PMID- 31920356 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220412 IS - 1178-7007 (Print) IS - 1178-7007 (Electronic) IS - 1178-7007 (Linking) VI - 12 DP - 2019 TI - Differential Expression of Human N-Alpha-Acetyltransferase 40 (hNAA40), Nicotinamide Phosphoribosyltransferase (NAMPT) and Sirtuin-1 (SIRT-1) Pathway in Obesity and T2DM: Modulation by Metformin and Macronutrient Intake. PG - 2765-2774 LID - 10.2147/DMSO.S228591 [doi] AB - BACKGROUND: Interactions between environmental factors, such as diet and lifestyle, and metabolic pathways are pivotal in understanding aging mechanisms. hNAA40, Nicotinamide phosphoribosyltransferase (NAMPT), and NAD-dependent protein deacetylase sirtuin-1 (SIRT-1) have been shown to exert important biological processes, including stress response and aging. METHODS: hNAA40, NAMPT, and SIRT-1 mRNA expression in peripheral blood mononuclear cells (PBMC) were quantitated in 30 lean adult volunteers of normal weight, 30 obese, 20 drug-naive obese Type 2 diabetes mellitus (T2DM), and 30 obese T2DM on Metformin. Similarly, hNAA40, NAMPT, and SIRT-1 expression in PBMC were quantitated in 36 normal healthy adults randomly assigned to three different groups (Glucose or Whey proteins or lipids; 300 kcal). Blood samples were obtained at 1, 2, and 3 hrs after the macronutrient intake. RESULTS: There was an increase in hNAA40 and a decrease in NAMPT and SIRT-1 expression in PBMC from T2DM. Metformin treatment reverted hNAA40, NAMPT, and SIRT-1 expression levels to normal levels. Glucose intake resulted in a significant increase in expression of hNAA40 at 1 hr and decreased significantly at 3 hrs post intake. Lipid intake resulted in an increase in expression of hNAA40 at 2 hr post intake and returned to normal levels at 3 hrs. Neither glucose nor lipid intake resulted in a significant change in NAMPT or SIRT-1 expression. Whey proteins resulted in significantly lower expression of NAMPT at 3 hrs and did not alter the expression levels of SIRT-1 significantly. CONCLUSION: hNAA40, NAMPT, and SIRT-1 pathway could play a role in the determination of the healthy life-span. Metformin modulates this pathway. CI - (c) 2019 Alshahrani et al. FAU - Alshahrani, Awad AU - Alshahrani A AD - Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Kingdom of Saudi Arabia. AD - King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Kingdom of Saudi Arabia. AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - AlDubayee, Mohammed AU - AlDubayee M AD - Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Kingdom of Saudi Arabia. AD - King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Kingdom of Saudi Arabia. AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - Zahra, Mahmoud AU - Zahra M AUID- ORCID: 0000-0001-5067-4984 AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - Alsebayel, Firas M AU - Alsebayel FM AUID- ORCID: 0000-0001-5053-7410 AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - Alammari, Nawaf AU - Alammari N AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - Alsudairy, Faisal AU - Alsudairy F AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - Almajed, Muath AU - Almajed M AD - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. FAU - Aljada, Ahmad AU - Aljada A AUID- ORCID: 0000-0001-8337-5454 AD - Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia. LA - eng PT - Journal Article DEP - 20191227 PL - New Zealand TA - Diabetes Metab Syndr Obes JT - Diabetes, metabolic syndrome and obesity : targets and therapy JID - 101515585 PMC - PMC6938199 OTO - NOTNLM OT - NAMPT OT - T2DM OT - hNAA40 OT - nicotinamide phosphoribosyltransferase OT - obesity OT - senescence OT - sirtuin-1 COIS- All authors declare no conflicts of interest in relation to the work reported in this manuscript. EDAT- 2020/01/11 06:00 MHDA- 2020/01/11 06:01 PMCR- 2019/12/27 CRDT- 2020/01/11 06:00 PHST- 2019/08/24 00:00 [received] PHST- 2019/11/27 00:00 [accepted] PHST- 2020/01/11 06:00 [entrez] PHST- 2020/01/11 06:00 [pubmed] PHST- 2020/01/11 06:01 [medline] PHST- 2019/12/27 00:00 [pmc-release] AID - 228591 [pii] AID - 10.2147/DMSO.S228591 [doi] PST - epublish SO - Diabetes Metab Syndr Obes. 2019 Dec 27;12:2765-2774. doi: 10.2147/DMSO.S228591. eCollection 2019.