Biomedical Sciences Graduate Program, Hermínio Ometto Foundation University Center (FHO), Araras, SP, Brazil.
Biomedicine College, Hermínio Ometto Foundation University Center (FHO), Araras, SP, Brazil.
Can J Physiol Pharmacol. 2021 Apr;99(4):439-447. doi: 10.1139/cjpp-2020-0195. Epub 2020 Aug 27.
Nicotinamide adenine dinucleotide (NAD) precursors such as nicotinamide activate sirtuins and enhance energy metabolism. The aim of this study was to evaluate the metabolic effects of nicotinamide in ovariectomized (OVX) female rats to establish molecular targets against obesity, which support the safe therapeutic application of nicotinamide. The OVX animals were divided into groups: SHAM (simulated surgery), SHAMn (two weeks of 35 mg·kg nicotinamide per day, by gavage), OVX, and OVXn (two weeks of 35 mg·kg nicotinamide per day, by gavage). The results indicated that nicotinamide favored lipolysis, as evidenced by an increase in free fatty acid and hepatic triglyceride levels, which were not fully normalized during the treatment period. The lipolysis appeared to be due to increased SIRT1 and mitochondrial oxidative phosphorylation in muscle and adipose tissue. There were decreases in muscle and fat nicotinamide -methyltransferase (NNMT), which were associated with decreases in mass and triglyceride, low-density lipoprotein cholesterol (LDLc), and total cholesterol content. Nicotinamide appeared to be beneficial for the glycemic profile, with normal hepatic glycogen storage and a tendency towards insulin sensitivity in the OVXn. In the SHAMn group, nicotinamide led to glucose intolerance, together with reduced muscle expressions of nicotinamide phosphoribosyltransferase (NAMPT) and SIRT3, suggesting that there were no short-term benefits. Supplementation with nicotinamide led to tissue-specific adaptive lipid and molecular changes in OVX rats.
烟酰胺腺嘌呤二核苷酸 (NAD) 前体如烟酰胺可激活沉默调节蛋白并增强能量代谢。本研究旨在评估烟酰胺对去卵巢（OVX）雌性大鼠的代谢影响，以确定针对肥胖的分子靶点，这支持烟酰胺的安全治疗应用。OVX 动物分为以下几组：SHAM（模拟手术）、SHAMn（每天灌胃 35mg·kg 烟酰胺两周）、OVX 和 OVXn（每天灌胃 35mg·kg 烟酰胺两周）。结果表明，烟酰胺有利于脂肪分解，这表现为游离脂肪酸和肝甘油三酯水平的增加，而在治疗期间并未完全恢复正常。脂肪分解似乎是由于肌肉和脂肪组织中 SIRT1 和线粒体氧化磷酸化增加所致。肌肉和脂肪中的烟酰胺 -N- 甲基转移酶（NNMT）减少，这与质量和甘油三酯、低密度脂蛋白胆固醇（LDLc）和总胆固醇含量减少有关。烟酰胺似乎对血糖谱有益，肝糖原储存正常，OVXn 组胰岛素敏感性有增加趋势。在 SHAMn 组中，烟酰胺导致葡萄糖不耐受，同时肌肉中烟酰胺磷酸核糖基转移酶（NAMPT）和 SIRT3 的表达减少，表明没有短期益处。补充烟酰胺可导致 OVX 大鼠组织特异性的适应性脂质和分子变化。
