Differential expression of glycoprotein IV on monocyte subsets following high-fat diet feeding and the impact of short-term low-dose aspirin treatment

Abstract

Objective: To assess the levels of glycoprotein GPIV (CD36) expression on peripheral blood monocyte subsets, in a mouse model of glucose intolerance. Moreover, to determine the effect of; low-dose aspirin (LDA) alone, LDA combined with metformin, or clopidogrel alone, on the expression of CD36 on subsets of circulating monocytes. Method: The study consisted of two experimental phases. In experiment one, the mice (n = 14) were randomised to receive a low-fat diet (LFD) or a high-fat diet (HFD) for eight weeks. Whereas the secondary phase of the experiment, comprised of twenty-four HFD-fed mice treated with LDA alone (3 mg/kg), or in combination with metformin (150 mg/kg), or clopidogrel alone (10 mg/kg) for six weeks. The surface expression of CD36 on monocytes was measured using flow cytometry. Result: The levels of CD36 expression on monocytes were upregulated in the HFD-fed compared to LFD-fed group (p < 0.05). In addition, HFD group showed; no significant changes in body weight (p = 0.3848), however, blood glucose (p = 0.0002) and insulin (p = 0.0360) levels were markedly increased following HFD-feeding. Interestingly, all treatments reduced the expression of CD36 on monocytes, decreased fasting blood glucose levels (p = 0.0024) and increased circulating monocyte levels (p = 0.0217) when compared to the untreated HFD group. Moreover, treatment with LDA alone increased basophils levels (p = 0.0272), while when combined with metformin showed an improved effect in enhancing eosinophil levels (p = 0.0302). Conclusion: HFD-feeding increased the expression of CD36 on monocyte subsets. LDA as a monotherapy or combined with metformin was as effective as clopidogrel monotherapy, in downregulating the expression of CD36 on monocyte subsets. These treatments may be of relevance in preventing cardiovascular complications associated with impaired glucose tolerance.