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Review
. 2022 Apr 24;23(9):4713.
doi: 10.3390/ijms23094713.

Leptin Signaling in Obesity and Colorectal Cancer

Claudia Terezia Socol  1 , Alexandra Chira  2 , Maria Antonia Martinez-Sanchez  3 , Maria Angeles Nuñez-Sanchez  3 , Cristina Maria Maerescu  1 , Daniel Mierlita  4 , Alexandru Vasile Rusu  5   6 , Antonio Jose Ruiz-Alcaraz  7 , Monica Trif  8 , Bruno Ramos-Molina  3
Affiliations
Review

Leptin Signaling in Obesity and Colorectal Cancer

Claudia Terezia Socol et al. Int J Mol Sci. .

Abstract

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin's relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.

Keywords: LEP; LEPR; colorectal cancer; microbiome; obesity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Factors influencing obesity and CRC risk.
Figure 2
Figure 2
Leptin’s role in obesity and CRC.
Figure 3
Figure 3
LEP and LEPR gene expression levels in healthy and in various colorectal carcinoma tissues. Data were retrieved from the online IST database (https://ist.medisapiens.com/, accessed on 24 June 2021).
Figure 4
Figure 4
LEP and LEPR gene expression association with colorectal cancer phenotypes. Data represent the expression values of LEP (a) and LEPR (b) in colorectal cancer samples with several types of clinical data, within each cancer dataset. Each sample is represented by a single datapoint. Each type of clinical data exists as a column within a separate segment of the phenoplot. Expression values are also presented as red box plots. Boxes represent samples with distinct phenotypic values as black dots in the clinical data segments. A box is only shown if there are more than five distinct phenotypic values. Data were retrieved from the online IST database (https://ist.medisapiens.com/, accessed on 24 June 2021).
Figure 4
Figure 4
LEP and LEPR gene expression association with colorectal cancer phenotypes. Data represent the expression values of LEP (a) and LEPR (b) in colorectal cancer samples with several types of clinical data, within each cancer dataset. Each sample is represented by a single datapoint. Each type of clinical data exists as a column within a separate segment of the phenoplot. Expression values are also presented as red box plots. Boxes represent samples with distinct phenotypic values as black dots in the clinical data segments. A box is only shown if there are more than five distinct phenotypic values. Data were retrieved from the online IST database (https://ist.medisapiens.com/, accessed on 24 June 2021).
Figure 5
Figure 5
Effect of LEP mutations on leptin expression in obesity and CRC.
See this image and copyright information in PMC

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References

    1. World Health Organization Obesity and Overweight. [(accessed on 19 July 2021)]. Available online: http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
    1. Shabana, Ullah Shahid S., Wah Li K., Acharya J., Cooper J.A., Hasnain S., Humphries S.E. Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects. Eur. J. Hum. Genet. 2015;24:903–910. doi: 10.1038/ejhg.2015.212. - DOI - PMC - PubMed
    1. Soltani G., Poursheikhani A., Yassi M., Hayatbakhsh A., Kerachian M., Kerachian M.A. Obesity, diabetes and the risk of colorectal adenoma and cancer. BMC Endocr. Disord. 2019;19:113. doi: 10.1186/s12902-019-0444-6. - DOI - PMC - PubMed
    1. World Obesity Obesity Classification. [(accessed on 19 July 2021)]. Available online: https://www.worldobesity.org/about/about-obesity/obesity-classification.
    1. Forstner S., Rusu A. Development of personalised food for the nutrition of elderly consumers. In: Dumitras D.E., Jitea I.M., Aerts S., editors. Know Your Food. Food Ethics and Innovation. Wageningen Academic Publishers; Wageningen, The Netherlands: 2015. pp. 24–28.