Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets

Chen, Yinshuang; Wang, Weipeng; Morgan, Maria P.; Robson, Tracy; Annett, Stephanie

doi:10.3389/fendo.2023.1148934

Cited by 16 publications

(7 citation statements)

References 283 publications

(406 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Obesity is a prominent global health concern that directly impacts liver health, leading individuals with obesity to face a substantial risk of elevated tumorigenesis in the liver 13 , 21 . Obesity, arising from an aberrant metabolic milieu, leads to modifications in immune function, initially manifesting as a state of persistent low-grade systemic inflammation and, in some cases, progressing to immune dysfunction 23 , 24 .…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, the available evidence regarding the connection between obesity and HCC is limited and inconclusive, leaving the question of causality uncertain 13 , 21 . Investigating the causal links between obesity and HCC holds great significance in the understanding of predisposing factors for diseases and in informing clinical treatment decisions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms

Chen,

Ding,

Chen

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms

Chen,

Ding,

Chen

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Complex and multifactorial pathogenic mechanisms underlie the association between NAFLD and hepatocarcinoma. Hypoglycemia, insulin resistance, chronic inflammation, oxidative stress, and dysregulated lipid metabolism have all been linked to the development of hepatocarcinoma in patients with NAFLD (19). In addition, as cirrhosis is a well-established risk factor for liver cancer, its presence in patients with NAFLD substantially elevates the likelihood of developing hepatocarcinoma.…”

Section: Epidemiological Evidence Of the Associationmentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease and the Risk of Future Hepatocarcinoma

Scholten

2024

Sci Insights

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition characterized by excess fat accumulation in the liver in the absence of significant alcohol consumption. While NAFLD itself is generally considered benign, it can progress to more severe forms such as non-alcoholic steatohepatitis, which can ultimately lead to liver cirrhosis and hepatocarcinoma, a type of liver cancer. The risk of developing hepatocarcinoma in individuals with NAFLD is considerably higher than in the general population. Factors such as obesity, diabetes, insulin resistance, and inflammation contribute to the development and progression of NAFLD and its subsequent transformation into hepatocarcinoma. Regular monitoring, lifestyle modifications, and timely treatment of co-existing conditions are crucial in mitigating the risk of hepatocarcinoma among patients with NAFLD. Further research into the underlying mechanisms linking NAFLD to hepatocarcinoma is essential for developing effective preventive strategies and treatments for this increasingly prevalent condition.

show abstract

“…Furthermore, increased intestinal permeability, excessive growth of intestinal bacteria, and serum endotoxin are observed in MAFLD and HCC. In parallel, the induction of TLR-2 is caused by endotoxemia, which promotes the production of prostaglandin E through the activation of the cyclooxygenase-2 pathway, suppressing antitumor immunity, inhibiting the production of antitumor cytokines from cells liver immune systems, and, consequently, progressing HCC [222].…”

Section: Mafld and The Development Of Hepatocellular Carcinomamentioning

confidence: 99%

Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

De Cól,

de Lima,

Pompeu

et al. 2024

IJMS

View full text Add to dashboard Cite

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain–gut–liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.

show abstract

Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets

Cited by 16 publications

References 283 publications

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms

Non-Alcoholic Fatty Liver Disease and the Risk of Future Hepatocarcinoma

Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

Contact Info

Product

Resources

About