Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 22;22(4):2163.
doi: 10.3390/ijms22042163.

Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer

Yetirajam Rajesh  1 , Devanand Sarkar  2
Affiliations
Review

Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer

Yetirajam Rajesh et al. Int J Mol Sci. .

Abstract

Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC.

Keywords: HCC; NAFLD/NASH; adipokines; adiponectin; adipose tissue; leptin; therapeutic targets.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanism involved in normal healthy adipocytes. In response to a sedentary lifestyle, food intake, and an increase in circulating insulin, small healthy adipocytes absorb different types of lipids. They tend to suppress lipogenesis and secrete adiponectin (ADP). ADP promotes insulin sensitivity and fatty acid (FA) oxidation. During fasting, triglyceride lipases (TGLs) become activated, releasing free fatty acids (FFAs). Blue upward arrow indicates an increase.
Figure 2
Figure 2
Correlation between adipose tissue and adipokines with the development of obesity-induced hepatocellular carcinoma (HCC) and the effect of adiponectin agonists and other inhibitors. The adipose tissue (AT) secretes various bioactive peptides, known as adipokines, and their associated dysregulation has been implicated in metabolic disorders caused by obesity. The swollen and dedifferentiated adipocytes secrete less adiponectin (ADP) during obesity, and ADP is the only adipokine of which the circulating levels are significantly reduced during obesity. In muscles and the liver, ADP increases insulin action and exerts an antiatherogenic effect. Leptin is another adipokine that regulates energy balance and exerts an insulin-sensitizing effect, but its beneficial effects are reduced in obesity due to leptin resistance. In obese individuals, an inflammatory state is contributed through macrophage infiltration due to excessive production of TNFα, IL-6, or resistin deteriorating insulin action in the liver. Increased lipolysis secretes FAs that accumulate triglyceride in visceral adipose tissue (VAT) in correlation with insulin resistance (IR). The IR and elevated FFAs predispose to steatosis, promoting hepatic lipogenesis and increasing SREBP1 and ChREBP1 expression, further promoting damage to liver tissues and a state of inflammatory response, resulting in NASH followed by HCC. The inflammatory response promoted by obese AT contributes to damage of hepatic cells and impaired immune response. The administration of ADP agonists and AT targeting inhibitors might be a promising therapeutic target for adipokine-mediated obesity-induced HCC. Blue upward arrow indicates an increase and blue downward arrow indicates a decrease.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rajesh Y., Sarkar D. Molecular Mechanisms Regulating Obesity-Associated Hepatocellular Carcinoma. Cancers. 2020;12:1290. doi: 10.3390/cancers12051290. - DOI - PMC - PubMed
    1. Sun B., Karin M. Obesity, inflammation, and liver cancer. J. Hepatol. 2012;56:704–713. doi: 10.1016/j.jhep.2011.09.020. - DOI - PMC - PubMed
    1. Kershaw E.E., Flier J.S. Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 2004;89:2548–2556. doi: 10.1210/jc.2004-0395. - DOI - PubMed
    1. Ronti T., Lupattelli G., Mannarino E. The endocrine function of adipose tissue: An update. Clin. Endocrinol. 2006;64:355–365. doi: 10.1111/j.1365-2265.2006.02474.x. - DOI - PubMed
    1. Jung U.J., Choi M.S. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci. 2014;15:6184–6223. doi: 10.3390/ijms15046184. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources