Monocyte Differentiation and Macrophage Polarization in Circulation in Response to Macronutrient Intake in Healthy Humans

Presentation Number: SUN 258
Date of Presentation: April 2nd, 2017

Hasan Alsayed*1, Abdalmalik Bin Khunayfir1, Mohammed Alrayih1, Abdullah Alsadoon1, Mahmoud Zahra1, Yousof Alrumayyan1, Maha Al Zayer2, Mohammed Saleh Al Dubayee2, Amre Nasr3, Ahmad Aljada3 and Awad Saad Alshahrani2
1King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia, 2National Guard Health Affairs, Riyadh, Saudi Arabia, 3KSAU-HS, Riyadh, Saudi Arabia



Macrophages can exhibit distinct phenotypes and functions in response to inflammatory stimuli and can polarize into one of two distinct phenotypes, a pro-inflammatory (M1) macrophage phenotype and an anti-inflammatory pro-tissue (M2) macrophage phenotype. It is difficult to dissect macrophage phenotypes in vivo or in vitro following stimulation, e.g. IFNγ or IL-4. Glucose and lipid intakes have been demonstrated to exert pro-inflammatory effects on mononuclear cells (MNCs) of healthy subjects. They activated NFkB, Egr-1, AP-1, TF, and MCP-1, while casein protein intake did not activate these pathways. In this study, we examined in vivo macrophage differentiation into different macrophage phenotypes following equicaloric intake of macronutrients (glucose, protein, and lipid) in healthy subjects.


Thirty-six healthy volunteers (Age: 21.4 ± 1.1 years, BMI: 22 ± 1.8 kg/m2) were recruited in the study. They were randomly assigned into three groups, each group consisting of 12 participants. Each group drank equal calories (300 kcal) of either glucose or lipid (cream) or whey protein. Each subject served as his own control by drinking 75 mL of water 1 week before or after the caloric intake. Baseline blood samples were drawn before the caloric or water intake, and subsequent blood samples were drawn at 1, 2 and 3 hours post caloric or water intake. MNCs were isolated, and macrophage polarization markers (M1: CD86, IL-6, CD11c, and CD169, and M2: CD68, CD163, and CD36) were measured by reverse transcription quantitative real time PCR (RT-qPCR). Gene expression fold change was calculated using the 2ˆ(–delta delta Ct) method for RT-qPCR. CD11b was used as a marker for pan macrophages.


Equicaloric intake of either glucose, lipid, or whey protein resulted in distinct macrophage phenotypes as demonstrated by the differential expression of macrophage differentiation markers. Whey protein intake resulted in significant mRNA upregulation in MNCs of CD68 and CD11b at 1, 2, and 3 hrs post intake (P<0.05) while mRNA of IL-6 was significantly inhibited at 1 hr. Lipid intake resulted in mRNA upregulation of CD11b at 2 and 3 hrs (P<0.05). There were no significant changes in the other macrophage differentiation markers (CD86, CD163, CD169, CD11c, and CD36) following either whey protein or lipid intakes. Glucose intake did not induce mRNA expression of any marker measured.


Whey protein induces M2 macrophage phenotype as demonstrated by increased CD68, CD11b, and inhibition of IL-6 mRNA expression. Lipid induces monocyte differentiation into macrophages as indicated by the increase in CD11b. Finally, lack of CD11b increase and the other markers tested following glucose intake suggests lack of monocyte differentiation to macrophages following glucose intake. In conclusion, only whey protein intake induces macrophage polarization into one of its two phenotypes.


Nothing to Disclose: HA, AB, MA, AA, MZ, YA, MA, MSA, AN, AA, ASA