High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for In Vitro Studies

High‐fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids and induce lipotoxicity in various organs. Invitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in vivo; however, these approaches are not physiological as tissues are exposed to multiple fatty acids in vivo. Here we characterize circulating lipids in obesity‐prone rats fed an HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in vitro studies. Rats were fed an HFD (60 % kcal fat) or a control diet (10 % kcal fat) for 3 weeks; liver tissue and both portal and systemic blood were collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG) and phospholipids in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40 % lower in HFD‐fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n‐6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in vitro studies attempting to model lipid exposures that occur during in vivo HFD conditions.     

大豆不溶性膳食纤维对高脂饮食诱导小鼠肥胖的预防作用

目的:研究大豆不溶性膳食纤维(Soybean insoluble dietary fiber,SIDF)对高脂饮食(High fat diet,HFD)诱导小鼠肥胖的预防作用及其机理。方法:将50只C57BL/6J小鼠随机分为正常饮食对照组(Normal diet,ND)、高脂饮食对照组(HFD)和大豆不溶性膳食纤维低(Low-dose soybean insoluble dietary fiber,LSIDF)(250 mg/kg BW/d)、中(Middle-dose soybean insoluble dietary fiber,MSIDF)(500 mg/kg BW/d)、高剂量组(High-dose soybean insoluble dietary fiber,HSIDF)(1 g/kg BW/d),ND组饲喂正常饲料,其余各组饲喂高脂饲料,连续喂养20周。实验结束后统计体质量、肝脏和脂肪湿质量,制作肝脏组织病理切片,测定血清及肝脏脂质水平,实时荧光定量聚合酶链式反应测定小鼠肝脏中脂代谢相关基因表达水平。结果:与HFD组比,SIDF各剂量组可显著减缓小鼠体重增加,降低其血清和肝脏中总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)水平(P<0.05),并且HSIDF组效果优于LSIDF、MSIDF组;小鼠肝脏指数(P<0.05)和脂肪系数(P<0.001)显著降低,其中MSIDF和HSIDF组小鼠腹部脂肪(P<0.001)和肾周脂肪重量(P<0.001)显著减少;HSIDF组显著下调小鼠肝脏中脂肪酸合成酶(Fatty acid synthase,FAS)、二酰甘油酰基转移酶1(Diacylglycerol acyltransferase-1,DGAT1)、二酰甘油酰基转移酶2(Diacylglycerol acyltransferase-2,DGAT2)、硬脂酰辅酶A去饱和酶1(Stearyl-coenzyme A dehydrogenase-1,SCD1)基因表达水平(P<0.05),同时上调过氧化物酶体增殖物激活受体α(Peroxisome proliferators-activated receptor-α,PPARα)、肉毒碱棕榈酰基转移酶1a(Carnitine palmtoyl transferase-1a,CPT1a)基因表达水平(P<0.05)。结论:IDFS对HFD诱导小鼠肥胖具有预防作用,可能与减少脂质合成,加快脂肪酸氧化有关,其可作为一种潜在的膳食补充剂。     

鱼胶原蛋白肽对高脂膳食小鼠肝脏脂肪代谢和氧化还原状态的影响

目的：研究鱼胶原蛋白肽（fish collagen peptides,FCPs）对高脂膳食（high-fat diet,HFD）小鼠肝脏脂肪代谢和氧化还原状态的影响。方法：54?只C57BL/6雄性小鼠按体质量随机分为正常膳食组（CON）、HFD组（HF）和FCPs干预HFD组（PHF）。每周记录各组小鼠体质量,并按体质量把每组小鼠随机均分为两批,分别在第11和22周宰杀,测定采食量、脂肪表观消化率;肝脏中甘油三酯（triglyceride,TG）、总胆固醇和游离脂肪酸（free fatty acid,FFA）含量;肝脏脂代谢相关基因乙酰辅酶A羧化酶1、脂肪酸合成酶、固醇调节元件结合蛋白1c、胆固醇7α-羟化酶（cholesterol 7α-hydroxylase 1,CYP7A1）、过氧化物激活受体α（peroxisome proliferator activated receptor α,PPARα）和肉毒碱棕榈酰基转移酶1（carnitine palmity1 transferase 1,CPT1）的mRNA表达水平,肝脏氧化还原状态相关指标活性氧自由基（reactive oxygen species,ROS）、丙二醛、总抗氧化能力（total antioxidant capacity,T-AOC）、谷胱甘肽过氧化物酶（glutathion peroxidase,GSH-Px）活力和还原型/氧化型谷胱甘肽的水平。结果：第22周时,与HF组相比,PHF组小鼠的采食量、脂肪和能量摄入显著增加（P＜0.05）,肝脏的TG、FFA、脂肪空泡和脂肪浸润面积比明显降低（P＜0.05）,脂肪分解关键基因CYP7A1、PPARα和CPT1的mRNA表达水平显著上调（P＜0.05）,肝脏的ROS水平显著降低（P＜0.05）,T-AOC水平和GSH-Px活力显著升高（P＜0.05）。结论：质量分数1% FCPs干预可能通过改善HFD小鼠肝脏氧化还原状态,促进肝脏脂肪分解代谢,起到减少小鼠肝脏脂肪蓄积和改善脂代谢。     

面向数据中心网络的分层式故障诊断算法

首次提出一种面向数据中心网络的分层式故障诊断算法---HFD（Hierarchical Fault Diagnosis）算法。算法根据数据中心网络的结构特点,将网络系统分为两个逻辑层。在第一层,通过对“基本单元组”进行多次最简测试,将其划分为“相对故障单元组”与“相对正常单元组”两大类;在第二层,结合本文首次提出的“正-反关联性”思想和笔者曾经提出的“绝对故障基”思想,设计出AD-FAFD算法进行各单元间的相互测试与诊断。仿真实验结果表明,HFD算法在保持良好的诊断精确度的同时,有效降低了时间复杂度。     

The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Protects against Dyslipidemia-Related Kidney Injury in Apolipoprotein E Knockout Mice

The goal of this study was to investigate the possible protective effects of sitagliptin against dyslipidemia-related kidney injury in apolipoprotein E knockout (apoE^−/−) mice. Eight-week-old male apoE^−/− mice were randomized to receive either a high fat diet (HFD, apoE^−/− group) or HFD mixed with sitagliptin (sita + apoE^−/− group) for 16 weeks. A control group of age- and gender-matched C57BL/6J mice were fed a HFD. The apoE^−/− group exhibited increases in body weight and serum lipid levels in addition to high-density lipoprotein, and increases in 24-h urinary 8-hydroxy-2-deoxyguanosine and albuminuria excretion. Decreased insulin sensitivity was also observed in the apoE^−/− group. These mice additionally contained enlargements of the glomerular mesangial matrix area, lipid deposition area, and renal interstitium collagen area. The apoE^−/− group also demonstrated down-regulation of phosphorylated AMP-activated protein kinase (AMPK), increases in renal mRNA expression of transforming growth factor-beta 1 (TGF-β1) and fibronectin (FN), and increased protein expression of Akt, TGF-β1, FN and p38/ERK mitogen-activated protein kinase (MAPK). Sitagliptin treatment successfully ameliorated all the deleterious effects of dyslipidemia tested. To our knowledge, this is the first time that sitagliptin has been shown to reverse the renal dysfunction and structural damage induced by dyslipidemia in apoE^−/− mice. Our results suggest that the renoprotective mechanism of sitagliptin may be due to a reduction in Akt levels, a restoration of AMPK activity, and inhibition of TGF-β1, FN, and p38/ERK MAPK signaling pathways.     

Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (Cacna1d, Nlgn3, and Shank1) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.