Farnesoid X receptor （FXR） is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms： 1） FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2） FXR promotes liver regeneration and repair after injury; 3） FXR protects liver cells from death and enhances cell survival; 4） FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5） FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer.
Non-alcoholic fatty liver disease （NAFLD） is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor （FXR）, a member of the nuclear receptor （NR） superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia.
The identification of the estrogen-related receptors （ERRs） as the first orphan nuclear receptors ignited a new era in molecular endocrinology, which led to the discovery of new ligand-dependent response systems. Although ERR subfamily members have yet to be associated with a natural ligand, the characterization of these orphan receptors has demonstrated that they occupy a strategic node in the transcriptional control of cellular energy metabolism. In particular, ERRs are required for the response to various environmental challenges that require high energy levels by the organism. As central regulators of energy homeostasis, ERRs may also be implicated in the etiology of metabolic disorders, such as type 2 diabetes and metabolic syndrome. Here, we review the recent evidence that further highlights the role of ERRs in metabolic control, particularly in liver and skeletal muscle, and their likely involvement in metabolic diseases. Consequently, we also explore the promises and pitfalls of ERRs as potential therapeutic targets.
AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH)development in mice fed a methionine-choline-deficient(MCD)diet.METHODS Twenty-four male C57BL/6J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2w group,n=6)or 4 wk(Control 4w group,n=6)or the MCD diet for 2 wk(MCD 2w group,n=6)or 4 wk(MCD 4w group,n=6).Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding.The fecal microbiome and metabolome were studied using 16s rRNA deep sequencing and gas chromatography-mass spectrometry.RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk.After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired.Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium)coprostanoligenes group(P<0.001 and P<0.05,respectively)and a significant increase in Ruminococcaceae UCG 014 abundance(P<0.05)after 2 wk.At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P<0.05,and P<0.01,respectively).The fecal metabolomic profile was also substantially altered by the MCD diet:At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected.CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.
Background:The aim of this study was to determine how maternal undernutrition during pregnancy and offspring birth-weight can affect the postnatal development of offspring under farm conditions,which may lead to consequences in its meat and carcass quality.The current study involved a total of 80 litters from Iberian sows fed a diet fulfilling daily requirements(n=47;control)or providing 70%daily requirements(n=33;underfed)from d 38 to d 90 of gestation when fetal tissue development begins.After birth,piglets born live were classified as low birthweight(LBW;<1 kg)and normal birth-weight(NBW;?1 kg).During the growing phase,240 control and 230 underfed pigs(50%males and females)distributed by BW category and sex were studied until the slaughter.Results:At birth and weaning,there were significant differences in all morphological measures and weight between NBW and LBW piglets as expected(P<0.0005),but few effects of the gestational feed restriction.During the growing phase,NBW pigs continued with higher weight than LBW pigs on all the days of evaluation(P<0.05),even though control-LBW-females and LBW-males showed a catch-up growth.However,underfed pigs showed slower growth and higher feed conversion ratio than control pigs(P<0.0001)at 215 days old.Moreover,the average daily weight gain(ADWG)for the overall period was greater for NBW,male and control pigs than for their LBW,female and underfed pigs(P<0.0001,P<0.0005 and P<0.05,respectively)and NBW pigs were slaughtered at a younger age than LBW pigs(P<0.0001).After slaughtering,control pigs also had higher carcass yield and backfat depth than underfed pigs(P<0.0005)and the maternal nutritional effect caused main changes in the polar lipid fraction of liver and loin.The fatty acid composition of loin in control pigs had higher C18:1n-9 and n-3 FA concentrations,as well as lowerΣn-6/Σn-3 ratio,than in underfed pigs(P<0.005).Conclusions:In brief,results showed that the effects of maternal nutritional restriction appeare...
In the literature there are many reports on the composition and properties of pumpkin seed oil; however, few is known about the effect of different stages of seed development on various fatty acid profiles in developing seeds. The objective of this study was to provide the changes of various fatty acid accumulations in seed oil obtained from the seeds of three pumpkin varieties belonging to the species Cucurbita maxima and Cucurbita pepo. Unsaturated acids (oleic and linoleic) were dominant in various fatty acids, which constituted 38.9%-49.1% and 29.4%-42.7% of the total fatty acids at seed maturity for three pumpkin varieties, respectively, while other fatty acid concentrations except for palmitic acid all did not reach 10%. Different varieties exhibited greater effect on various fatty acid contents and the total fatty acid contents in the seeds of pumpkin rather than the species. On the whole, palmitic acid profiles of the seed oil in three varieties all followed the fluctuant decrease during all the stages of seed development, but palmitoleic acid and the total fatty acid profiles of the seed oil in three varieties were just the opposite. Stearic, oleic and linoleic acid profiles of the seed oil in three varieties all experienced the third pattern that fluctuated during all the stages of seed development, but no significant differences in these three fatty acid concentrations were found from the beginning to the end. Linolenic acid concentrations of three varieties were on the decline and ultimately close to zero. Myristic and arachidic acid profiles of the seed oil followed different trends in three varieties. Among them, myristic and arachidic acid profiles of the seed oil of Yinhui-1 fluctuated downward all the time until seed maturity, but those of 0238-1 and Jinhui-2 completely changed oppositely.
AIM To examine the relationship between serum autotaxin(ATX)concentrations and clinicopathological findings in non-alcoholic fatty liver disease(NAFLD)patients.METHODS One hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled.Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays.Sera obtained from 160 healthy,nonobese individuals were used as controls.Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman’s test.Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve(AUC).Cut-off values were identified by the Youden index,and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTS Serum ATX levels were significantly higher in NAFLD patients than in controls(0.86 mg/L vs 0.76 mg/L,P<0.001)and correlated significantly with ballooning score and fibrosis stage(r=0.36,P<0.001 and r=0.45,P<0.001,respectively).Such tendencies were stronger in female patients.There were no remarkable relationships between ATX and serum alanine aminotransferase,lipid profiles,or steatosis scores.The AUC values of ATX for predicting the presence of fibrosis(?F1),significant fibrosis(?F2),severe fibrosis(?F3),and cirrhosis(F4),were all more than 0.70 in respective analyses.CONCLUSION Serum ATX levels may at least partially reflect histological severity in NAFLD.
AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP)was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L)and fibrosis score(7.4 to 6.1 kPa)(P<0.05).Post-SVR,48 patients(47.5%)had steatosis on CAP;of these,6.25%had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/dL),ALT(20.4 vs 15.3 mg/dL),CAP score(296.3 vs 212.4 dB/m)and fibrosis score(7.0 vs 5.3 kPa);P<0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa);alternatively,(P<0.05)and therefore patients with steatosis continued to have clinically significant stiffness(?7 kPa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV)patients post-SVR.These patients continue to have elevated mean fibrosis score(?7 kPa)compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.
AIM To identify the effect of hydrogen-rich water(HRW)and electrolyzed-alkaline water(EAW)on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1)Regular diet(RD)/regular water(RW);(2)high-fat diet(HFD)/RW;(3)RD/EAW;and(4)HFD/EAW.Weight and body composition were measured.After twelve weeks,animals were sacrificed,and livers were processed for histology and reverse-transcriptase polymerase chain reaction.A similar experiment was performed using HRW to determine the influence and importance of molecular hydrogen(H2)in EAW.Finally,we compared the response of hepatocytes isolated from mice drinking HRW or RW to palmitate overload.RESULTS EAW had several properties important to the study:(1)pH=11;(2)oxidation-reduction potential of-495 mV;and(3)H2=0.2 mg/L.However,in contrast to other studies,there were no differences between the groups drinking EAW or RW in either the RD or HFD groups.We hypothesized that the null result was due to low H2 concentrations.Therefore,we evaluated the effects of RW and low and high HRW concentrations(L-HRW=0.3 mg H2/L and H-HRW=0.8 mg H2/L,respectively)in mice fed an HFD.Compared to RW and L-HRW,H-HRW resulted in a lower increase in fat mass(46%vs 61%),an increase in lean body mass(42%vs 28%),and a decrease in hepatic lipid accumulation(P<0.01).Lastly,exposure of hepatocytes isolated from mice drinking H-HRW to palmitate overload demonstrated a protective effect from H2 by reducing hepatocyte lipid accumulation in comparison to mice drinking regular water.CONCLUSION H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice.