Abstract
Adiposity is associated with an increased risk of various types of carcinoma. One of the plausible mechanisms underlying the tumor-promoting role of obesity is an aberrant secretion of adipokines, a group of hormones secreted from adipose tissue, which have exhibited both oncogenic and tumor-suppressing properties in an adipokine type- and context-dependent manner. Increasing evidence has indicated that these adipose tissue-derived hormones differentially modulate cancer cell-specific metabolism. Some adipokines, such as leptin, resistin, and visfatin, which are overproduced in obesity and widely implicated in different stages of cancer, promote cellular glucose and lipid metabolism. Conversely, adiponectin, an adipokine possessing potent anti-tumor activities, is linked to a more favorable metabolic phenotype. Adipokines may also play a pivotal role under the reciprocal regulation of metabolic rewiring of cancer cells in tumor microenvironment. Given the fact that metabolic reprogramming is one of the major hallmarks of cancer, understanding the modulatory effects of adipokines on alterations in cancer cell metabolism would provide insight into the crosstalk between obesity, adipokines, and tumorigenesis. In this review, we summarize recent insights into putative roles of adipokines as mediators of cellular metabolic rewiring in obesity-associated tumors, which plays a crucial role in determining the fate of tumor cells.
Highlights
Compelling evidence delineates that individuals with obesity have a higher risk of multiple malignancies, including endometrial cancer, hepatocellular carcinoma, colorectal cancer, esophageal adenocarcinoma, ovarian, and breast cancer [1,2]
In prostate cancer cells cultured in hypoxia, a condition leading to impaired mitochondrial respiration, leptin stimulates mitochondrial biogenesis, stabilization of mitochondrial membrane potential, and elevated uncoupled respiration through HIF-1α-dependent upregulation of uncoupling protein 2 (UCP2) [62]
Mounting evidence has shown that adipokines, in particular leptin and adiponectin, modulate cancer cell-specific metabolism in a complicated manner
Summary
Compelling evidence delineates that individuals with obesity have a higher risk of multiple malignancies, including endometrial cancer, hepatocellular carcinoma, colorectal cancer, esophageal adenocarcinoma, ovarian, and breast cancer [1,2]. Extensive efforts have been devoted to unveiling the pathological connection between excess adiposity and cancer, the mechanisms by which obesity promotes these malignancies are not completely understood. It has become increasingly clear that metabolic pathways in cancer cells are profoundly rewired to adapt to perturbations in a harsh tumor microenvironment. Since these metabolic adaptations seem to be an indispensable requirement for survival and exponential proliferation of tumor cells, understanding how cancer metabolism is remodeled and identifying factors, that drive metabolic remodeling, might open up new therapeutic opportunities [11]. Regulation of cancer cell metabolism by adipokines originating from distal adipose tissues can be mediated through an endocrinal mechanism [4]. We summarize the modulatory effects of adipokines on cancer cell-specific metabolism and highlight the crosstalk between other oncogenic signaling pathways and metabolic alterations driven by adipokines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
