. We subsequently knocked down GABA‐transaminase with bi‐weekly IP deliver of an anti‐sense oligonucleotide targeted to GABA‐transaminase (12.5 mg/kg). We have previously established that this decreases liver GABA‐transaminase mRNA expression by 97% without affecting mRNA expression in the pancreas or brain. GABA‐transaminase knockdown decreased 24h mean, systolic, and diastolic blood pressure (17 + 3, 20 +2, and 14 + 4 mmHg respectively) in obese, angiotensin II induced hypertensive (continuous delivery of angiotensin II 800 ng/kg/min by Alzet® osmotic minipump) male mice. Together this data supports a role of hepatocyte GABA production and release in the hypertension that accompanies obesity. Moreover, our results provide a mechanism by which hepatic lipid content can affect blood pressure, identifying potential targets for the treatment and prevention of obesity‐induced hypertension.

Inhibiting TET1 alleviates non‐alcoholic liver disease progression by targeting lipid metabolic pathways.

Background &amp; AimNon‐alcoholic fatty liver disease (NAFLD) affects more than one‐quarter of adults worldwide, with 60% in diabetic patients and 90% in obese people. Epigenetic modifications are highly associated with NAFLD development. It has been reported that the 5‐hydroxymethylcytosine (5hmC) epigenetic modification and its catalyzing enzymes, the Ten‐eleven translocation (TET) family dioxygenases, are involved in NAFLD progression. However, it remains unclear how the TET family enzymes participate in NAFLD development. The current study was aimed to clarify the involvement of TET family proteins in NAFLD.MethodsGenetic TET1 knockout mice were generated and challenged with a high fat diet (HFD) for 16 weeks. Liver and serum lipid contents were analyzed by biochemical assays. To determine liver injuries, histological staining and liver functional assays were used. Immunoblotting and RNA sequencing were adopted for the study of molecular mechanisms associated with TET‐mediated NAFLD.ResultsThe HFD challenge led to significant down‐regulation of TET1 and TET3 in male mice, but a greater extent in TET1. Thus, TET1 knockout (KO) male mice were generated to evaluate how TET1 KO impacts NAFLD development. TET1 KO decreased mouse body weight without affecting the ratio of liver weight over body weight and fat weight over body weight, suggesting that TET1 KO may not significantly impact the development of liver and adipose tissue. Unexpectedly, TET1 KO substantially suppressed HFD‐induced steatosis and liver injuries.Mechanism studies revealed that the TET1‐mediated fatty liver development is not related to food/water consumption and fed glucose levels. Although the crucial metabolic regulators, including Akt and AMPK/LKB1 signaling pathways, are highly disrupted by the HFD feeding, no differences between TET1 wild‐type and KO mice were found. Interestingly, serum cholesterol, hepatic triglyceride, and cholesterol were substantially decreased in TET1 KO mice. The RNA sequencing results illustrated significant down‐regulation of those genes involved in lipid, fatty acid, and cellular lipid metabolic processes in TET1 KO mice. With further bioinformatics analysis, it was found that substantial down‐regulation of PPARγ, CD36, and ABCG1 in TET1 KO mice may contribute to the alleviation of NAFLD progression. The functions of PPARγ, CD36, and ABCG1 are highly associated with fatty acid synthesis, uptake, and cholesterol synthesis and efflux, respectively, thus supporting the role of TET1 in NAFLD development through targeting lipid metabolic pathways.ConclusionWe demonstrated that TET1 down‐regulation plays a protective role in NAFLD progression by targeting lipid metabolism.

Acipimox Induces the Hepatic Accumulation of Long‐Chain Diacylglycerides and Triglycerides in Severely Burned Sprague Dawley Rats

ObjectivePersistent lipolysis is a hallmark of severe burns, contributing to futile triglyceride cycling and the accumulation of lipid in ectopic tissues. It has been suggested that the administration of acipimox, a potent inhibitor of lipolysis, may blunt the hypermetabolic response to burns. However, what impact massive burns has on the accumulation of individual lipid species in the liver and how this is affected by acipimox treatment is unknown.HypothesisWe hypothesize that large burns results in the accumulation of lipotoxic species within the liver and that this can be prevented by administering acipimox.MethodsThirty‐two male Sprague Dawley rats were randomized to receive either a scald burn (~60% total body surface area) or sham procedure, performed under isoflurane general anesthesia. Afterwards, animals were further randomized to receive either acipimox (50 mg/kg/day) or vehicle (saline) by i.p. injection administered once a day for 7 days. On day 7, animals were euthanized and the liver snap frozen in liquid nitrogen. Liver lipids were extracted by using a chloroform:methanol (2:1) solution and diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA) and cholesterol esters (CE) separated by thin‐layer chromatography. Afterwards, individual lipid classes were esterified to methyl esters, derivatized using heptane, and analyzed by gas chromatography (GC). The fatty acids C16:0, C18:0, cis/trans C18:1, cis 18:2, C20:0, C22:0, C24:0, and C22:6 were resolved by GC for each of the lipid classes examined.ResultsLiver weights were comparable between groups. Burn injury had no significant effect on the concentration of liver lipids compared to sham treated animals, irrespective of lipid class (P &gt; 0.05). In contrast, the administration of acipimox significantly increased liver C16:0 (2.1‐fold; P &lt; 0.05), trans C18:1 (2.5‐fold; P &lt; 0.05), and cis C18:2 (5.5‐fold; P &lt; 0.05) TAG content in burned animals, when compared to injured animals treated with vehicle. No effect of acipimox on liver lipids was observed in sham treated animals.ConclusionContrary to expectations, acipimox causes the accumulation of long‐chain TAGs in rat liver following massive burns, but this is not observed in response to burn injury alone. The ability of acipimox to cause unwanted hepatic metabolic side effects warrants further investigation before it is used clinically to treat massive burns.

Evaluation of the prevention of fat accumulation efficacy of sweet potato fermented products in vivo

Over-nutrition rather than under-nutrition is an important public health challenge in some developed countries. However, the under-nutrition is a major problem according to the global perspective. Therefore, the research and development (R&amp;D) of agricultural functional materials or products for the prevention of fat accumulation is urgently needed. In this experiment, Sprague Dawley (SD) rats in the normal control group were fed with the normal composition for 8 weeks during the experiment. SD rats in the negative control group and three sweet potato fermented products (SPFP) groups were fed a high fat diet for 8 weeks during the experiment. According to the experimental design, three doses SPFP [250, 500, and 1,000 mg/kg body weight (BW)] will be administered after 4 weeks of feeding the high fat diet. During the experiment, BW of the SD rats was recorded every week and blood, liver, and body fat were collected for analysis of body fat rate, blood lipid content, blood glucose content, liver lipid content, and liver and renal functions. Based on the results, the consumption of SPFP does not affect liver and kidney functions, indicating that SPFP is a safe and edible agricultural material. BW change of the normal control group was significantly lower than that of the negative control group and three SPFP groups (p &lt; 0.05). In addition, there was no significant difference in the BW change rate among the groups eat the high fat feed (p &gt; 0.05), but the trend of BW change rate in the low and middle doses of SPFP groups was lower than that in the other high fat feed groups. The food utilization rate of the high fat diet group was significantly higher than that of the normal diet group (p &lt; 0.05). The body fat rate of the normal control group was significantly lower than that of the high fat feed groups (p &lt; 0.05). There was no significant difference between the high fat feed groups (p &gt; 0.05). However, the trend showed that the body fat rate of the low and middle doses of SPFP groups were lower than that of the negative control group and the high dose of SPFP group. In addition, the results of other measurement indicators such as blood lipid content, blood glucose content, and liver lipid content did not show any negative effects of SPFP. Based on the above results, although SPFP on the prevention of body fat accumulation was not significantly exhibited, however, the trend shows that the low and middle doses of SPFP can decrease body fat production. Taken these results together, SPFP may has the potential for the prevention of fat accumulation.

Dietary l-carnitine regulates liver lipid metabolism via simultaneously activating fatty acid β-oxidation and suppressing endoplasmic reticulum stress in large yellow croaker fed with high-fat diets.

Dietary l-carnitine (LC) is a nutritional factor that reduces liver lipid content. However, whether dietary LC can improve lipid metabolism via simultaneous activation of mitochondrial fatty acid (FA) β-oxidation and suppression of endoplasmic reticulum (ER) stress is still unknown. Large yellow croaker were fed with a high-fat diet (HFD) supplemented with dietary LC at 0, 1·2 or 2·4 ‰ for 10 weeks. The results indicated that a HFD supplemented with LC reduced the liver total lipid and TAG content and improved serum lipid profiles. LC supplementation administered to this fish increased the liver antioxidant capacity by decreasing serum and liver malondialdehyde levels and enhancing the liver antioxidant capacity, which then relieved the liver damage. Dietary LC increased the ATP dynamic process and mitochondrial number, decreased mitochondrial DNA damage and enhanced the protein expression of mitochondrial β-oxidation, biogenesis and mitophagy. Furthermore, dietary LC supplementation increased the expression of genes and proteins related to peroxisomal β-oxidation and biogenesis. Interestingly, feeding fish with LC-enriched diets decreased the protein levels indicative of ER stress, such as glucose-regulated protein 78, p-eukaryotic translational initiation factor 2a and activating transcription factor 6. Dietary LC supplementation downregulated mRNA expression relative to FA synthesis, reduced liver lipid and relieved liver damage through regulating β-oxidation and biogenesis of mitochondria and peroxisomes, as well as the ER stress pathway in fish fed with HFD. The present study provides the first evidence that dietary LC can improve lipid metabolism via simultaneously promoting FA β-oxidation capability and suppressing the ER stress pathway in fish.

Dietary calcium pyruvate could improve growth performance and reduce excessive lipid deposition in juvenile golden pompano (Trachinotus ovatus) fed a high fat diet.

Excessive lipid deposition in farmed fish is a challenge in the aquaculture industry. To study the effect of dietary calcium pyruvate (CaP) on lipid accumulation in fish, we used a high fat diet (HFD) to establish a lipid accumulation model in juvenile golden pompano (Trachinotus ovatus) and supplemented with 0%, 0.25%, 0.50%, 0.75% and 1.0% CaP (diets D0-D4, respectively). After 8-week feeding in floating cages, dietary CaP significantly improved growth performance, which peaked in fish fed diet D3. Supplementation of CaP significantly decreased whole body lipid content in fish fed D2-D4 and hepatosomatic index and liver lipid content in fish fed D3 and D4. Serum and hepatic antioxidant indices, including glutathione, catalase and superoxide dismutase, showed generally increasing trends in fish fed diets with CaP. In addition, increasing dietary CaP increasingly reduced hepatic activities of hexokinase, phosphofructokinase and pyruvate kinase involved in glycolysis, and increased glycogen contents of the liver and muscle. Dietary CaP up-regulated the liver mRNA expression of pparα, cpt1, hsl and fabp1, but down-regulated expression of srebp-1, fas and acc. In conclusion, 0.75% CaP improved growth performance and reduced excessive lipid deposition by affecting fatty acid synthesis and lipolysis in juvenile T. ovatus fed HFD.

Bacillus subtilis Supplementation in a High-Fat Diet Modulates the Gut Microbiota and Ameliorates Hepatic Lipid Accumulation in Grass Carp (Ctenopharyngodon idella)

To study the effects of Bacillus subtilis supplementation in a high-fat diet on the gut microbiota and nonalcoholic fatty liver disease in grass carp (Ctenopharyngodon idella), juveniles (60 ± 5 g) were fed three diets: (a) a control diet (CON), (b) a high-fat diet (HFD) and (c) a high-fat diet supplemented with B. subtilis (HFD + BS). After 8 weeks of feeding, fish growth, serum biochemical indices and total liver lipid content were measured, and gut microbiota analysis was performed using the MiSeq250 high-throughput sequencing platform. The results of this study showed that B. subtilis could improve growth and blood serum indices and reduce lipid deposition in the fish liver, preventing fatty liver disease. A grass carp model of fatty liver induced by a high-fat diet was successfully established. Moreover, B. subtilis altered the intestinal microbiota of HFD-fed grass carp, making it more similar to that of the control group. This study revealed the important effects of B. subtilis on grass carp with fatty liver induced by a high-fat diet and provides the foundation for the application of probiotics in grass carp farming.