<p>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</p>

Abstract

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 drugnaïve 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 lifespan. Metformin modulates this pathway.

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone

“…In our study, SIRT1 levels of Wistar proved to be unusually low, even seemingly lower than that of Goto control group, although the difference did not reach the level of statistical significance. According to other scientific articles, calorie restriction increases SIRT1 concentrations [38] while in contrast overweight and obesity is associated with SIRT1 down-regulation [39,40], which might have been the reason in our experiment for the lower than usual SIRT1 expression in case of the Wistar rats that produced significant weight gain during the study.…”

NAMPT, IL-6, and vaspin gene expressions and serum protein levels in type 2 diabetes mellitus and related complication

“…The results of the present study indicate that NAMPT serum levels decrease considerably in the group without complications compared to all other groups and controls. Similarly, Alshahrani et al (2019) stated that NAMPT expression is reduced in obese patients with T2DM, and metformin treatment reverts NAMPT expression to normal levels. However, Kieswich et al (2016) showed that serum levels increased for monomeric eNAMPT in diabetic mice.…”

Inter‐Individual Variation in Postprandial Glycemic Responses in Women Co‐Ingesting Green Leafy Vegetables with a Carbohydrate Meal: Interactions with the Sirtuin System

“…PCA analysis indicated sirtuin system gene expression patterns were not ascribed by menopausal status or the meal consumed except for reduced NAMPT in post‐menopausal women. NAMPT is involved in many important biological processes, including metabolism, stress response, and aging [ 39 ] (Figure S2, Supporting Information). However, gene expression measures used as input for PCA revealed stratification of the cohort into two subgroups, designated subgroups A and B. Subgroup A had higher expression of several sirtuin system gene targets compared to subgroup B. Gene expression profiles characterizing subgroup A were higher levels of NMRK1, SIRT5, NADSYN1, NMNAT1, SIRT6, PPIB, SIRT1, SIRT2, ABCA1, SIRT3, NAMPT, and PARP1 expression, and lower levels of NMRK2 and NMNAT2 .…”