Comprehensive Study of Multiple Stages Progressing to Nonalcoholic Steatohepatitis with Subsequent Fibrosis in SD Rats

Abstract

Because of the absence of the time course of histological nonalcoholic fatty hepatitis with subsequent fibrotic progression, the effective approaches available for controlling the onset and progression of non-alcoholic steatohepatitis (NASH) remain limited. Therefore, we detected the serum and liver tissue related lipid metabolism disorder, liver pathology and relative molecular makers alteration dynamically in a high fat-sucrose diet during different time points. High fat-sucrose diet significantly increased the serum lipid level on day 10. The excess lipid accumulation in liver was referred to as simple steatosis after the feeding of a high fat-sucrose diet for 20 days. The high fat-sucrose diet induced a hepatic inflammation response on day 30. Similarly, hepatic fibrosis was also initiated on day 30 and gradually formed from the 30th to the 50th day. Oxidative stress may be related with the process from NASH to liver fibrosis. Insulin resistance was involved in the progression from hepatic steatosis to NASH with hepatic fibrosis from the 20th to the 50th day. In conclusion, we established a high fat-sucrose diet induced nonalcoholic fatty hepatitis with liver fibrosis rat model, which presented the time course of histological nonalcoholic steatohepatitis and the initiation and progression change of characteristic molecular makers in the process from steatosis to hepatic fibrosis.

Metabolomics Characterizes the Effects and Mechanisms of Quercetin in Nonalcoholic Fatty Liver Disease Development

“…All abovementioned indexes were measured by commercially available kits (Nanjing Jiancheng Bioengineering Institute, Nanjing, China). The experiments were performed as described previously [ 41 ].…”

Gut-Derived Serotonin Contributes to the Progression of Non-Alcoholic Steatohepatitis via the Liver HTR2A/PPARγ2 Pathway

“…Our previous report showed the HFSD induced NASH in rats at day 30 and non-alcoholic fatty liver (NAFL) condition at day 20 (Wang et al, 2017). To further explore whether the depletion of 5-HT could alleviate the pathogenesis of NASH, we applied LP533401 and tryptophan-free diet in this study (Figure 2A).…”

“…Control groups: The rats fed basal diet (360 kcal/100 g, 13.3 g/ 100 g from fat, 26.2 g/100 g from protein, and 60.5 g/100 g from carbohydrate) and sacrificed at 20 days (C20) and at 30 days (C30), Model groups: The rats fed high fat-sucrose diet (506.8 kcal/100 g, lard, 10 g/100 g; cholesterol, 2 g/100 g; egg yolk power, 5 g/100 g; sucrose, 10 g/100 g; propylthiouracil, 2 g/100 g; basal diet, 72.8 g/100 g) and sacrificed at 20 days (M20) and at 30 days (M30), tryptophan (TRP)-free diet groups: The rats fed high fat-sucrose diet without tryptophan, and sacrificed at 20 days (R20) and at 30 days (R30), Tph1 inhibitor groups: The rats fed high fat-sucrose diet with LP533401 treatment (LP533401:17.5 mg•kg -1 •day -1 by gavage, Dalton Pharma Services, Toronto, Ontario, Canada), and sacrificed at 20 days (T20: treated with LP533401 from day 0 to day 20) and at 30 days (T30: treated with LP533401 from day 20 to day 30). All feed was provided by Trophic Animal Feed High-tech Co. Ltd (Nantong, China) (Wang et al, 2017). On days 20 and 30, the rats were killed by pentobarbital sodium (Merck, Germany) anesthesia following a 12 h fast in accordance with the experimental protocols.…”

Treinamento físico aeróbio e prevenção da doença hepática gordurosa não alcoólica: papel da lipogênese e do estresse de retículo no fígado

“…Isso porque é amplamente sabido que o aumento da massa adiposa e do peso corporal estão relacionadas com o desenvolvimento de resistência à insulina, DM2, hipertensão arterial e doença cardiovascular. Além disso, a obesidade pode levar ao acúmulo intracelular de lipídios e a formação de gotículas lipídicas nos hepatócitos, as quais podem ativar macrófagos e promover aumento das citocinas pró-inflamatórias, incluindo a IL-6 e o TNF-α, desempenhando papel significativo no desenvolvimento da DHGNA (WANG et al, 2017). Essa inflamação está associada à progressão da DHGNA à fibrose, cirrose e doença hepática crônica (RAHMAN et al, 2016).…”