Low expression of Elovl6 may involve in fat loss in white adipose tissue of cancer-associated cachexia

Background: Cancer-associated cachexia (CAC) arises from malignant tumors and leads to a debilitating wasting syndrome. In the pathophysiology of CAC, the depletion of fat performs a significant function. The mechanism of CAC-induced fat loss includes the enhancement of lipolysis, inhibition of lipogenesis, and browning of white adipose tissue (WAT), however, few lipid-metabolic enzymes have been reported to be involved in CAC. This study hypothesized that Elovl6, a critical enzyme for elongation of fatty acids, may involve in fat loss in CAC. Method: Transcriptome sequencing technology was employed to identify CAC-related genes in the WAT of a CAC rodent model. Then the expression level of Elovl6 and fatty acid composition were analyzed in a large clinical sample. Elovl6 was knocked down in 3T3-L1 mouse preadipocytes to compare with wild-type 3T3-L1 cells treated with tumor cell-conditioned medium. Result: In the WAT of patients with CAC, a significant decrease in the expression of Elovl6 was found, which correlates with the extent of body mass reduction in a linear relationship. Gas chromatographic analysis revealed an augmentation in palmitic acid (C16:0) and a reduction in linoleic acid (C18:2n6c) content in those tissue samples. Treating with tumor cell-conditioned medium, 3T3-L1 mouse preadipocytes showed a decrease of Elov16, and Elovl6-knockdown cells demonstrated reduced pre-adipocyte differentiation and lipogenesis. Likewise, the knockdown of Elovl6 in 3T3-L1 cells exhibited a significant rise in palmitic acid (C16:0) and a remarkable decrease in oleic acid (C18:1n9c) content. Conclusion: Overall, the expression of Elovl6 was diminished in the WAT of CAC patients. The decreased expression of Elovl6 might lead to fat loss in CAC by potentially altering the fatty acid composition in adipocytes. These findings suggest that Elovl6 may be used as a valuable biomarker for early diagnosis of CAC, and hold promise as a target for future therapies.