Abstract
Obesity-derived disturbances in fatty acid and cholesterol metabolism are linked to numerous diseases, including various types of malignancy. In tumor cells, metabolic alterations have been long recognized and intensively studied. However, metabolic changes in host cells in the tumor microenvironment and their contribution to tumor development have been largely overlooked. During the last decade, research advances show that fatty acid oxidation, cholesterol metabolism, and lipid accumulation play critical roles in cancer-associated host cells such as endothelial cells, lymph endothelial cells, cancer-associated fibroblasts, tumor-associated myeloid cells, and tumor-associated lymphocytes. In addition to anti-angiogenic therapies and immunotherapy that have been practiced in the clinic, metabolic regulation is considered another promising cancer therapy targeting non-tumor host cells. Understanding the obesity-associated metabolism changes in cancer-associated host cells may ultimately be translated into therapeutic options that benefit cancer patients. In this mini-review, we briefly summarize the lipid metabolism associated with obesity and its role in host cells in the tumor microenvironment. We also discuss the current understanding of the molecular pathways involved and future perspectives to benefit from this metabolic complexity.
Highlights
The global obesity pandemic affects most high-income and middle-income countries, and it is associated with an increased incidence of certain types of cancer (Swinburn et al, 2011; Demark-Wahnefried et al, 2012)
It is reported that obesityrelated hormone leptin promotes fatty acid oxidation (FAO) in endothelial cells (EC) by increasing CPT1α activity, suggesting obesity provides the fuel and is capable of triggering host cell metabolism (Yamagishi et al, 2001)
fatty acid synthase (FASN) upregulation in tumor-associated myeloid cells stimulates PPARβ/δ and supports tumor cell invasion (Park et al, 2015). In support of this view, various lipolytic enzymes involved in intracellular lipid metabolism, including monoacylglycerol lipase, AB-hydrolase containing 5, epidermal fatty acid-binding protein, and adipocyte/macrophage fatty acid-binding protein, strongly affect tumor-associated macrophages (TAMs) function and tumor progression (Rao et al, 2015; Miao et al, 2016; Hao et al, 2018; Xiang et al, 2018)
Summary
The global obesity pandemic affects most high-income and middle-income countries, and it is associated with an increased incidence of certain types of cancer (Swinburn et al, 2011; Demark-Wahnefried et al, 2012). There are still challenges to be faced in understanding how host cell lipid metabolism facilitates tumor development and in bringing the drugs that target cancer-associated host cell metabolism to the clinic. It is reported that obesityrelated hormone leptin promotes FAO in ECs by increasing CPT1α activity, suggesting obesity provides the fuel and is capable of triggering host cell metabolism (Yamagishi et al, 2001).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
