Association between Nicotinamide Phosphoribosyltransferase and de novo Lipogenesis in Nonalcoholic Fatty Liver Disease

Abstract

Objective: This study explored the association between serum nicotinamide phosphoribosyltransferase (NAMPT) and hepatic de novo lipogenesis (DNL) in nonalcoholic fatty liver disease (NAFLD) and determined whether or not this association is sex dependent. Subjects and Methods: In this cross-sectional study, 62 consecutive patients (32 males, 30 females) with NAFLD were recruited. Serum NAMPT (by ELISA), palmitic acid, and the DNL index of erythrocyte membranes as markers of hepatic DNL (by gas chromatography) were analyzed. The controlled attenuation parameter (CAP) and body impedance analyzer were used to assess hepatic and body fat, respectively. Univariate and multiple linear regressions (to adjust for confounders) were used to analyze the association of serum NAMPT with palmitic acid, DNL index, CAP, and body fat. Results: The respective values of serum NAMPT (2.44 ± 1.03 vs. 2.45 ± 1.13 ng/mL, p = 0.98), DNL index (3.11 [2.60-3.71] vs. 3.05 [2.40-3.59], p = 0.90), and palmitic acid (20.55% [15.34-24.04] vs. 22.64% [21.15-25.95], p = 0.07) were not significantly different between men and women, but those of CAP (326 [300-340] vs. 300 [261.25-329], p = 0.002) and body fat (37.71 ± 3.80 vs. 26.60 ± 5.70, p < 0.001) were significantly higher in women. In women, serum NAMPT had a significant negative association with the DNL index (β = -0.56, p = 0.01). The DNL index also had a significant negative association with body fat (β = -0.46, p = 0.02). In men, the only significant association was the positive association between serum NAMPT and CAP (β = 0.35, p = 0.035). Conclusion: Higher serum NAMPT in women was associated with a lower hepatic DNL index, while in men it was associated with higher hepatic fat and had no association with the DNL index. Therefore, the serum NAMPT level interpretation for NAFLD prognosis is probably sex dependent.

NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential

“…447 It was found that higher level of NAMPT in serum in women is correlated with a much lower hepatic de novo lipogenesis (DNL) index, although they do not correlate with the DNL index, but had a correlation with a higher hepatic fat in men, implying a sex-dependent interpretation role of serum NAMPT level for NAFLD prognosis. 471 Mechanistically, reduced NAMPT/NAD + inhibits SIRT1's function, thereby attenuating the deacetylation activity of SREBP1, leading to the expression of ACC and FASN. 463 Conversely, stabilization of SIRT1 by increasing NNMT expression or MNAM levels improves lipid parameters.…”

Relationship between Oxidative Stress, Inflammation and Dyslipidemia with Fatty Liver Index in Patients with Type 2 Diabetes Mellitus

“…Non-alcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver diseases [1] and is tightly associated with insulin resistance [2,3]. Therefore, the high prevalence of this metabolic disorder observed in individuals with obesity or type 2 diabetes mel-litus (DM2), [4] is not suprising.…”

Nicotinamide and NAFLD: Is There Nothing New Under the Sun?

“…Gaddipati et al [64] showed that a significant reduction in the NAMPT levels of the visceral adipose tissue is associated to degree of steatosis in NAFLD patients. Similarly, Amirkalali et al [68] showed that higher serum NAMPT is associated with lower liver DNL in female subjects (probably associated with a higher adipose tissue DNL according to the higher fat mass), while the only significant association in male subjects was between serum NAMPT and liver fat content, probably for the inflammatory role of NAMPT. Thus, the plasma NAMPT levels could have a different meaning for each sex because of the opposing effects of liver and adipose tissue DNL on NAFLD pathogenesis.…”

“…Several studies evaluated the relationship between NAD metabolism and NAFLD [29,64,65,66,67,68] (Table 1). Human studies investigated how plasma and liver NAMPT protein levels are affected in subjects with steatosis and NAFLD [64,65,66,67,68]. Gaddipati et al [64] showed that a significant reduction in the NAMPT levels of the visceral adipose tissue is associated to degree of steatosis in NAFLD patients.…”