Involvement of the Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease
Abstract
1. Introduction
2. How High Fat/High Carbohydrate Consumption Induces NAFLD
Diet | Duration | Hepatic Steatosis | Hepatic Injury | Inflammation | Fibrosis | References |
---|---|---|---|---|---|---|
High fat (30–60% kcal) | 1–30 weeks | Bioassay TG content ↑ Histological steatosis ↑ | Serum ALT or AST ↑ Apoptotic markers ↑ Hepatocyte ballooning ↑ or none | Inflammatory markers ↑ No Histological inflammation | No change in fibrotic markers No histological fibrosis | [9,17,18,32,33] |
30–60 weeks | Bioassay TG content ↑ Histological steatosis ↑ | Serum ALT or AST ↑ Apoptotic markers ↑ Hepatocyte ballooning ↑ | Inflammatory markers ↑ Histological inflammation ↑ or none | Fibrotic markers ↑ Histological fibrosis ↑ | [15,16,32] | |
High fructose (20–60% fructose) | Up to 25 weeks | Bioassay TG content ↑ Histological steatosis ↑ | Serum ALT or AST ↑ Apoptotic markers ↑ Hepatocyte ballooning ↑ | Inflammatory markers ↑ Histological inflammation ↑ | No change in fibrotic markers No histological fibrosis | [7,10,13,14,33] |
High fat, high fructose | 12–25 weeks | Bioassay TG content ↑ Histological steatosis ↑ | Serum ALT or AST ↑ Apoptotic markers ↑ Hepatocyte ballooning ↑ | Inflammatory markers ↑ Histological inflammation ↑ | Fibrotic markers ↑ Histological fibrosis ↑ | [13,18,32,33,34,35] |
High fat, high cholesterol (0.2–2% cholesterol) | 12–42 weeks | Bioassay TG content ↑ Histological steatosis ↑ | Serum ALT or AST ↑ Apoptotic markers ↑ Hepatocyte ballooning ↑ | Inflammatory markers ↑ Histological inflammation ↑ | Fibrotic markers ↑ Histological fibrosis ↑ or none | [19,20,21,22] |
High fat, high fructose, high cholesterol | 25–30 weeks | Bioassay TG content ↑ Histological steatosis ↑ | Serum ALT or AST ↑ Apoptotic markers ↑ Hepatocyte ballooning ↑ | Inflammatory markers ↑ Histological inflammation ↑ | Fibrotic markers ↑ Histological fibrosis ↑ | [13,32,34,36] |
3. ER Stress and Its Possible Roles in the Pathogenesis of NAFLD
3.1. Involvement of ER Stress in the Development of Hepatic Steatosis
3.2. Involvement of ER Stress in the Progression to NASH
Signalling Pathways | Molecular Mechanisms | Biological Effects | References | |
---|---|---|---|---|
UPR pathways (activation) | IRE1/XBP1 | ↑ SREBP1c, ↑ ACC, ↑ FAS, ↑ SCD1 | ↑ lipogenesis | [31,37,38,39] |
↑ IKK, ↑ NF-κB, ↑ JNK ↑ NLRP3 | ↑ inflammation | [29,45] [46] | ||
↑ CHOP | ↑ apoptosis | [46] | ||
PERK/eIF2α | ↑ SREBP1c, ↑ ACC, ↑ FAS, ↑ SCD1 | ↑ lipogenesis | [7,9,31] | |
↑ IKK ↓ IκB, ↑ NFκB | ↑ inflammation | [29] [46] | ||
↑ CHOP, ↓ Bcl2 | ↑ apoptosis | [47] | ||
↑ ATF4, ↑ CHOP | ↓ autophagy | [48] | ||
ATF6 | ↑ PPARα, ↑ CPT1, ↑ ACOX-1 | ↑ fatty acid β-oxidation | [41,42] | |
↓ SREBP2 | ↓ lipogenesis | [43] | ||
↑ SREBP1c, ↑ ACC, ↑ FAS, ↑ SCD1 | ↑ fatty acid synthesis | [7,49] | ||
Autophagy (inhibition) | ↓ Atg7 | ↑ ER stress ↓ fibrosis | [7,50] [30] | |
↑ TNFα, ↑ IL-6 ↑ TLR4 ↑ NLRP3, ↑ IL-1β ↑ NF-κB | ↑ inflammation | [51,52] [52] [52,53,54] [52] |
4. Autophagy and Its Possible Role in the Pathogenesis of NAFLD
5. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Zhou, X.; Fouda, S.; Li, D.; Zhang, K.; Ye, J.-M. Involvement of the Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease. Nutrients 2020, 12, 2626. https://doi.org/10.3390/nu12092626
Zhou X, Fouda S, Li D, Zhang K, Ye J-M. Involvement of the Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease. Nutrients. 2020; 12(9):2626. https://doi.org/10.3390/nu12092626
Chicago/Turabian StyleZhou, Xiu, Sherouk Fouda, Dongli Li, Kun Zhang, and Ji-Ming Ye. 2020. "Involvement of the Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease" Nutrients 12, no. 9: 2626. https://doi.org/10.3390/nu12092626
APA StyleZhou, X., Fouda, S., Li, D., Zhang, K., & Ye, J.-M. (2020). Involvement of the Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease. Nutrients, 12(9), 2626. https://doi.org/10.3390/nu12092626