We identify a critical role of increased oxidation of fatty acids driven by leptin and PD-1 through STAT3 in inhibiting CD8<sup>+</sup> T effector cell glycolysis and in promoting obesity-associated breast tumorigenesis.
Accumulating evidence has shown gastric leptin to perform diverse functions, such as those in nutrient absorption and carcinogenesis in the gastrointestinal system, independent of its well-known role in appetite regulation and obesity.
Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models.
This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).
In addition, an interesting result was found that the impact of LEP-2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption.
<b>Background:</b> Leptin (LEP) is a human analogous form of the mouse obese gene and plays a critical role in energy expenditure as well as the progression of carcinogenesis.
Our findings suggest that leptin impairs responsivity of OSCC cells to the ionizing radiation, reducing the suppressive effects of irradiation on the neoplastic phenotype, and increasing protein expression critical to carcinogenesis.
Leptin stimulated migration and invasion of cultured HCT-116 cells and tumor growth in the xenograft assay, and these effects were abrogated by a SIRT1 inhibitor sirtinol, suggesting that SIRT1 plays a role in leptin-induced colon carcinogenesis.
While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis.
Leptin plays an important role in carcinogenesis as leptin/leptin receptor signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell apoptosis.
This study therefore determines if chronic leptin administration induces gastric carcinogenesis in non-obese rats, which might serve as a useful animal model for future studies.
Recently, low-serum level of 25-hydroxy vitamin D (25(OH)D) and obesity have been suggested to increase the BC risk, and leptin, which is important in weight regulation, may be involved in bladder carcinogenesis.
It is evident from various studies that leptin, a 16 kDa protein hormone overproduced in obese people, plays the critical role in neovascularization and tumorigenesis in breast and other organs.
Therefore, we hypothesize that over-expression of LEPR, rather than that of LEP has a fundamental role in breast carcinogenesis in particular, and probably for LEP-LEPR associated tumors in general.
Obesity is linked with an increased cancer risk and studies have also revealed that leptin may be involved in breast tumorigenesis particularly among obese women.