SerumN¹-Methylnicotinamide Is Associated With Obesity and Diabetes in Chinese

Abstract

Context:Nicotinamide N-methyltransferase (NNMT) is a novel histone methylation modulator that regulates energy metabolism, and NNMT knockdown prevents diet-induced obesity in mice. However, whether NNMT plays a role in human obesity and type 2 diabetes (T2DM) remains to be elucidated.Objective: NNMT catalyzes methylation of nicotinamide to generate N 1 -methylnicotinamide (me-NAM). We aimed to investigate the associations of serum me-NAM with obesity and T2DM in Chinese.Design, Setting, and Participants: The study subjects (n ϭ 1160) were recruited from Dali, a city of Yunnan Province, in southwest China. Anthropometric phenotypes, fasting glucose, and serum lipids were measured. Serum me-NAM was measured by liquid chromatography-mass spectrometry.Results: Serum me-NAM was positively correlated with body mass index and waist circumference and negatively with high-density lipoprotein (P Յ .03). The correlations remained highly significant in the multivariate adjusted correlation analyses. In men (n ϭ 691), positive correlations between me-NAM and fasting glucose, low-density lipoprotein, liver function, and serum creatinine levels were also observed in both simple and multivariate adjusted correlation analyses. In multiple logistic regression analyses, elevated serum me-NAM was associated with higher risks for overweight/obesity (odds ratios, 2.36 and 5.78; 95% confidence intervals, 1.10 -5.08 and 1.78 -18.76 for men and women, respectively; P Յ .03) and diabetes (odds ratios, 1.56 and 1.86; 95% confidence intervals, 1.10 -2.22 and 1.05-3.31 for men and women, respectively; P Յ .03). Conclusions:This first large-scale population study shows that me-NAM, as an indicator of NNMT activity, is strongly associated with obesity and diabetes, supporting NNMT as a potential target for treating obesity and diabetes in humans. (J Clin Endocrinol Metab 100: 3112-3117, 2015)

Nicotinamide N -Methyltransferase: More Than a Vitamin B3 Clearance Enzyme

“…No association between NNMT expression and BMI was found in this study, as has been suggested by rodent data [38]. In contrast, Liu and colleagues reported a positive correlation between circulating MNAM and BMI, waist and hip circumference (BMI r = 0.22, p < 0.001 in men; r = 0.13, p = 0004 in women) in a larger cohort of 1160 Chinese individuals [19]. Curiously, the average BMI in the study by Kaant and colleagues was in between 33 and 47 for control and T2D individuals, respectively.…”

“…Human adipose tissue NNMT expression correlates positively with adiposity and insulin resistance [18,19]. Consistent with these correlations, antisense NNMT knockdown (NNMT ASO) in vivo protected C57BL6 mice from fat accumulation on a high fat diet (HFD) and improved their glucose tolerance compared with controls [38].…”

“…Two recent studies extend these findings to humans and show that adipose tissue NNMT and its circulating product MNAM correlates positively with insulin resistance and body mass index (BMI) [18,19]. In the study by Kannt and colleagues, NNMT expression is increased ~2-fold in subcutaneous and omental adipose tissue of type 2 diabetic subjects (men and women), compared to healthy controls.…”

Serum N 1 ‐Methylnicotinamide is Associated With Coronary Artery Disease in Chinese Patients

“…[4][5][6] Our recent epidemiological study also revealed that serum me-NAM, an indicator of NNMT activity, was associated with obesity and diabetes mellitus in a Chinese population. 7 Because obesity and diabetes mellitus were independent risk factors for the development of CAD, 8,9 we hypothesized that increased serum me-NAM levels might be associated with CAD. Indeed, upregulation of hepatic NNMT activity and subsequent increase in plasma me-NAM levels were associated with the progression of atherosclerosis in an animal model.…”

Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia

“…Kraus et al [7] reported that NNMT expression is increased in white adipose tissue (WAT) and liver of obese and diabetic mice, and NNMT knockdown in WAT and liver protects against diet-induced obesity by increasing cellular energy expenditure. Liu et al [8] found that serum MNA was associated with obesity and diabetes. Hong et al [9] showed that nicotinamide N-methyltransferase regulated hepatic nutrient metabolism.…”