Calorie restriction potentiates epigallocatechin-3-gallate-mediated Nrf2 activation in hepatocytes of aged rats

Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antioxidant defense system of aged rats.Methods:Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days.The initial body weight of aged rats was recorded,and the final body weight was measured at the end of the experimental period.Serum lipid and lipoprotein status,oxidative stress markers such as free radicals and malondialdehyde levels,and reduced glutathione were assessed.In addition,RT-PCR and Western blotting analyses were performed.Results:Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status,improving the levels of serum lipid and lipoproteins,upregulating Nrf2 and Bcl2,and downregulating Keap1,cullin3,Bax and cytochrome c in aged rats.Conclusions:Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats.This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging,thereby reducing the risk for age-associated degenerative diseases.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Pivotal role of SIRT6 in calorie restriction, aging and inflammation

Background The aggravating trend of aging population has brought us with great medical challenges. Calorie restriction （CR） has various beneficial effects on health, including lifespan prolongation and functional im- provement of multiple organisms. SIRT6, a member of the Sirtuin family of NAD^＋-dependent histone deacetylases, has been shown to play a key role in mediating the effects of CR. Aim Here we show how CR-triggered SIRT6-de- pendent pathways affect aging and the critical role of SIRT6 on inflammation. Methods 24-month-old mice were fed under ad libitum （AL） or CR condition for 6 months to determine the effects of CR. In addition, we took low glucose （LG） cultured WI38 human fibroblasts as a model to mimic CR in vitro. Further more, we stably overex- pressed or knockdown SIRT6 in WI38 to identify the role of SIRT6 in cell senescence and inflammation. Results Aged mice with CR had improved renal pathology and enhanced SIRT6 expression compared with AL group. In ad- dition, compared with normal glucose （NG） group, LG group had prolonged lifespan and increased expression of SIRT6. Furthermore, increased SA-β-gal positive cells were observed in SIRT6-deficient cells while the overexpres- sion of SIRT6 could delay the replicative senescence effectively. NF-KB was involved in the SIRT6 mediated lon- gevity control. SIRT6 overexpressed WI38 had low translocate rate of NF-KB into the nucleus and SIRT6 could at- tenuate the NF-KB signaling by deacetylating the RelA subunit of NF-KB complex. Conclusion In this study, we show that CR prevents age-dependent renal insufficiency by up-regulation of SIRT6. CR-triggered SIRT6 activation suppresses NF-KB signaling via preventing nuclear translocation of NF-KB. Here we identified the beneficial effects of CR on renal aging and determined the crucial role of SIRT6 on CR-mediated lifespan extension.

Changes Induced by Physical Activity, Weight Loss and Calorie Restriction in Body Composition, Lipoproteins and Functional Capacity in Obese Congolese Women

Background. The effects of physical exercises combined with a low-calorie diet on weight loss, body composition, lipoproteins profile, and physical fitness had been well described. However, Central Africa’s studies investigating these kinds of diets and exercise regimens are lacking. Objective. To investigate the effects of adding 14-weeks exercises to a hypocaloric diet on changes in body composition, lipoproteins concentrations, and physical capacities in obese Congolese women. Population and Methods. In total, 34 obese women aged 30 - 39 years (mean age: 33.7 ± 2.4 years) assigned to 14-weeks training program and low energy ketogenic diet. Body composition was assessed using classic methods and impedancemetry. Fasting plasma glucose (FPG) and fasting serum insulin were assessing using enzymatic colorimetric and radioim-munoradiometric methods. HOMA-IR and lipoproteins concentrations were assessed using standardized laboratory methods. VO2peak was measured on a treadmill during a progressive exercise test. Speed, cadence and stride length were measured along the 10-m level walkway. Muscular endurance was measured using the tests of sit-up and inflections-extensions of elbows. All the variables of the study were assessed at the beginning, in the 7-weeks, and in the 14-weeks of training methods. Results. Declines in body weight (16%), percent fat (12.1%), fat weight (26.4%), abdominal fat (34.2%), and waist circumference (10.4%) were found. A significant decrease in FPG (13%), fasting serum insulin (60.9%), HOMA-IR (64.7%), total cholesterol (12.2%), LDL-cholesterol (20.3%), triglycerides (92.8%), and VLDL-triglycerides (17.5%) was shown. In contrast, significant increase in HDL-cholesterol (27.13%) was found. The peak oxygen consumption VO2peak relative to body weight improved more in the 14-weeks training program (13.4%). Obese women exhibited higher values in the 14-weeks training program for speed gait (16.5%), cadence (9.1%), and stride length (15.7%) during normal walk and rapid walk. Weight loss combined with a low-calorie diet and 14-weeks training program improved significantly muscular endurance capacities. Conclusion. Exercise added to hypocaloric diet leads to decreases in body composition, to improve in insulin sensitivity, to enhancement of VO2peak and functional fitness. This may be helpful for the treatment of the metabolic complications of abdominal obesity.

基于CiteSpace和VOSviewer可视化软件对饮食限制调控炎症的研究现状与热点分析

目的:基于CiteSpace和VOSviewer可视化软件对饮食限制(DR)调控炎症文献进行定量可视化分析,探索DR调控炎症领域的研究热点和趋势。方法:检索2010年1月1日至2022年9月29日Web of Science核心数据库中收录的DR调控炎症相关文献共1678篇,经筛查最终获得1344篇,使用CiteSpace和VOSviewer可视化软件对检索到的文献数据进行年发文量、国家、机构、作者、被引频次和关键词的定量和可视化分析。结果:最终获得的1344篇文献年发文量总体呈上升趋势,文献最高被引频次为1676次,美国(481篇)是出产文献数量最多的国家,中国(181篇)位居第二。DR调控炎症领域研究热点集中在热量限制(CR)、生酮饮食、衰老、代谢性疾病、脂肪组织及肠道菌群等方面。结论:DR调控炎症愈来愈受到国际和国内研究者青睐,未来研究热点可能是CR模拟物(CRM)、肠道菌群、神经退行性疾病和心血管疾病,总体研究趋势为进一步明确DR的抗炎机制,寻找新的治疗靶点,将更多经过体外和动物模型证实的有效方案进行更严格的临床试验。

热量限制疗法在心力衰竭病人中的应用进展

结合近年来国内外研究进展,对热量限制(caloric restriction,CR)疗法的概念、CR疗法对心力衰竭(HF)的潜在作用机制及其干预效果进行综述,旨在为临床工作者构建HF病人的健康营养管理策略提供参考。

限能量膳食方案联合低强度连续运动在妊娠期糖尿病患者血糖控制中的应用

目的:探讨给予妊娠期糖尿病(GDM)患者限能量膳食(CRD)方案联合低强度连续运动在血糖控制中的应用效果。方法:选取2022年6月—2023年6月北京怀柔医院收治的GDM患者共计350例,以干预方法的不同分成研究组(175例)与对照组(175例),对照组给予常规干预,研究组给予CRD方案联合低强度连续运动干预,比较两组血糖水平、血脂水平、胰岛素使用情况、分娩方式、母婴结局及生活质量。结果:干预后两组糖化血红蛋白(HbA1c)、餐后2 h血糖(2 h PG)、空腹血糖(FPG)水平均下降,研究组均较对照组低,差异均有统计学意义(P<0.05);干预后两组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平均下降,研究组均较对照组低,差异均有统计学意义(P<0.05);研究组胰岛素使用率、剖宫产率均较对照组低,差异均有统计学意义(P<0.05);研究组不良母婴结局发生率21.71%(38/175)较对照组的33.71%(59/175)低,差异有统计学意义(P<0.05);干预后两组糖尿病特异性生存质量量表(DSQL)评分均下降,研究组较对照组低,差异均有统计学意义(P<0.05)。结论:给予GDM患者CRD方案联合低强度连续运动,能够调节血糖、血脂水平,改善胰岛素使用情况,降低剖宫产率、不良母婴结局发生率,提高患者生活质量。

高膳食纤维限能干预对肥胖合并糖耐量异常患者体重和代谢指标的影响

目的探究高膳食纤维限能干预对肥胖合并糖耐量异常患者体重和代谢指标的影响。方法前瞻性选取陕西省中医医院营养科门诊收治的60例肥胖合并糖耐量异常患者为研究对象,采用随机数字表法将其分为高膳食纤维限能组(30例,高膳食纤维限能干预)和常规饮食限能组(30例,常规饮食限能)。比较两组的干预效果。结果干预后,高膳食纤维限能组的甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、餐后2 h血糖(2 h PG)水平及稳态模型胰岛素抵抗指数(HOMA-IR)优于常规饮食限能组(P<0.05)。干预后,高膳食纤维限能组的腰围、体质量指数(BMI)、体脂率、内脏脂肪指数小于常规饮食限能组(P<0.05)。高膳食纤维限能组的治疗有效率高于常规饮食限能组,差异具有统计学意义(P<0.05)。结论高膳食纤维限能干预在肥胖合并糖耐量异常患者中的效果较好,可改善体重和代谢指标。

Intermittent energy restriction in type 2 diabetes: A short discussion of medication management

AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane library for original research articles investigating the use of very low calorie diets(VLCD) in people with T2 DM. The search terms used included "VLCD" or "very low energy diet" or "very low energy restriction" or "IER" or "intermittent fasting" or "calorie restriction" or "diabetes mellitus type 2" and "type 2 diabetes". Reference lists of selected articles were also screened for relevant publications. Only research articles written in English, which also included an explanation of medication changes were included. A recent pilot trial using the 5:2 IER method, conducted by our research group, will also be summarized.RESULTS A total of 8 studies were found that investigated the use of VLCD in T2 DM and discussed medication management. Overall these studies indicate that the use of a VLCD for people with T2 DM usually require the cessation of medication to prevent hypoglycemia. Therefore, the 5:2 IER method will also require medication changes, but as seen in our pilot trial, may not require total cessation of medication, rather a cessation on the 2 IER days only. CONCLUSION Guidelines outlined here can be used in the initial stages of a 2-d IER diet, but extensive blood glucose monitoring is still required to make the necessary individual reductions to medications in response to weight loss.

Expression of Sirt1 and Sirt2 in the Injured Optic Retina of Calorie-Restricted Rats

Purpose:To investigate retinal ganglion cell (RGC) survival after optic nerve injury in calorie-restricted (CR) rats,and analyze the potential role of Sirtuins.Methods:Ten-month old male Sprague-Dawley rats (n=14) were divided into calorie restricted (CR) and ad libitum (AL) groups.In the CR group (n=7),the rats were denied access to food every other day.Animals in the AL group (n=7) had had free access to food.PN-ON grafting was carried out on the right eye of all subjects after 5 months of feeding.Three weeks postoperatively,retina samples were collected,half of which were fixed in 4% paraformaldehyde (PFA) and subjected to standard immunofluorescence staining for TUJ-1.The remaining samples were subjected to total RNA analysis and RT-PCR for Sirt1 and 2 expression.Results:Comparing the amount of TUJ-1 staining between the groups,the mean density and the total number of RGCs showed no significant difference.RT-PCR results indicated that mRNA expression of Sirtuin2 in the CR group was significantly lower than that in the AL group,whereas no statistically significant difference was observed between the two groups regarding the mRNA expression of Sirt1.Conclusion:Calorie restriction had no impact on the survival of injured RGCs.The down-regulated mRNA expression of Sirt2 in the CR group may indicate an improved capacity for regeneration among these animals,but more work is needed to explore this possibility.

代谢相关脂肪性肝病基于中国居民膳食指南的个体化干预研究

背景代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)在全球范围内广泛流行,不良的饮食生活习惯与其发生发展密切相关,通过饮食运动及生活方式干预是防治MAFLD的重要措施之一,但目前关于MAFLD的饮食运动及生活方式的干预策略尚无定论,其方式方法仍需要进一步研究.目的基于中国居民膳食指南为MAFLD患者制定个体化膳食及运动处方,探索个体化限制能量平衡膳食联合运动指导的干预方式对改善MAFLD的作用.方法根据是否接受个体化饮食运动干预分为干预组和对照组,分别在入组时(T0)收集患者的人体测量指标、实验室检测指标,通过问卷调查了解患者的一般信息、家族史、膳食及生活习惯、食物频率等,根据患者实际情况给予干预组患者个体化膳食处方和运动处方,对照组给予常规健康宣教,6 mo后(T1)再次收集患者的资料,比较干预前后人体测量指标和实验室检测指标的变化.结果127例MAFLD患者(对照组32例,干预组95例)中,汽车出行者占62.99%,久坐者(>8 h/d)占48.82%,饮食口味重者占比>50%,爱加餐者占37.01%;食物因子分析提取五个主因子,分别解释为“菌蔬”因子、“粮乳”因子、“肉蛋”因子、“水产”因子和“零食”因子,其中“肉蛋”因子的上五分位(Q5)可使高甘油三酯和高胆固醇的危险性分别增加为其下五分位(Q1)的5.60倍(95%CI:1.41-22.24)和6.45倍(95%CI:1.51-27.63);水产因子的中五分位(Q3)可使高胆固醇的危险性增加为其Q1的4.54倍(95%CI:1.10-18.78);干预组和对照组的人体测量指标和实验室检测指标(除对照组的糖化血红蛋白)在干预前后的差异均有统计学意义(P<0.05),且两组指标的变化差值间的差异有统计学意义(P<0.05).结论基于中国居民膳食指南个体化制定膳食及运动干预方案有助于降低MAFLD患者的体重、体质指数、腰围、内脏脂肪面积、体脂比等人体测量指标,可有效改善患者糖脂代谢状况.

抑制性能量消耗模型在减肥领域的应用前瞻

运动和热量限制作为目前公认的控制肥胖的安全有效方式,直接参与调节机体的能量收支平衡,其作用机理与抑制性能量消耗模型(constrained model of energy expenditure,CMEE)理论密切相关。CMEE模型理论认为,人体的运动量及热量限制与能量消耗之间并不是简单的等比例或线性关系,它们之间存在动态的、非线性的复杂关系。研究认为,机体内存在能量代谢的保护性机制或能量代偿模式是CMEE模型理论的核心观点,“节俭基因表型”假说是CMEE模型的重要理论支撑。人体的节俭型能量分配体系导致了肥胖症的易感性和流行性,激活加强能量代谢相关基因表达的运动量可能存在阈值。

加味苓桂术甘汤联合热量限制改善动脉粥样硬化的实验研究

目的:研究加味苓桂术甘汤联合热量限制对apoE^(-/-)小鼠动脉粥样硬化的影响。方法:C57BL/6小鼠为正常对照组,普通饲料喂养,apoE^(-/-)小鼠随机分成模型组、加味苓桂术甘汤组、单纯限食组、中药限食组,其中模型组与加味苓桂术甘汤组以高脂饲料喂养,单纯限食组、中药限食组每日按模型组50%热量投饲高脂饲料,中药限食组和加味苓桂术甘汤组给予加味苓桂术甘汤液2 mL灌胃,其余各组予以等量生理盐水灌胃。12周后,采血及留取胸主动脉,分别采用酶联免疫吸附试验(ELISA)检测血脂、炎症介质水平,苏木精-伊红(HE)染色观察管腔内粥样斑块,蛋白质印迹法(Western Boltting)检测血脂、炎症介质及主动脉腺苷一磷酸活化蛋白激酶、磷酸化腺苷一磷酸活化蛋白激酶、过氧化物酶体增殖物激活受体α、核因子κB、p-核因子κB蛋白表达。结果:与模型组比较,加味苓桂术甘汤组、单纯限食组与中药限食组动脉粥样硬化病变减轻,斑块面积与管腔面积比值明显降低(P<0.05或P<0.01),血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、肿瘤坏死因子-α、白细胞介素-6及白细胞介素-1β浓度均显著低于模型组(P<0.05或P<0.01),而中药限食组动脉粥样硬化病变最轻,斑块面积与管腔面积比值最低。蛋白质免疫印迹法显示中药限食组磷酸化腺苷一磷酸活化蛋白激酶、过氧化物酶体增殖物激活受体α蛋白表达显著升高(P<0.01),而p-核因子κB蛋白表达显著下降(P<0.01)。结论:加味苓桂术甘汤联合热量限制具有抗动脉粥样硬化作用,其机制可能是通过降低血脂、减轻炎症反应,激活腺苷一磷酸活化蛋白激酶/过氧化物酶体增殖物激活受体α信号通路,从而抑制核因子κB活性,有效发挥抗动脉粥样硬化作用。

Artemisinin mimics calorie restriction to extend yeast lifespan via a dual-phase mode: a conclusion drawn from global transcriptome profiling

Calorie restriction(CR) promotes longevity among distinct organisms from yeast to mammals. Although CR-prolonged lifespan is believed to associate with enhanced respiratory activity, it is apparently controversial for accelerated energy consumption regardless of insufficient nutrient intake. In reconciling the contradiction of less food supply versus much metabolite dispense, we revealed a CR-based mode of dual-phase responses that encompass a phase of mitochondrial enhancement(ME) and a phase of post-mitochondrial enhancement(PME), which can be distinguished by the expression patterns and activity dynamics of mitochondrial signatures. ME is characterized by global antioxidative activation, and PME is denoted by systemic metabolic modulation. CR-mediated aging-delaying effects are replicated by artesunate, a semi-synthetic derivative of the antimalarial artemisinin that can alkylate heme-containing proteins, suggesting artesunate-heme conjugation functionally resembles nitric oxide-heme interaction. A correlation of artesunate-heme conjugation with cytochrome c oxidase activation has been established from adduct formation and activity alteration. Exogenous hydrogen peroxide also mimics CR to trigger antioxidant responses, affect signaling cascades, and alter respiratory rhythms, implying hydrogen peroxide is engaged in lifespan extension. Conclusively, artesunate mimics CR-triggered nitric oxide and hydrogen peroxide to induce antioxidative networks for scavenging reactive oxygen species and mitigating oxidative stress, thereby directing metabolic conversion from anabolism to catabolism, maintaining essential metabolic functionality, and extending life expectancy in yeast.

CRD联合肠道微生态制剂对超重/肥胖不孕患者新鲜周期胚胎移植妊娠结局的影响

目的探讨限制能量平衡膳食模式(CRD)联合肠道微生态制剂对超重/肥胖不孕患者行新鲜周期胚胎移植妊娠结局的影响。方法选取2019年1月至2021年12月于该院行体外受精/卵细胞质内单精子显微注射-胚胎移植助孕新鲜胚胎移植的197例患者为研究对象,根据BMI大小和是否接受CRD干预分为超重干预组(n=46)、超重对照组(n=85)、肥胖干预组(n=29)、肥胖对照组(n=37),比较各组妊娠结局相关指标及干预前后体重和体成分变化。结果与干预前相比,超重干预组体重[(63.59±4.90)kg vs.(67.47±5.10)kg]、BMI[(25.74±1.26)kg/m^(2)vs.(26.58±0.75)kg/m^(2)]、体脂百分比[(36.51±3.76)%vs.(39.21±4.26)%]、腰臀比(0.88±0.04 vs.0.91±0.04)、内脏脂肪等级(10.80±2.45 vs.12.63±2.60)、基础代谢率[(1235.98±74.32)kcal vs.(1254.63±77.23)kcal]明显降低(P<0.05);肥胖干预组体重[(71.79±9.78)kg vs.(77.18±9.62)kg]、BMI[(29.04±2.96)kg/m^(2)vs.(31.21±2.64)kg/m^(2)]、体脂百分比[(40.47±4.77)%vs.(43.97±3.81)%]、腰臀比(0.92±0.05 vs.0.96±0.06)、内脏脂肪等级(14.00±3.74 vs.16.59±3.15)明显降低(P<0.05)。与超重对照组比较,超重干预组移植胚胎数[(1.85±0.36)个vs.(1.96±0.19)个]更少(P<0.05),且活胎数[(0.61±0.37)个vs.(0.56±0.36)个]更多,活产率(43.48%vs.40.00%)更高,但差异无统计学意义(P>0.05)。与肥胖对照组比较,肥胖干预组临床妊娠率(72.41%vs.51.35%)、活产率(58.62%vs.35.14%)更高,但差异无统计学意义(P>0.05)。结论CRD联合肠道微生态制剂可降低超重/肥胖不孕患者的体重和体脂,可能有助于提高肥胖不孕患者辅助生殖成功率。

去乙酰化酶SIRT1的研究进展

去乙酰化酶Sir2基因家族对细胞的生存、凋亡、衰老等生理活动起着十分重要的调节作用,可能是所有生物共同的寿命控制基因之一。去乙酰化酶(SIRT1)是SIR2的同源物,以许多非组蛋白和组蛋白为底物,与代谢综合征、基因稳定性、肿瘤,神经退行性疾病的发生相关。能量限制可通过增加SIRT1活性来延长啮鼠动物的寿命。因此,SIRT1可作为治疗不同疾病的靶点逐渐被人们所重视。

热量限制通过AMPK-SIRT1-线粒体通路延缓小鼠骨骼肌衰老

目的观察热量限制对老化进程中小鼠骨骼肌线粒体等生物学性状的影响,探讨热量限制生物效应的分子机制。方法 13月龄C57BL/6雄性小鼠30只,按照简单随机抽样法分为自由进食组和热量限制组,每周按照自由进食组前1周平均摄食量的60%饲养热量限制小鼠。热量限制12周后,测量骨骼肌衰减指数、胫前肌等肌纤维密度及相对横截面积,透射电镜观察骨骼肌线粒体变化,Western blot检测PGC1α、AMPKα、p-AMPKα及SIRT1等的表达,并比较老年鼠与成年鼠的表达差异。结果 1与自由进食组比较,热量限制组骨骼肌衰减指数变化不明显,胫前肌等肌纤维密度显著升高(P<0.01),相对横截面积降低(P<0.01);2电镜观察显示:与自由进食组比较,热量限制组骨骼肌线粒体长度和宽度均增加(P<0.05,P<0.01),相对密度增加(P<0.01),PGC1α表达升高(P<0.05);3与自由进食组比较,热量限制组骨骼肌AMPK的磷酸化水平升高(P<0.01),同时SIRT1表达也升高(P<0.05);4与成年鼠比较,老年鼠骨骼肌AMPK磷酸化水平下降(P<0.05),SIRT1和PGC1α的表达也均下降(P<0.05)。结论热量限制能显著促进老化进程中骨骼肌线粒体的生成及活性,这一作用可能通过激活AMPK信号途径实现。

苓桂术甘汤联合热量限摄对胰岛素抵抗模型大鼠的影响及机制研究

目的探讨苓桂术甘汤联合热量限摄对胰岛素抵抗(insulin resistance,IR)模型大鼠空腹血糖(FPG)、IR及过氧化物酶体增殖物激活受体-γ(peroxisome proliferator-activated receptor gamma,PPAR-γ)的影响。方法 48只雄性Wistar大鼠随机分为对照组、模型组、限摄组和中药限摄组,每组12只。对照组喂以普通饲料,其他3组以高脂饮食喂养12周建立IR模型。造模成功后,对照组和模型组继续原饲料喂养4天,并灌胃生理盐水20mL/(kg·d);限摄组给予热量限摄4天及生理盐水20mL/(kg·d)灌胃;中药限摄组给予热量限摄4天联合苓桂术甘汤20mL/(kg·d)灌胃。比较各组大鼠体重、FPG、血清空腹胰岛素(FINS)、胰岛素抵抗指数(IRI)和大网膜脂肪组织PPAR-γ蛋白表达。结果热量限摄4天后,与模型组比较,限摄组和中药限摄组大鼠体重明显下降(P<0.01),两限摄组间比较,差异无统计学意义(P>0.05);限摄组大鼠FINS、IRI明显降低(P<0.01,P<0.05),中药限摄组大鼠FPG、FINS和IRI均显著降低(P<0.05,P<0.01);两限摄组大鼠PPAR-γ蛋白表达均明显下降(P<0.01),痰湿状态均得到改善,以中药限摄组作用更显著。结论苓桂术甘汤联合热量限摄能降低IR模型大鼠体重、FPG及IRI,且较单纯热量限摄效果更佳,其改善IR作用可能与抑制PPAR-γ的活性有关,并可能同时具有抑制脂肪细胞分化的作用。

限食8周对大鼠不同类型骨骼肌收缩功能及线粒体生物合成的影响

目的:探讨限食对不同类型骨骼肌收缩功能和线粒体生物合成的影响,为阐明限食的有益作用及机制提供实验依据。方法:每天按正常大鼠摄食量的60%饲养动物以制备限食8周大鼠模型,麻醉下分离比目鱼肌和趾长伸肌,记录电刺激诱导骨骼肌单次、强直和疲劳收缩,观测线粒体基因细胞色素C氧化酶I亚基(COX I)和核基因β-actin拷贝数的比值以反映线粒体生物合成,检测骨骼肌ATP含量以反映线粒体功能。结果:限食8周对电刺激诱导的比目鱼肌和趾长伸肌的单次和强直收缩均有增强作用,但仅提高比目鱼肌的抗疲劳作用;限食也增加两种肌肉的ATP含量,但对比目鱼肌更明显;限食虽对2种肌肉腺苷酸活化蛋白激酶(AMPK)的磷酸化具有增加作用,但只上调比目鱼肌内线粒体生物合成及其调节基因PGC-1α和NRF的转录。结论:限食8周增强大鼠比目鱼肌和趾长伸肌对电刺激的收缩反应,尤其对富含氧化型肌纤维的比目鱼肌更明显;其机制除与限食促进这2种肌肉AMPK活化、增加ATP供应以外,还与上调比目鱼肌线粒体生物合成及其调控因子有关。

限制能量摄入对大鼠体重及空腹血糖、血脂影响

目的探讨限制能量摄入对大鼠体重及其体内空腹血糖、血脂的影响。方法按体重随机将36只雄性Wistar大鼠分为基础组、限能1组和限能2组,单笼喂养12周,检测在自由摄食、80%和60%限能水平下大鼠体重及其空腹血糖、血脂的变化。结果2个限能组体重、脂肪湿重、脂体比、甘油三酯(TG)水平均显著低于基础组(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平显著高于基础组(P<0.05),空腹血糖水平与基础组比较差异无统计学意义,限能2组在实验结束时总胆固醇(TC)水平显著高于基础组(P<0.05)。结论限能可以增高大鼠HDL-C水平,降低TG水平,对空腹血糖无明显的影响,限制能量摄入达到一定程度可升高TC水平。