Arnoldussen I A C, Wiesmann M, Pelgrim C E, Wielemaker E M, van Duyvenvoorde W, Amaral-Santos P L, Verschuren L, Keijser B J F, Heerschap A, Kleemann R, Wielinga P Y, Kiliaan A J
Department of Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Centre, Nijmegen, The Netherlands.
Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, The Netherlands.
Int J Obes (Lond). 2017 Jun;41(6):935-944. doi: 10.1038/ijo.2017.52. Epub 2017 Feb 21.
Midlife obesity affects cognition and increases risk of developing dementia. Recent data suggest that intake of the short chain fatty acid butyrate could improve memory function, and may protect against diet-induced obesity by reducing body weight and adiposity.
We examined the impact of a high-fat diet (HFD) followed by intervention with 5% (w/w) dietary butyrate, on metabolism, microbiota, brain function and structure in the low-density-lipoprotein receptor knockout (LDLr-/-) mouse model in mid and late life.
In mid-adult mice, 15 weeks of HFD-induced adiposity, liver fibrosis and neuroinflammation, increased systolic blood pressure and decreased cerebral blood flow, functional connectivity assessed with neuroimaging. The subsequent 2 months butyrate intervention restored these detrimental effects to chow-fed control levels. Both HFD and butyrate intervention decreased variance in fecal microbiota composition. In late-adult mice, HFD showed similar detrimental effects and decreased cerebral white and gray matter integrity, whereas butyrate intervention attenuated only metabolic parameters.
HFD induces detrimental effects in mid- and late-adult mice, which can be attenuated by butyrate intervention. These findings are consistent with reported associations between midlife obesity and cognitive impairment and dementia in humans. We suggest that butyrate may have potential in prevention and treatment of midlife obesity.
中年肥胖会影响认知，并增加患痴呆症的风险。近期数据表明，摄入短链脂肪酸丁酸盐可改善记忆功能，还可能通过减轻体重和肥胖来预防饮食诱导的肥胖。
我们研究了在低密度脂蛋白受体敲除（LDLr-/-）小鼠中年及老年模型中，高脂饮食（HFD）后用5%（w/w）的丁酸盐进行干预，对代谢、微生物群、脑功能和结构的影响。
在成年中期小鼠中，15周的高脂饮食导致肥胖、肝纤维化和神经炎症，收缩压升高，脑血流量减少，神经影像学评估的功能连接性降低。随后2个月的丁酸盐干预将这些有害影响恢复到正常饮食对照组的水平。高脂饮食和丁酸盐干预均降低了粪便微生物群组成的差异。在成年晚期小鼠中，高脂饮食显示出类似的有害影响，并降低了脑白质和灰质的完整性，而丁酸盐干预仅减弱了代谢参数。
高脂饮食在成年中期和晚期小鼠中诱导有害影响，而丁酸盐干预可减轻这些影响。这些发现与人类中年肥胖与认知障碍和痴呆症之间已报道的关联一致。我们认为丁酸盐可能在中年肥胖的预防和治疗中具有潜力。
