Mehus Aaron A, Rust Bret, Idso Joseph P, Hanson Benjamin, Zeng Huawei, Yan Lin, Bukowski Michael R, Picklo Matthew J
USDA-ARS Grand Forks Human Nutrition Research Center Grand Forks, North Dakota, USA; Department of Pathology, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, North Dakota, USA.
USDA-ARS Grand Forks Human Nutrition Research Center Grand Forks, North Dakota, USA.
J Nutr Biochem. 2021 Feb;88:108531. doi: 10.1016/j.jnutbio.2020.108531. Epub 2020 Oct 22.
Time-restricted feeding (TRF) can reduce adiposity and lessen the co-morbidities of obesity. Mice consuming obesogenic high-fat (HF) diets develop insulin resistance and hepatic steatosis, but have elevated indices of long-chain polyunsaturated fatty acids (LCPUFA) that may be beneficial. While TRF impacts lipid metabolism, scant data exist regarding the impact of TRF upon lipidomic composition of tissues. We (1) tested the hypothesis that TRF of a HF diet elevates LCPUFA indices while preventing insulin resistance and hepatic steatosis and (2) determined the impact of TRF upon the lipidome in plasma, liver, and adipose tissue. For 12 weeks, male, adult mice were fed a control diet ad libitum, a HF diet ad libitum (HF-AL), or a HF diet with TRF, 12 hours during the dark phase (HF-TRF). HF-TRF prevented insulin resistance and hepatic steatosis resulting from by HF-AL treatment. TRF-blocked plasma increases in LCPUFA induced by HF-AL treatment but elevated concentrations of triacylglycerols and non-esterified saturated fatty acids. Analysis of the hepatic lipidome demonstrated that TRF did not elevate LCPUFA while reducing steatosis. However, TRF created (1) a separate hepatic lipid signature for triacylglycerols, phosphatidylcholine, and phosphatidylethanolamine species and (2) modified gene and protein expression consistent with reduced fatty acid synthesis and restoration of diurnal gene signaling. TRF increased the saturated fatty acid content in visceral adipose tissue. In summary, TRF of a HF diet alters the lipidomic profile of plasma, liver, and adipose tissue, creating a third distinct lipid metabolic state indicative of positive metabolic adaptations following HF intake.
限时进食（TRF）可以减少肥胖并减轻肥胖的合并症。食用致肥胖的高脂（HF）饮食的小鼠会出现胰岛素抵抗和肝脂肪变性，但长链多不饱和脂肪酸（LCPUFA）指数升高，这可能是有益的。虽然TRF会影响脂质代谢，但关于TRF对组织脂质组组成影响的数据却很少。我们（1）测试了以下假设：高脂饮食的TRF可提高LCPUFA指数，同时预防胰岛素抵抗和肝脂肪变性；（2）确定了TRF对血浆、肝脏和脂肪组织脂质组的影响。在12周的时间里，成年雄性小鼠被随意喂食对照饮食、随意喂食高脂饮食（HF-AL）或在黑暗期的12小时内喂食高脂饮食并进行TRF（HF-TRF）。HF-TRF预防了HF-AL治疗导致的胰岛素抵抗和肝脂肪变性。TRF阻止了HF-AL治疗诱导的血浆LCPUFA增加，但提高了三酰甘油和非酯化饱和脂肪酸的浓度。肝脏脂质组分析表明，TRF在减少脂肪变性的同时并没有提高LCPUFA。然而，TRF产生了（1）三酰甘油、磷脂酰胆碱和磷脂酰乙醇胺种类的独特肝脏脂质特征，以及（2）与脂肪酸合成减少和昼夜基因信号恢复一致的基因和蛋白质表达改变。TRF增加了内脏脂肪组织中的饱和脂肪酸含量。总之，高脂饮食的TRF改变了血浆、肝脏和脂肪组织的脂质组特征，创造了第三种独特的脂质代谢状态，表明高脂摄入后有积极的代谢适应性。
