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Review
. 2019 Jan 1;15(3):610-616.
doi: 10.7150/ijbs.29599. eCollection 2019.

Obesity, Nonalcoholic Fatty Liver Disease and Adipocytokines Network in Promotion of Cancer

Rosa Divella  1 , Antonio Mazzocca  2 , Antonella Daniele  1 , Carlo Sabbà  2 , Angelo Paradiso  3
Affiliations
Review

Obesity, Nonalcoholic Fatty Liver Disease and Adipocytokines Network in Promotion of Cancer

Rosa Divella et al. Int J Biol Sci. .

Abstract

Western populations are becoming increasingly sedentary and the incidence of nonalcoholic fatty liver disease (NAFLD) is increasing and becoming one of the most common causes of liver disease worldwide. Also, NAFLD is considered one the new emerging risk factors for development of tumors of the gastro-intestinal tract, particularly hepatocellular carcinoma (HCC). Visceral obesity is an important risk factor for the onset of NAFLD. An accumulation of ectopic fat, including visceral obesity and fatty liver leads to a dysfunction of the adipose tissue with impaired production of adipocytokines which, in turn, favor an increase in pro-inflammatory cytokines. In this review, we discuss how the obesity-related chronic state of low-grade inflammation and the presence of NAFLD lead to the emergence of a microenvironment favorable to the development of cancer.

Keywords: NAFLD; adipocytokines; cancer; inflammation; obesity.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Relationship between metabolic syndrome, NAFLD, and development of colorectal adenoma and carcinoma.
Figure 2
Figure 2
The pathogenesis of NAFLD. Peripheral insulin resistance (IR) promotes increased production of free fatty acids (FFA) direct in the liver, resulting in an imbalance between oxidation/divestiture and uptake/synthesis of FFA, and then steatosis liver. The fabric fat secretes adipokines such as leptin, able to adjust the adipocyte metabolism and numerous insulin-mediated processes. Adiponectin plays a role in anti-inflammatory and anti-steatotic; its secretion It is in part regulated by TNF-α under the control of NF-kB.
Figure 3
Figure 3
The state of chronic low-grade inflammation due to obesity and the presence of NAFLD leads to the emergence of a micro-environment favorable to the development of cancer and the onset of insulin resistance due to activation of the axis that regulates the insulin growth factor-1 IGF-1 and insulin resulting in hyperinsulinemia. Through its proliferative and anti-apoptotic effects, this process can increase mutations that promote carcinogenesis.
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