Longitudinal, Diet-induced Weight Gain is Associated with Increased Blood Monocytes and Reduced TLR4 Expression

Excessive weight gain increases systemic inflammation resulting in increased disease risk. Toll-like receptor 4 (TLR4) reportedly mediates increases in inflammation; however, its role in obesity-induced inflammation has not been fully evaluated. The purpose of this study was to determine the longitudinal effect of diet-induced weight gain on blood monocyte concentration and cell-surface TLR4 expression. Male CD-1 mice were randomly assigned to high-fat (HF, n = 12) or low-fat (LF, n = 13) groups. Non-lethal, saphenous vein blood samples were collected at 0, 4, 8 and 12 weeks of treatment. Three-color flow cytometry was used to measure monocyte (CD11b⁺/CD14⁺) concentration and TLR4 cell-surface expression. Data were analyzed with a repeated measures ANOVA; significance was set at P<0.05. Body weight at week 12 was 21% greater in HF than LF (P<0.05). At week 12 HF had 155% more monocytes (P<0.05) with 24% less TLR4 than LF; Monocyte concentration and body weight at week 12 was negatively correlated with TLR4 gMFI (P<0.05). The observed effects of high-fat feeding on blood monocytes are consistent with a phenotype, which may be associated with premature morbidity. The observed monocyte responses may be associated with immune dysfunction and diminished response to infection.