The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles

Moayedfard, Zahra; Sani, Farnaz; Alizadeh, Ali; Lankarani, Kamran Bagheri; Zarei, Mohammad; Azarpira, Negar

doi:10.1186/s13287-022-02929-6

Cited by 21 publications

(29 citation statements)

References 150 publications

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“…Moreover, multiple cytokines or chemokines secreted by immune cells and parenchymal cells are involved in the occurrence and development of NAFLD, such as the complement system. It is composed of complement main components, humoral regulatory factors, and complement receptors (6,7). The complement system is a highly regulatory protein reaction system, including more than 60 components, which are widely distributed in serum, tissue fluid and cell membrane surface.…”

Section: Introductionmentioning

confidence: 99%

“…Complement component 3 a (C3a) was associated with hepatic steatosis and hepatocellular injury in humans (20, 21). In addition, C5 promoted the deposition of liver triglycerides (TGs) to some extent and increased the occurrence of liver steatosis and inflammation (6,7). Compared with the lean control group, the serum complement component 5 a (C5a) concentration was higher in obese children with NAFLD (22).…”

Section: Introductionmentioning

confidence: 99%

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Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis

Zhao

et al. 2022

Front. Immunol.

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BackgroundIt is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a variety of complement components, and the relationship between complement components and the risk and severity of NAFLD is inconsistent. The aim of this meta-analysis was to evaluate the association of complement components with the risk and severity of NAFLD.MethodsWe searched PubMed, Embase, Cochrane Library, Google Scholar, Scopus, and ZhiWang Chinese databases from inception to May 2022 for observational studies reporting the risk of NAFLD with complement components. Random-effects meta-analysis was used to obtain pooled estimates of the effect due to heterogeneity.ResultsWe identified 18 studies with a total of 18560 included subjects. According to recent studies, levels of complement component 3 (C3) (mean difference (MD): 0.43, 95% confidence interval (CI) 0.26-0.60), complement component 4 (C4) (MD: 0.04, 95% CI 0.02-0.07), complement component 5(C5) (MD: 34.03, 95% CI 30.80-37.27), complement factor B (CFB) (MD: 0.22, 95% CI 0.13-0.31) and acylation stimulating protein (ASP) (standard mean difference (SMD): 5.17, 95% CI 2.57-7.77) in patients with NAFLD were significantly higher than those in the control group. However, no statistical significance was obtained in complement factor D (CFD) levels between NAFLD and non-NAFLD (MD=156.51, 95% CI -59.38-372.40). Moreover, the levels of C3, C5, CFB, and ASP in patients with moderate and severe NAFLD were significantly higher than those in patients with mild NAFLD. Except for C4 and CFD, the included studies did not explore the changes in the severity of NAFLD according to the concentration of C4 and CFD.ConclusionsThis meta-analysis demonstrates that an increase in complement components including C3, C5, CFB, and ASP is associated with an increased risk and severity of NAFLD, indicating that they may be good biomarkers and targets for the diagnosis and treatment of NAFLD.Systematic review registrationPROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42022348650.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis

Zhao

et al. 2022

Front. Immunol.

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“…Usually, procedures that involve exogenous MSCs injections examine only a limited number of variables before concluding that the exogenous MSCs have a vital role in the repair of NAFLD. [52][53][54] VAT, BMI, and cortisol significantly decreased accompanied by an optimal statistically significant increase in testosterone, BMR and skeletal muscle mass. This additional data suggested an overall health improvement and enhanced fitness.…”

Section: Discussionmentioning

confidence: 92%

Liver repair of NAFLD patients following effortless exercise and the possible involvement of endogenous stem cells

Sofra¹

2022

JDMDC

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Adipose tissue derived stem cells differentiate into mesenchymal stem cells (MSCs) and hepatocytes which are involved in anti-inflammatory, reparatory, and detoxification processes reinstating liver function. Aerobic, resistance and effortless workouts have been proven to be beneficial for patients with NAFLD, possibly due to stem cells released into the bloodstream from metabolized fat during exercise induced natural lipolysis. We analysed the serum levels of a number of variables such as ALT, AST, ALP, albumin, creatinine, bilirubin, triglycerides and CRP to determine if effortless exercise would demonstrate an improvement of the NAFLD condition that is substantially equivalent to liver repair documented after administering exogenous MSCs injections. We examined 10 prediabetic individuals with NAFLD, 5 males and 5 females 54-64 years of age, who received 15 treatments with an effortless exercise technology, originally invented at London University for obese individuals who have difficulty performing strenuous workouts, as well as those with limited mobility due to age or disease. The hypothesis was that the reduction of triglycerides and visceral adipose tissue (VAT) is accompanied by a natural release of adipose tissue contents into the bloodstream, supplying endogenous MSCs that differentiate into hepatocytes necessary for healthy liver functioning. Results demonstrated a statistically significant improvement of the NAFLD condition in ultrasonography reports along with optimal levels of ALT, AST, ALP, albumin, creatinine, bilirubin and CRP. Additional findings included a notable decrease in triglycerides, VLDL, BMI, VAT, and cortisol, accompanied by an increase in testosterone, BMR, and muscle mass. Our results replicated previous studies which documented a significant repair of hepatic steatosis in ultrasonography reports after using this effortless exercise regimen. The current clinical study strongly suggested the involvement of endogenous MSCs that are vital in organ repair. Reducing VLDL, VAT and triglycerides optimizes health, setting the conditions for the reparative process to commence. The possibility of endogenously released MSCs as a result of an exercise method is a new perspective with very little past research, therefore, more clinical studies focusing on this hypothesis are warranted. Demonstrating the production of endogenous MSCs via an exercise modality will introduce novel treatments for metabolic disorders without the adverse effects often observed after stem cells injections or invasive and trauma based procedures.

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“…179 Under certain conditions, such as inhibition of key enzymes involved in TG formation, dysfunction of β-oxidized fatty acids, and lipolysis of adipose tissue in IR, excess SFAs can be generated to result in lipotoxic intermediates. 180 Accumulation of TG leads to toxic metabolites that cause endoplasmic reticulum stress, accumulation of misfolded proteins, and formation of ROS, ultimately leading to apoptosis, a major factor in the pathogenesis of NASH. 181 As a key transcription factor of the antioxidant defense system, NRF2 can initiate the transcription of a series of cytoprotective genes, such as HO-1 and NQO-1.…”

Section: The Regulatory Mechanism Of Tea Active Compounds On Nafldmentioning

confidence: 99%

Regulatory Effects and Molecular Mechanisms of Tea and Its Active Compounds on Nonalcoholic Fatty Liver Disease

Yang

Huang

et al. 2023

J. Agric. Food Chem.

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Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is a multifactorial disease resulting from the interaction between environment, genetic background, and metabolic stress. Most treatments for NAFLD include dietary intervention and exercise show limited efficacy due to the complex mechanisms involved in NAFLD. Meanwhile, drug therapy is accompanied by serious side effects. The development of high-efficiency natural supplements is a sustainable strategy for the prevention and treatment of NAFLD. As the second most consumed beverage, tea has health benefits that have been widely recognized. Nevertheless, the intervention of tea active compounds in NAFLD has received limited attention. Tea contains abundant bioactive compounds with potential effects on NAFLD, such as catechins, flavonoids, theanine, tea pigments, and tea polysaccharides. We reviewed the intrinsic and environmental factors and pathogenic mechanisms that affect the occurrence and development of NAFLD, and summarized the influences of exercise, drugs, diet, and tea drinking on NAFLD. On this basis, we further analyzed the potential effects and molecular regulatory mechanisms of tea active compounds on NAFLD and proposed future development directions. This review hopes to provide novel insights into the development and application of tea active compounds in the prevention and treatment of NAFLD.

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The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles

Cited by 21 publications

References 150 publications

Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis

Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis

Liver repair of NAFLD patients following effortless exercise and the possible involvement of endogenous stem cells

Regulatory Effects and Molecular Mechanisms of Tea and Its Active Compounds on Nonalcoholic Fatty Liver Disease

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