The effect of various high-fat diet on liver histology in the development of NAFLD models in mice

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD) is exceptionally common around the world. The development of NAFLD is increasing rapidly in the world, along with changes in lifestyle. Excess lipid intake is one of the risk factors for NAFLD. The NAFLD model is induced by a high-fat diet contains SFA, MUFA, and ῳ-6 PUFA. This study aims to assess the effect of high-fat diet variation on liver histology in developing NAFLD models in mice. Methods Thirty-six male mice (Balb/c) were divided into six groups fed a high-fat diet containing beef tallow 60%, beef tallow 45%, vegetable ghee, animal ghee + corn oil, vegetable ghee + corn oil for 28 days and compared to a control group fed a chow diet. All of the mice were fed with a high-fat diet in the form of pellets ad libitum for 28 days. Bodyweight and food intake were measured every day. At the last day of treatment, animals were sacrificed and the Liver were taken for histological analysis. Results This study showed that NAFLD model development was achieved in all group mice fed a high-fat diet with different degrees of NAFLD. Beef tallow 60% had the worst liver histology. Conclusions Thus, based on this study, we found that high-fat diet variations influenced the development of NAFLD models in mice, particularly concerning liver histology.

Download Full-text

Systemic Overexpression of GDF5 in Adipocytes but Not Hepatocytes Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver in Mice

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2021/8894685 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yan Yang ◽

Wenting Zhang ◽

Xiaohui Wu ◽

Jing Wu ◽

Chengjun Sun ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Fatty Liver ◽

High Fat Diet ◽

Lentiviral Vector ◽

Cell Model ◽

Control Group ◽

High Fat ◽

Fatty Acid Binding ◽

Nonalcoholic Fatty Liver

Objective. Our recent study demonstrated that growth differentiation factor 5 (GDF5) could promote white adipose tissue thermogenesis and alleviate high-fat diet- (HFD-) induced obesity in fatty acid-binding protein 4- (Fabp4-) GDF5 transgenic mice (TG). Here, we further investigated the effects of systemic overexpression of the GDF5 gene in adipocytes HFD-induced nonalcoholic fatty liver disease (NAFLD). Methods. Fabp4-GDF5 TG mice were administered an HFD feeding. NAFLD-related indicators associated with lipid metabolism and inflammation were measured. A GDF5 lentiviral vector was constructed, and the LO2 NAFLD cell model was induced by FFA solution (oleic acid and palmitic acid). The alterations in liver function, liver lipid metabolism, and related inflammatory indicators were analyzed. Results. The liver weight was significantly reduced in the TG group, which was in accordance with the significantly downregulated expression of TNFα, MCP1, Aim2, and SREBP-1c and significantly upregulated expression of CPT-1α and ACOX2 in TG mouse livers. Compared to that of cells in the FAA-free control group, LO2 cells with in situ overexpression of GDF5 developed lipid droplets after FFA treatment; the levels of triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly increased in both the GDF5 lentivirus and control lentivirus groups compared with those of the FAA-free group. Additionally, the levels of FAS, SREBP-1, CPT-1α, and inflammation-associated genes, such as ASC and NLRC4, were unaltered despite GDF5 treatment. Conclusion. Systemic overexpression of GDF5 in adipose tissue in vivo significantly reduced HFD-induced NAFLD liver damage in mice. The overexpression of GDF5 in hepatocytes failed to improve lipid accumulation and inflammation-related reactions induced by mixed fatty acids, suggesting that the protective effect of GDF5 in NAFLD was mainly due to the reduction in adipose tissue and improvements in metabolism. Hence, our study suggests that the management of NAFLD should be targeted to reduce the overall amount of body fat and improve metabolic status before the progression to nonalcoholic steatohepatitis occurs.

Download Full-text

Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00419.2013 ◽

2014 ◽

Vol 306 (7) ◽

pp. R499-R509 ◽

Cited By ~ 14

Author(s):

Yada Treesukosol ◽

Bo Sun ◽

Alexander A. Moghadam ◽

Nu-Chu Liang ◽

Kellie L. Tamashiro ◽

...

Keyword(s):

Opioid Receptor ◽

High Fat Diet ◽

Corn Oil ◽

Sucrose Concentration ◽

Maternal Diet ◽

Female Offspring ◽

Chow Diet ◽

High Fat ◽

Endogenous Opioid ◽

Pregnancy And Lactation

Maternal high-fat diet appears to disrupt several energy balance mechanisms in offspring. Here, female offspring from dams fed a high-fat diet (HF) did not significantly differ in body weight compared with those fed chow (CHOW), when weaned onto chow diet. Yet when presented with both a chow and a high-fat diet, high-fat intake was significantly higher in HF compared with CHOW offspring. To assess taste-based responsiveness, offspring (12 wk old) were tested in 30-min sessions (10-s trials) to a sucrose concentration series in a brief-access taste test. Compared with CHOW, the HF offspring initiated significantly fewer trials but did not significantly differ in the amount of concentration-dependent licking. Thus, rather than affect lick response (consummatory), maternal diet affects spout approach (appetitive), which may be attributed to motivation-related mechanisms. Consistent with this possibility, naltrexone, an opioid receptor antagonist, further reduced trial initiation, but not licking in both groups. With naltrexone administration, the group difference in trial initiation was no longer evident, suggesting differences in endogenous opioid activity between the two groups. Relative expression of μ-opioid receptor in the ventral tegmental area was significantly lower in HF rats. When trial initiation was not required in one-bottle intake tests, no main effect of maternal diet on the intake of sucrose and corn oil emulsions was observed. Thus, the maternal high-fat diet-induced difference in diet preference is not likely due to changes in the sensory orosensory component of the taste stimulus but may depend on alterations in satiety signals or absorptive mechanisms.

Download Full-text

Reversal of Diet-Induced Obesity Increases Insulin Transport into Cerebrospinal Fluid and Restores Sensitivity to the Anorexic Action of Central Insulin in Male Rats

Endocrinology ◽

10.1210/en.2012-1929 ◽

2013 ◽

Vol 154 (3) ◽

pp. 1047-1054 ◽

Cited By ~ 35

Author(s):

Denovan P. Begg ◽

Joram D. Mul ◽

Min Liu ◽

Brianne M. Reedy ◽

David A. D'Alessio ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Food Intake ◽

High Fat Diet ◽

Male Rats ◽

Control Group ◽

Chow Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Insulin Transport ◽

The Central Nervous System

Abstract Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

Download Full-text

AFomitopsis pinicola JesengFormulation Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/7312472 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10

Author(s):

Hoe-Yune Jung ◽

Yosep Ji ◽

Na-Ri Kim ◽

Do-Young Kim ◽

Kyong-Tai Kim ◽

...

Keyword(s):

Fatty Liver ◽

High Fat Diet ◽

Cholesterol Biosynthesis ◽

Viscum Album ◽

Control Group ◽

High Fat ◽

Fomitopsis Pinicola ◽

Acanthopanax Senticosus ◽

Nonalcoholic Fatty Liver ◽

Diet Induced Obesity

This study investigated the antiobesity effect of an extract of the Fomitopsis pinicola Jeseng-containing formulation (FAVA), which is a combination of four natural components:Fomitopsis pinicola Jeseng;Acanthopanax senticosus;Viscum album coloratum; andAllium tuberosum. High-fat diet- (HFD-) fed male C57BL/6J mice were treated with FAVA (200 mg/kg/day) for 12 weeks to monitor the antiobesity effect and amelioration of nonalcoholic fatty liver diseases (NAFLD). Body and white adipose tissue (WAT) weights were reduced in FAVA-treated mice, and a histological examination showed an amelioration of fatty liver in FAVA-treated mice without decreasing food consumption. Additionally, FAVA reduced serum lipid profiles, leptin, and insulin levels compared with the HFD control group. The FAVA extract suppressed lipogenic mRNA expression levels from WAT concomitantly with the cholesterol biosynthesis level in the liver. These results demonstrate the inhibitory effects of FAVA on obesity and NAFLD in the diet-induced obese (DIO) mouse model. Therefore, FAVA may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet.

Download Full-text

Ameliorative Effects of Oral Glucosamine on Insulin Resistance and Pancreatic Tissue Damage in Experimental Wistar rats on a High-fat Diet

Comparative Medicine ◽

10.30802/aalas-cm-21-000009 ◽

2021 ◽

Author(s):

Cornelio Barrientos ◽

Angélica Pérez ◽

Jorge Vázquez

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Wistar Rats ◽

Fatty Infiltration ◽

Pancreatic Tissue ◽

Protein Glycosylation ◽

Control Group ◽

Chow Diet ◽

High Fat ◽

Nuclear Pyknosis

Hyperlipidemia due to a high-fat diet (HFD) is a risk factor for inducing insulin resistance (IR) and adverse effects onpancreatic β-cells in obesity and type 2 diabetes mellitus. This relationship may be due to activation of the hexosaminebiosynthesis pathway. Administration of exogenous glucosamine (GlcN) can increase the end product of this pathway(uridine-5′-diphosphate-N-acetyl-glucosamine), which can mediate IR and protein glycosylation. The objective of this study was to evaluate the effects of oral GlcN and HFD on IR and pancreatic histologic damage in a 22 wk study of 4 groups of male Wistar rats: control group with normal chow diet, HFD group (24%. g/g lard), GlcN group (500 mg/kg−1 per day of glucosamine hydrochloride in drinking water) and HFD plus oral GlcN. Metabolic variables related to IR that were measured included triglycerides (TG), free fatty acids (FFAs) and malondialdehyde (MDA). Histopathologic evaluation of the pancreas was also performed. The results showed IR in the HFD group, which had increased pancreatic nuclear pyknosis and vacuolization, with fatty infiltration and structural alteration of the islets of Langerhans. TG, FFAs and MDA were higher in serum and pancreatic tissue as compared with the control group. The GlcN group did not develop IR and had only mild nuclear pyknosis with no significant change in the pancreatic content of TG, FFAs and MDA. However, the combined administration of GlcN and HFD attenuated IR and improved TG, FFAs and MDA levels in serum and pancreatic tissue and the pancreatic histopathologic changes, with no significant differences as compared with the control group. These findings suggest that the oral GlcN at a dose of 500 mg/kg−1 is protective against IR and the pancreatic histologic damage caused by HFD.

Download Full-text

Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

BioMed Research International ◽

10.1155/2018/5045182 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Xiaoqing Ma ◽

Wenhua Du ◽

Shanshan Shao ◽

Chunxiao Yu ◽

Lingyan Zhou ◽

...

Keyword(s):

Er Stress ◽

High Fat Diet ◽

Hepg2 Cells ◽

Liver Weight ◽

Chow Diet ◽

High Fat ◽

Western Blots ◽

Nonalcoholic Fatty Liver ◽

Expression Levels

Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.

Download Full-text

Jiangzhi Ligan Decoction Alleviated Nonalcoholic Fatty Liver Disease Induced by High-Fat-Diet in Rats via GSDMD-mediated Canonical/Non-canonical Pyroptosis Pathway

10.21203/rs.3.rs-250732/v1 ◽

2021 ◽

Author(s):

XIAO ZHOU ◽

Kangkang Yin ◽

Wei Jiang ◽

Ziwei Dai ◽

Biao Tang

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Liver Lipid ◽

Normal Control Group ◽

Control Group ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Hepatoprotective Effects

Abstract Background Hepatoprotective effects of Chinese herbal formula Jiangzhi Ligan Decoction (JZLGD) against nonalcoholic fatty liver disease (NAFLD) have been demonstrated, but its mechanism is not clear. The aim of this study was to evaluate the protective effects of against high-fat diet (HFD) induced NAFLD in rat, and to further explore the potential molecular mechanism. Methods SD rats were assigned to five different groups: normal control group, NAFLD model group and JZLGD-treated NAFLD group (3 doses of JZLGD: 2.3, 4.6, 9.2 g/kg of body weight, respectively). All the rats were fed a HFD for 18 weeks except the normal control group(a normal diet). After 12 weeks, rats in JZLGD-treated NAFLD group were administered different doses of JZLGD by oral gavage once daily for another period of 6 weeks, and the rest were given the same dosage of normal saline. After the intervention, blood and liver from each sample were carefully removed and analyzed accordingly. Results We found that JZLGD significantly reduced the liver index, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. Furthermore, pathological examinations showed that JZLGD markedly reduced liver lipid droplets and improved liver lipid accumulation, NAFLD activity score and ballooning pathology scoring were also decreased. The detection of cytokines showed that JZLGD could significantly reduced the levels of serum inflammatory factors IL-1β, IL-18, tumor necrosis factor α (TNF-α) and IL-6, protected HFD rats from inflammation. In addition, NAFLD treatment, exhibited significant reduction in serum triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and free fatty acid (FFA) when compared to NAFLD control rats. JZLGD intervention also reduced the level of serum lipopolysaccharide (LPS) and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, caspase-11, GSDMD, GSDMD N-terminus (GSDMD-N), IL-1β, IL-18 in the liver. Conclusion These results demonstrate the hepatoprotective effects of JZLGD in NAFLD mice, the effects may be mediated via downregulation of NLRP3 /caspase-1/GSDMD mediated canonical pyroptosis pathway and LPS /caspase-11/GSDMD mediated non-canonical pyroptosis pathway.

Download Full-text

Fenofibrate Alleviates Insulin Resistance and Hepatic Steatosis via Modulation of let-7/ SERCA2b Axis

10.21203/rs.3.rs-83279/v1 ◽

2020 ◽

Author(s):

Dan Zhang ◽

Shan-zhuang Niu ◽

Yi-cheng Ma ◽

Bo Zhou ◽

Yi Deng ◽

...

Keyword(s):

Insulin Resistance ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Luciferase Reporter ◽

Control Group ◽

Chow Diet ◽

High Fat ◽

Alcoholic Fatty Liver

Abstract Background: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist, which is widely used in clinical practice to effectively ameliorates the development of NAFLD. However, the molecular mechanism remains largely unknown, the present study aimed to investigate the role and specific mechanism of fenofibrate on lipid metabolism disorders associated diseases.Methods: The male C57BL6/J mice were divided into 3 groups, the mice in control group (n=10) were fed with normal chow diet, and the mice in HFD-fed group (n =10) were fed with a high fat diet (HFD) for 14 weeks. For the fenofibrate +HFD-fed group (n =10), the mice fed HFD were orally gavaged with fenofibrate (40 mg/kg) daily for the last 4 weeks. Body weight and hip width were measured. Macrosteatosis and fat deposition in the liver were measured by H&E staining and Oil red O staining individually. The levels of serum and hepatic triglyceride were measured, and HOMA-IR, HOMA-ISI were analyzed. The levels of SCD-1, Bip, CHOP and SERCA2b were measured by western blotting. The expression of let-7 were analyzed by qPCR, and the complementarity between the 3′-UTR of SERCA2b gene and let-7 was measured by luciferase reporter assay.Results: Fenofibrate reduces hepatic steatosis and insulin resistance in HFD-fed mice. Fnofibrate alleviates endoplasmic reticulum stress (ER stress) of mice fed a high fat diet (HFD). Fenofibrate increases the levels of Sarco-endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) which serves as a regulator of ER stress. Further, the levels of let-7 microRNA is also regulated by fenofibrate, and let-7 directly targets 3’-UTR of SERCA2b. Conclusion: The present data suggests that fenofibrate alleviates ER stress through the let-7/SERCA2b axis to protect against excessive lipid accumulation in the liver of Non-alcoholic fatty liver disease (NAFLD) mice.

Download Full-text

Lentinan Protects against Nonalcoholic Fatty Liver Disease by Reducing Oxidative Stress and Apoptosis via the PPARα Pathway

Metabolites ◽

10.3390/metabo12010055 ◽

2022 ◽

Vol 12 (1) ◽

pp. 55

Author(s):

Tingyi Du ◽

Qin Fang ◽

Zhihao Zhang ◽

Chuanmeng Zhu ◽

Renfan Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Chow Diet ◽

Protective Effects ◽

High Fat ◽

Nonalcoholic Fatty Liver

Aim: Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. Methods: C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). Results: After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. Conclusion: In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.

Download Full-text

Gegen Qinlian Decoction Attenuates High-Fat Diet-Induced Steatohepatitis in Rats via Gut Microbiota

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/7370891 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Yi Guo ◽

Pang-hua Ding ◽

Li-juan Liu ◽

Lei Shi ◽

Tang-you Mao ◽

...

Keyword(s):

Gut Microbiota ◽

Group Treatment ◽

High Fat Diet ◽

Metabolic Diseases ◽

Intestinal Flora ◽

Underlying Mechanism ◽

Control Group ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Traditional Chinese Herbal Medicine

Gut microbiota play an important role in modulating energy contribution, metabolism, and inflammation, and disruption of the microbiome population is closely associated with chronic metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD). Gegen Qinlian decoction (GGQLD), a well-known traditional Chinese herbal medicine (CHM), was previously found to regulate lipid metabolism and attenuate inflammation during NAFLD pathogenesis. However, the underlying mechanism of this process, as well as how the gut microbiome is involved, remains largely unknown. In this study, we investigated the effect of varying doses of GGQLD on the total amount and distribution of gut bacteria in rats fed a high-fat diet (HFD) for 8 weeks. Our analysis indicates that Oscillibacter and Ruminococcaceae_g_unclassified are the dominant families in the HFD group. Further, HFD-dependent differences at the phylum, class, and genus levels appear to lead to dysbiosis, characterized by an increase in the Firmicutes/Bacteroidetes ratio and a dramatic increase in the Oscillibacter genus compared to the control group. Treatment with GGQLD, especially the GGQLL dose, improved these HFD-induced changes in intestinal flora, leading to increased levels of Firmicutes, Clostridia, Lactobacillus, bacilli, and Erysipelotrichales that were similar to the controls. Taken together, our data highlight the efficacy of GGQLD in treating NAFLD and support its clinical use as a treatment for NAFLD/NASH patients.

Download Full-text