Effect of Macronutrient Intake on Sirtuin 1 and 7 Expression in Mononuclear Cells of Normal Subjects

Presentation Number: SUN 257
Date of Presentation: April 2nd, 2017

Abdalmalik Bin Khunayfir*1, Mohammed Alrayih1, Hasan Alsayed1, Abdullah Alsadoon1, Mahmoud Zahra1, Maha Al Zayer2, Salman AlOtieschan1, Mohammed Saleh Al Dubayee2, 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

Abstract

Introduction:

Caloric restriction increases life expectancy in yeast, C. elegans and drosophila which has been shown to be mediated by the silence information regulator-2 (Sir-2). Members of Sir2 gene family consists of seven mammalian sirtuins (SIRT1-7). In mammals, their function is still largely unknown. SIRT1 has been the most studied mainly. Unexpectedly, SIRT1 expression in mononuclear cells (MNCs) has been shown to be increased in human obesity and to decrease following caloric restriction and weight loss. SIRT7, on the other hand, is associated with active rRNA genes (rDNA) and histones and increases RNA polymerase I (Pol I)-mediated transcription. SIRT7 is associated with resistance to stress and it was found to play a protective role and may even have anti-aging functions. In this study, we hypothesized that SIRT1 expression in MNCs increases while SIRT7 expression decreases following macronutrient intake.

Methods:

Thirty-six healthy subjects (Age: 21.4 ± 1.1 years; BMI: 22 ± 1.8 kg/m2) were randomly assigned into three groups (n=12 per group). 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 after or before caloric intake. Blood samples were collected at 0, 1, 2 and 3 hours following caloric or water intake. MNCs were isolated by Ficoll-Hypaque density gradient separation. SIRT1 and SIRT7 mRNA expressions by MNCs 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 mRNA was also quantitated in MNCs by RT-qPCR as a marker for monocyte differentiation into macrophages to examine any correlation with SIRT1 and SIRT7 expression.

Results:

Glucose, lipid and protein intake (300 kcal) all induced SIRT1 mRNA expression in MNCs. This increase was significant (P<0.05) only at 2 hrs (21.7 ± 9.5 fold) and 3 hrs (65.1± 37.3) following glucose intake. Lipid intake increased SIRT1 mRNA expression significantly at 1 hr (8.3 ± 10.3 fold), 2 hrs (13.4 ± 6.8 fold), and 3 hrs (17.0 ± 9.3 fold). Similarly, protein intake induced SIRT1 mRNA expression significantly at 1hr (10.3 ± 6.1 fold), 2 hrs (20.3 ± 7.1 fold), and 3 hrs (54.0 ± 27.2 fold). SIRT7 mRNA expression, on the other hand, did not change following macronutrient intake of 300 kcal. Equicaloric intake of either lipid or Whey protein resulted in macrophage differentiation as demonstrated by the increased expression of CD11b pan-macrophage marker at 1, 2 and 3 hrs. Glucose intake did not change CD11b mRNA expression by MNC.

Conclusions:

SIRT1 in humans is influenced by macronutrient intake. Macronutrient intake increases SIRT1 expression in MNCs in circulation. The role in the regulation of aging processes requires further elucidation. Additionally, SIRT7 expression is not influenced by macronutrients intake.

 

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