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Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer.

ABSTRACT: Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

SUBMITTER: Gyamfi J

PROVIDER: S-EPMC8463699 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Adipocyte fatty acid binding protein (FABP4) has been recently characterized as an adipokine that is closely associated with obesity and metabolic syndrome. Irisin, a novel myokine, activates thermogenesis by increasing the transformation of white adipocytes to brown, and it has improved glucose homeostasis in animal models. In this study, we aimed to explore the relationship between serum FABP4 and irisin in middle-aged Chinese subjects.A total of 111 normal residents (56 men and 55 women) of Fengxian District who were 40 to 60 years of age were recruited. Circulating FABP4 and irisin were determined by enzyme-linked immunosorbent assay. Anthropometric parameters, oral glucose tolerance test results, hemoglobin A1C (HbA1C), blood lipids, homeostasis model assessment of insulin resistance, homeostasis model assessment-β and body fat composition were also determined.All participants were categorized by FABP4 tertiles. There were significant differences in blood pressure, body fat percentage, 2-h plasma glucose, and skeletal muscle mass among the three groups (P<0.05). Furthermore, FABP4 levels in the women were significantly higher than in the men (P<0.05). However, there was no sexual dimorphism in serum irisin (P>0.05). To exclude the effect of sex difference, partial correlations analysis showed that FABP4 was positively correlated with diastolic blood pressure (P<0.05) and body fat percentage (P<0.05) negatively correlated with skeletal muscle mass (P<0.05) and irisin (P<0.05), while irisin was positively correlated with HbA1c (P<0.05) and negatively correlated with creatinine (P<0.05). Multivariate regression analysis demonstrated that serum FABP4 was independently associated with skeletal muscle mass (P<0.001), diastolic blood pressure (P<0.05) and irisin (P<0.05) after adjustment for age, body mass index, body fat percentage, total cholesterol and HbA1C.Elevated FABP4 levels increase the risks of obesity-related metabolic disorders and hypertension. Serum irisin might exert antagonistic effects on FABP4 in the middle-aged Chinese population.

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Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer.

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