Diet-induced Non-alcoholic Steatohepatitis In Rats Research Articles

Curcumin Alleviates High-fat Diet-induced Nonalcoholic Steatohepatitis via Improving Hepatic Endothelial Function with Microbial Biotransformation in Rats.

Hepatic endothelial function is central to the development of nonalcoholic steatohepatitis (NASH). Curcumin (Cur) is reportedly hepatoprotective, however, it remains unknown whether Cur improves hepatic endothelial function in NASH. Additionally, the poor bioavailability of Cur renders it difficult to elucidate its hepatoprotective effect, hence, its biotransformation should be considered. Herein, we investigated the effects and mechanisms of Cur and its bioconversion on hepatic endothelial function against high-fat diet-induced NASH in rats. The results revealed that Cur improved hepatic lipid accumulation, inflammation, and endothelial dysfunction by inhibiting NF-κB and PI3K/Akt/HIF-1α pathways, however, these effects were weakened via antibiotic addition, which was closely related to reduced tetrahydrocurcumin (THC) produce in the liver and intestinal content. Moreover, THC exerted a better effect than Cur on restoring liver sinusoidal endothelial cells function to attenuate steatosis and injury in L02 cells. Thus, these findings indicate that the effect of Cur on NASH is closely related to hepatic endothelial function improvement with intestinal microbial biotransformation.

Expression of Concern: Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.

Expression of Concern: Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.

The NLRP3 inhibitor and Nrf2 Agonist, RRx-001, Ameliorates Non-alcoholic Fatty Liver Disease in Rats

Lead Author's Financial Disclosures EpicentRx. Study Funding EpicentRx Inc. Background/Synopsis The development and progression of non-alcoholic steatohepatitis (NASH), an increasingly prevalent disease for which no pharmacological therapy has been approved, is linked to oxidative stress, inflammation, and fibrosis of the liver. Here, we investigated the novel mechanism of RRx-001, an NLRP3 inhibitor and Nrf2 agonist, which is in Phase 3 clinical trials for the treatment of cancer, as a therapeutic option for ameliorating NASH in a diet-induced mice model. Objective/Purpose To investigate whether intraperitoneal administration of RRx-001 improved high-fat diet-induced NASH in rats. Methods Sprague-Dawley rats (6-weeks-old male; about 180g weight) were randomly divided into three groups, one subjected to normal diet (ND) and two groups in high-fat, atherogenic diet (HFD, 40 kcal % fat, 1.25% cholesterol, 0.5% sodium cholate) for 12 weeks. One of HFD groups was treated IP with (5 mg/kg of RRx-001 every other week) for the last 8 weeks before characterization. Several markers of inflammation and steatosis were evaluated. Results Every other week administrations of RRx-001 reduced hepatic steatosis scores, serum ALT and AST levels, and hepatic levels of cholesterol and triglycerides in rats fed a high-fat diet. These were correlated with the suppression of NLRP3 inflammasome activation by RRx-001 as evidenced by decreased levels of NLRP3, caspase-1, and IL-1β levels on ELISA. Conclusions The findings of this study demonstrate that RRx-001 reduced inflammation with an anti-lipidemic and anti-NASH effect mediated at least in part by inhibition of the NLRP3 pathway. Thus, targeting the NLRP3 inflammasome with RRx-001 may contribute to the prevention and treatment of NASH. EpicentRx.

β-patchoulene protects against non-alcoholic steatohepatitis via interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation in rats

Non-alcoholic steatohepatitis (NASH), an extreme progressive subtype of metabolic associated fatty liver disease, is well characterized by hepatic steatosis, injury and inflammation. It causes irreversible hepatic damage and there are no approved interventions for it. β-PAE, a representatively pharmacological active substance isolated from Pogostemon cablin, has been indicated to alleviate hepatic steatosis and injury through modulating lipid metabolism in rats with simple steatosis. However, its protection against NASH remains unclear. Here, this study explored the potential effect of β-PAE against high-fat diet-induced NASH in rats. The results displayed that β-PAE significantly reduced the gains of body weight and epididymal adipose tissue, liver index and attenuated liver histological damages in NASH rats. It also markedly alleviated hepatic inflammation by inhibiting NLRP3 inflammasome activation. In NASH, the active NLRP3 inflammasome is caused by hepatic lipid abnormal accumulation-induced oxidative stress. Excessive oxidative stress results in hepatic histanoxia, which exacerbates lipid metabolism disorders by elevating CD36 to suppress AMPK signalling pathways. Moreover, the lipid accumulation led by lipid metabolism dysfunction intensifies oxidative stress. A vicious circle is formed among oxidative stress, histanoxia and lipid accumulation, eventually, but β-PAE effectively interrupted it. Interestingly, soluble CD36 (sCD36) was tightly associated not only with hepatic steatosis and injury but also with inflammation. Collectively, β-PAE exerted a positive effect against NASH by interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation, and sCD36 may be a promising non-invasive tool for NASH diagnosis.

Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model

AimTo investigate the prophylactic efficacy of gut microbiota-based treatments on nonalcoholic steatohepatitis (NASH) management via modulation of Hippo signaling pathway-related genes (YAP1, LATS1 and NF2), and their epigenetic regulators (miR-1205 and lncRNA SRD5A3-AS1) retrieved from in-silico data analysis. Materials & methodsHistopathological, biochemical, molecular and immunohistochemistry analyses were used to assess the effects of multistrain probiotic mixture and prebiotic inulin fiber on high sucrose high fat (HSHF) diet-induced NASH in rats. These treatments were administered orally either alone or in combination, along with HSHF diet. ResultsBoth probiotic mixture and prebiotic inulin fiber attenuated steatosis, inflammation and fibrosis grades in HSHF diet-induced NASH rats. Moreover, the applied treatments significantly prevented the elevation of serum liver enzymes and improved lipid panel. At the molecular level, both treatments down-regulated hepatic YAP1 mRNA and miR-1205 expressions, and concomitantly up-regulated the expression of hepatic LATS1&NF2 mRNAs and the lncRNA SRD5A3-AS1. At the protein level, both treatments decreased the hepatic content of the inflammatory marker IL6 and the fibrotic marker TGFβ1. Moreover, an observable reduction in α-SMA together with noticeable elevation in LATS1/2 protein expression levels were detected in liver sections compared to the untreated rats. ConclusionProbiotic mixture and prebiotic inulin fiber, either alone or in combination, attenuated NASH progression and ameliorated both fibrosis and hepatic inflammation in the applied animal model. The produced effect was correlated with modulation of the retrieved (YAP1, LATS1 and NF2) – (miR-1205) – (lncRNA SRD5A3-AS1) RNA panel.

Camellia sinesis leaves extract ameliorates high fat diet-induced nonalcoholic steatohepatitis in rats: analysis of potential mechanisms

Our research aims to address and determine the effect of Camellia sinensis extract in the management of nonalcoholic steatohepatitis (NASH) in rats. Forty adult female albino rats were divided into four groups. Group 1 (G1) served as the control group, while the other three groups received high-fat diet for 32 weeks to induce NASH and then were later assigned to the following groups: (G2) NASH-afflicted group which was left untreated, (G3) NASH-afflicted group treated with Camellia sinensis extract in a dose of 400 mg/kg, and (G4) NASH-afflicted group treated with Camellia sinensis extract in a dose of 200 mg/kg. Significant elevation in serum alanine aminotransferase, albumin, bilirubin (total and direct), cholesterol, low density lipoprotein, triglycerides, leptin, Cox-2, and CD40 values was recorded. Moreover, overexpression of hepatic tumor necrosis factor alpha and hepatocyte growth factor genes were recorded, whereas blood platelet count and serum high density lipoprotein concentration revealed significant depletion, which was paralleled by significant downregulation of hepatic adiponectin gene expression level in NASH group versus the control group. On the opposite side, treatment of NASH groups with two different doses of Camellia sinensis extract reversed the values of the measured biochemical parameters and the targeted gene expression levels when compared with the NASH group. Optical micrograph of liver tissue sections of rats treated with Camellia sinensis extract showed the observed improvement in the studied biochemical and genetic markers. This study provides a clear evidence for the promising therapeutic potential of Camellia sinensis extract against NASH. This could be ascribed to its hepatoprotective activity, hypolipidemic effect, and anti-inflammatory potency.

Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.

Nicotine, a major compound in cigarette smoke, decreases food intake and body weight gain in mammals; however, the influence of nicotine on the progression of non-alcoholic steatohepatitis (NASH) remains controversial. This study aimed to investigate the effect of nicotine on NASH in rat models. Male Wistar rats were fed choline-deficient, l-amino acid-defined (CDAA) diet and treated with nicotine or saline. Food intake, body weight gain, presence of hepatic steatosis, inflammation, and fibrosis were assessed 6 weeks after the rats were fed CDAA diet. Hepatic branch vagotomy was performed to elucidate the mechanism through which nicotine affected steatohepatitis.CDAA diet induced hepatic steatosis, inflammation, and fibrosis, as well as increased the expression of inflammation-related genes. Conversely, nicotine significantly attenuated food intake, body weight gain, and inhibited the CDAA-diet-induced hepatic steatosis, inflammation, and fibrosis, together with increased expression of inflammation-related genes. Hepatic branch vagotomy by itself decreased food intake, body weight gain, and attenuated the CDAA-diet-induced hepatic steatosis, but not inflammation. However, nicotine did not change the food intake, body weight gain, and CDAA diet-induced hepatic steatosis and inflammation in vagotomized rats. These results suggest that nicotine attenuates the CDAA-diet-induced hepatic steatosis and inflammation through the hepatic branch of the vagus nerve in rats.

Beneficial effects of diacerein on adipokines and pro-inflammatory cytokines involved in diet-induced nonalcoholic steatohepatitis in rats

Background: Non-alcoholic steatohepatitis (NASH) is considered as a progressive liver disease, so effective therapies are needed to ameliorate hepatic steatosis, inflammation and fibrosis, and to prevent the progression to cirrhosis and hepatocellular carcinoma. Diacerein is an anti-inflammatory drug that inhibits the synthesis and activity of pro-inflammatory cytokines. The present study was designed to investigate the effect of diacerein on pro-inflammatory cytokines as well as adipokines involved in diet-induced NASH rat model.Methods: Thirty-two adult male rats were divided into four groups: control, diacerein-treated, NASH-untreated and NASH+diacerein-treated groups. NASH was induced by feeding rats with high-fat and high-cholesterol diet for 12 weeks. Body weight, liver weight, fasting blood glucose and insulin levels for estimation of insulin resistance, blood lipids, alanine transaminase, and aspartate aminotransferase were evaluated. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), adiponectin, visfatin and leptin were also detected. Histopathological examination of liver sections was performed.Results: Diacerein significantly reduced liver weight, fasting blood glucose, insulin level, transaminases and ameliorates insulin resistance with favourable effects on blood lipids. These results were accompanied with a significant reduction in serum levels of TNF-α, IL-1β, IL-6, and visfatin, while, adiponectin was significantly increased and leptin was insignificantly affected. Liver sections revealed that diacerein reduced steatosis and lobular inflammatory grades.Conclusions: These data suggest that diacerein administration may have a potential usefulness in the prevention of NASH as a possible result of inhibition of pro-inflammatory cytokines and the beneficial effects on adipokines especially adiponectin and visfatin.

An ErChen and YinChen Decoction Ameliorates High-Fat-Induced Nonalcoholic Steatohepatitis in Rats by Regulating JNK1 Signaling Pathway.

ErChen and YinChen decoction (ECYCD) is an effective traditional Chinese medicine and has been widely used in traditional Chinese medicine to treat nonalcoholic steatohepatitis (NASH), with good curative effects. However, the specific mechanisms underlying these effects are unclear. In this study, we determined the efficacy of ECYCD in a high-fat diet-induced NASH rat model, established by 8-week administration of a high-fat diet. ECYCD was administered daily for 4 weeks, after which the rats were euthanized. The results demonstrated that ECYCD ameliorated high-fat diet-induced NASH, as evidenced by decreased liver indexes, reduced hepatic lipid deposition and liver injury, lower serum biochemistry markers (including low-density lipoprotein), and reduced HOMA-IR scores. Moreover, levels of free fatty acids, tumor necrosis factor, and malondialdehyde were decreased, whereas glutathione was increased in the liver. Serum high-density lipoprotein was also increased in the liver, and ECYCD regulated the c-Jun N-terminal kinase 1 (JNK1) signaling pathway by decreasing the levels of JNK1 protein, JNK1 mRNA, activator protein- (AP-) 1 protein, AP-1 mRNA, and phospho-insulin receptor substrate- (IRS-) 1ser307 and increasing phopsho-PKBser473 levels. These results suggested that ECYCD could ameliorate high-fat diet-induced NASH in rats through JNK1 signaling. ECYCD may be a safe therapeutic option for the treatment of NASH.

Methionine and Choline Deficient Diet-induced Non-Alcoholic Steatohepatitis in Rats: Role of Melatonin

Methionine and Choline Deficient Diet-induced Non-Alcoholic Steatohepatitis in Rats: Role of Melatonin

Treatment with geraniol ameliorates methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in rats.

Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. The aim of this work was to investigate whether treatment with geraniol (a monoterpene) attenuated NASH induced by methionine-choline-deficient (MCD) diet in rats. Rats were fed with MCD diet to induce NASH and treated with geraniol (200 mg/kg/day) for 10 weeks. Treatment with geraniol reduced histological scores, fibrosis, and apoptosis in livers, lowered activities of alanine aminotransferase and aspartate aminotransferase in serum, and attenuated hepatic fat accumulation in rats fed with MCD diet. Treatment with geraniol preserved hepatic mitochondrial function, evidenced by reduced mitochondrial reactive oxygen species formation, enhanced adenosine triphosphate formation and membrane integrity, restored mitochondrial electron transport chain enzyme activity, and increased mitochondrial DNA content in rats fed with MCD diet. Treatment with geraniol reduced uncoupling protein 2 protein expression, and enhanced protein expression of prohibitin, mRNA expression of peroxisome proliferator-activated receptor α, and activity of mitochondrial carnitine palmitoyl transferase-I in livers of rats fed with MCD diet. Treatment with geraniol abated oxidative stress, evidenced by reduced malondialdehyde and 3-nitrotyrosine formation, enhanced activity of glutathione S-epoxide transferase, and down-regulated expression of inducible nitric oxide synthase and cytochrome P450 2E1 in livers of rats fed with MCD diet. Treatment with geraniol reduced myeloperoxidase activity and protein expression of tumor necrosis factor alpha and IL-6 in livers of rats fed with MCD diet. Treatment with geraniol attenuated MCD-induced NASH in rats.

Treatment with baicalein attenuates methionine−choline deficient diet-induced non-alcoholic steatohepatitis in rats

Baicalein, a naturally occurring flavone, has been proved as a promising chemopreventive compound for many chronic human diseases. The aim of this work was to investigate whether treatment with baicalein prevented nonalcoholic steatohepatitis (NASH) induced by methionine−choline-deficient (MCD) diet. Rats were divided into four experimental groups and fed for 8 weeks as follows: (1) control rats; (2) control rats treated with baicalein (intraperitoneal injection of 10mg/kg); (3) MCD-diet-fed rats; (4) MCD-diet-fed rats treated with baicalein. Treatment with baicalein prevented MCD-diet-induced NASH, as evidenced by reduced histological scores, apoptosis, activities of ALT and AST, and hepatic fat accumulation in rats. Treatment with baicalein abated MCD-diet-induced oxidative stress through enhancing Nrf2/HO-1 pathway and activities of SOD and catalase in livers. Treatment with baicalein preserved hepatic mitochondrial function in MCD-diet fed rats. Treatment with baicalein reduced hepatic NO formation through suppressing MCD-diet-induced iNOS activation, and suppressed MCD-diet-induced inflammation through suppressing NFκB activation and reducing IL-6 and TNFα expressions in livers. Treatment of MCD-diet fed rats with baicalein had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers. The results support the investigation of baicalein as a therapeutic candidate for NASH induced by MCD diet in rats.

Effects of Gegen Qinglian Tang on high-fat diet-induced non-alcoholic steatohepatitis in rats

Effects of Gegen Qinglian Tang on high-fat diet-induced non-alcoholic steatohepatitis in rats

Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats

To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and liver homogenate FFA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial analysis kits. The expression levels of CYP2E1 mRNA and protein were determined using RT-PCR and immunoblot assays, respectively. Tiopronin significantly lowered both the serum ALT and AST levels, while only the serum ALT level was lowered by UDCA. Tiopronin significantly decreased the serum and liver levels of TG, TC and FFA as well as the serum LDL-C level, and increased the serum HDL-C level, while UDCA decreased the serum and liver TC levels as well as the serum LDL-C level, but did not change the serum levels of TG, FFA and HDL-C. Tiopronin apparently ameliorated the hepatocyte degeneration and the infiltration of inflammatory cells in the livers, but UDCA did not affect the pathological features of the livers. Both tiopronin and UDCA ameliorated the mitochondrial abnormality in the livers. The benefits of tiopronin were associated with increased SOD and GSH-Px activities, and with decreased MDA activity and CYP2E1 expression in the livers. Tiopronin exerts protective effects against non-alcoholic steatohepatitis in rats, which may be associated with its antioxidant properties and regulation of lipid metabolism.

Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress

BackgroundNonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. It has been suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. The aim of present study was to determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C could improve the biochemical and histological abnormalities associated with diet-induced NASH in rats.MethodsNASH was induced in male N-Mary rats by feeding a methionine - choline deficient (MCD) diet. The rats were fed either normal chow or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly divided into four groups of six: the NASH group that received MCD diet, the EUK-8 group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK-8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage for eight weeks.ResultsTreatment of MCD-fed rats with salens reduced the sera aminotransferases, cholesterol, low density lipoprotein contents, the extent of lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis, ballooning degeneration and inflammation in liver of MCD-fed rats.ConclusionAntioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced biochemical and histological abnormalities, pointing out that antioxidant strategy could be beneficial in treatment of NASH.

Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress

Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. It has been suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. The aim of present study was to determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C could improve the biochemical and histological abnormalities associated with diet-induced NASH in rats. NASH was induced in male N-Mary rats by feeding a methionine - choline deficient (MCD) diet. The rats were fed either normal chow or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly divided into four groups of six: the NASH group that received MCD diet, the EUK-8 group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK-8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage for eight weeks. Treatment of MCD-fed rats with salens reduced the sera aminotransferases, cholesterol, low density lipoprotein contents, the extent of lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis, ballooning degeneration and inflammation in liver of MCD-fed rats. Antioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced biochemical and histological abnormalities, pointing out that antioxidant strategy could be beneficial in treatment of NASH.

Increased hepatic apoptosis in high-fat diet-induced NASH in rats may be associated with downregulation of hepatic stimulator substance

The mechanisms of progression from fatty liver to steatohepatitis and cirrhosis are not well elucidated. Hepatocellular apoptosis could be one of the key factors in the pathogenesis of non-alcoholic steatohepatitis (NASH). Hepatic stimulator substance (HSS) protects liver cells from various toxins. We previously reported that HSS is critically important for the survival of hepatocytes due to its mitochondrial association. This study aims to investigate the relationship between HSS and hepatocellular apoptosis in vivo models of high-fat diet-induced NASH and in vitro models of palmitic acid-induced hepatocyte injury. Sprague-Dawley rats were fed a high-fat diet for 8, 12 and 16weeks. Hepatic histological lesions, liver function and apoptosis were examined. HSS expression, in association with caspase-3 and cytochrome c leakage, which are both indicators of cell apoptosis, was measured. Results showed that a high-fat diet altered liver function and histology in a manner resembling NASH. Hepatic protein and mRNA HSS expression was decreased as NASH progressed. Meanwhile, cell apoptosis increased as result of caspase-3 activation and cytochrome c release, indicating that HSS might be involved in NASH pathogenesis. Furthermore, in palmitic acid-induced hepatic cell damage, over-expression of HSS decreased cells apoptosis. In contrast, repression of HSS expression by siRNA increased cell apoptosis. In conclusion, these data imply that cell apoptosis contributes to the pathogenesis of NASH, during which HSS expression is downregulated. Increasing HSS expression in hepatocytes may forestall cell apoptosis as result of fatty acid insult.

Neonatal exposure to genistein ameliorates high-fat diet-induced non-alcoholic steatohepatitis in rats

Non-alcoholic steatohepatitis (NASH) is becoming a prevalent disease in developing countries with no effective therapy. Isoflavones such as genistein have been shown to prevent NASH in a rat model, but the effects of neonatal exposure to genistein on lipid metabolism have been rarely studied. In the present study, three doses of genistein (30, 300 or 1200μg/rat per d) were injected (subcutaneously) into neonatal male Sprague-Dawley rats at postnatal days 1-5. After weaning, these rats were allowed free access to a high-fat diet for 6 weeks. The results demonstrate that NASH was induced by high fat feeding in the control rats, whereas genistein-treated rats displayed smaller body weight, and lower hepatic inflammation and steatosis. The mid dose of genistein was most effective. Neonatal exposure to genistein also resulted in a lower incidence of apoptotic cells in the liver. Additionally, neonatal genistein-treated rats showed lower hepatic expression of fatty acid synthase and sterol regulatory element-binding protein-1, but higher expression of PPARα, indicative of lower rates of lipid synthesis and higher rates of β-oxidation. These results indicate that neonatal treatment with genistein has a prolonged effect on hepatic lipid metabolism that is maintained post-weaning, offering a potential approach for the prevention of hepatic steatosis and NASH.