Abdulsada Mustafa M, Wilhelm Zoe R, Opekun Antone R, Devaraj Sridevi, Jalal Prasun K, Mindikoglu Ayse L
Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA.
Clinical Chemistry and Point of Care Technology, Texas Children's Hospital and Health Centers, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Metabol Open. 2020 Dec 4;9:100070. doi: 10.1016/j.metop.2020.100070. eCollection 2021 Mar.
Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that regulates food intake and energy hemostasis. BDNF also promotes neurogenesis, neuroplasticity, and neuroprotection. There are conflicting reports regarding how intermittent fasting affects circulating BDNF levels. We tested the hypothesis that 4-week intermittent fasting from dawn to sunset (4-week-IF) would decrease circulating BDNF levels in subjects with metabolic syndrome and healthy subjects.
We conducted pilot studies in subjects with metabolic syndrome and healthy subjects who fasted from dawn to sunset for more than 14 h for four consecutive weeks. We measured serum BDNF levels and metabolic parameters before 4-week-IF, at the end of 4th week during 4-week-IF, and one week after 4-week-IF.
We enrolled 28 subjects, 14 with metabolic syndrome (women/men:6/8) with a mean age of 59 years and 14 healthy subjects (women/men:1/13) with a mean age of 32 years. Overall, BDNF levels decreased at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (mean paired difference = -98.5 ng/ml, P = 0.0006). When subjects with metabolic syndrome were compared with healthy subjects, subjects with metabolic syndrome had a lower mean paired reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (BDNF mean paired difference = -27.6 ng/ml vs. -169.5 ng/ml, P = 0.003). Multivariate linear regression analysis showed a positive correlation between the change in tumor necrosis factor-alpha and change in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome (P = 0.040) and healthy subjects (P = 0.007). The change in weight and body mass index independently predicted the change in BDNF levels 1 week after 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome.
Four-week-IF resulted in a reduction in the BDNF levels at the end of 4th week during 4-week-IF. Higher BDNF levels and a lower reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome than healthy subjects suggest a potential BDNF resistance similar to insulin and leptin resistance in metabolic syndrome. A positive correlation between the change in BDNF and change in tumor necrosis factor-alpha levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF suggests that BDNF is a biomarker of inflammation and endothelial dysfunction in addition to its neurotrophic and anorexigenic features.
脑源性神经营养因子（BDNF）是一种关键的神经营养因子，可调节食物摄入和能量稳态。BDNF还能促进神经发生、神经可塑性和神经保护。关于间歇性禁食如何影响循环BDNF水平，存在相互矛盾的报道。我们检验了这样一个假设：连续四周从黎明到日落进行间歇性禁食（4周间歇性禁食，4-week-IF）会降低代谢综合征患者和健康受试者的循环BDNF水平。
我们对代谢综合征患者和健康受试者进行了初步研究，这些受试者连续四周从黎明到日落禁食超过14小时。我们在4周间歇性禁食前、4周间歇性禁食第4周结束时以及4周间歇性禁食后一周测量血清BDNF水平和代谢参数。
我们招募了28名受试者，其中14名患有代谢综合征（女性/男性：6/8），平均年龄59岁，14名健康受试者（女性/男性：1/13），平均年龄32岁。总体而言，与4周间歇性禁食前相比，4周间歇性禁食第4周结束时BDNF水平下降（平均配对差异=-98.5 ng/ml，P=0.0006）。将代谢综合征患者与健康受试者进行比较时，与4周间歇性禁食前相比，代谢综合征患者在4周间歇性禁食第4周结束时BDNF水平的平均配对降低幅度较小（BDNF平均配对差异=-27.6 ng/ml对-169.5 ng/ml，P=0.003）。多变量线性回归分析显示，与4周间歇性禁食前相比，代谢综合征患者和健康受试者在4周间歇性禁食第4周结束时，肿瘤坏死因子-α的变化与BDNF水平的变化呈正相关（代谢综合征患者P=0.040，健康受试者P=0.007）。在代谢综合征患者中，与4周间歇性禁食前相比，体重和体重指数的变化独立预测了4周间歇性禁食后1周BDNF水平的变化。
4周间歇性禁食导致4周间歇性禁食第4周结束时BDNF水平降低。与健康受试者相比，代谢综合征患者在4周间歇性禁食第4周结束时BDNF水平较高且降低幅度较小，这表明存在类似于代谢综合征中胰岛素和瘦素抵抗的潜在BDNF抵抗。与4周间歇性禁食前相比，4周间歇性禁食第4周结束时BDNF变化与肿瘤坏死因子-α水平变化之间的正相关表明，BDNF除具有神经营养和抑制食欲功能外，还是炎症和内皮功能障碍的生物标志物。
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