Ming Liu1, Lihua Li1, Jihong Chu1, Boyu Zhu1, Qingtao Zhang1, Xueyan Yin1, Weimin Jiang1, Guoliang Dai1, Wenzheng Ju1, Zhenxing Wang1, Qin Yang1, Zhuyuan Fang1. 1. Department of Cardiology (M.L., W.J., Z.W., Z.F.), Department of Clinical Pharmacology (J.C., G.D., W.J.), and Department of Endocrinology (B.Z.), Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu, China; Department of Medicine, Physiology and Biophysics, Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism (M.L., Q.Y.), University of California Irvine, Irvine, California 92697; and Department of Internal Medicine (L.L., Q.Z., X.Y.), Dali University School of Clinical Medicine, Dali 671003, Yunnan, China.
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 = 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 ≤ .03). The correlations remained highly significant in the multivariate adjusted correlation analyses. In men (n = 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 ≤ .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 ≤ .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.
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 humanobesity 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 = 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 ≤ .03). The correlations remained highly significant in the multivariate adjusted correlation analyses. In men (n = 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 ≤ .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 ≤ .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.
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