太子参多糖减轻高脂诱导的小鼠肝脏胰岛素抵抗

目的:通过研究太子参多糖(Radix Pseudostellariae polysaccharide,RPP)减轻高脂肪诱导肝脏胰岛素抵抗的作用,探寻其主要影响因素及发生的分子机制。方法:随机将C57BL/6J小鼠分为低脂饲料对照组(LFD组)和高脂饲料组(HFD组),16周后,经腹腔注射丙酮酸耐量试验(IPPTT)确定胰岛素抵抗糖代谢紊乱模型成功后,开始进行含RPP(500 mg/kg)的高脂饲料干预(HFD+RPP组),连续干预4周之后,检测丙酮酸耐量以及肝脏组织和线粒体丙二醛(MDA)含量。同时采用Western blot法检测肝脏组织中p-AKT(Ser473/Thr308)、p-AMPK、核因子E2相关因子2(Nrf2)、NQO1和IκBα的蛋白水平变化。结果:经RPP干预后,模型组小鼠血糖水平明显降低;肝脏和线粒体的MDA水平显著降低;肝脏组织p-AKT及p-AMPK的蛋白水平明显增高;NQO1、HO-1和IκBα蛋白水平也同时上调。结论:太子参多糖能够有效抑制高脂肪诱导的C57BL/6J小鼠高血糖作用,其机制可能与改善肝脏胰岛素信号转导,并减轻氧化应激反应,同时激活Nrf2信号通路及抑制肝脏炎症信号激活作用有关。     

GLP-1对非酒精性脂肪肝病大鼠胰岛素抵抗及PKCε的影响

 目的: 探讨胰高血糖素样肽1(GLP-1)对非酒精性脂肪肝病SD大鼠的治疗作用及可能的机制。方法: 32只SPF级雄性SD大鼠(体重约130 g)随机抽取21只予高脂饮食(88%普通饲料+10%猪油+2%胆固醇),余下11只予普通饲料饮食作为空白对照组;12周后,将高脂饮食大鼠随机分为2组,每组10只:高脂组予高脂饮食并腹腔注射等体积的无菌生理盐水,治疗组予高脂饮食并腹腔注射利拉鲁肽(GLP-1类似物)注射液(0.6 mg·kg^-1·d^-1)。治疗4周后处死全部大鼠抽取静脉血并取肝脏组织。全自动生化仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)及葡萄糖(GLU)含量;ELISA法测定血清胰岛素含量。石蜡包埋肝组织做病理切片及HE染色;real-time PCR法测定肝组织蛋白激酶Cε(PKCε)mRNA的表达,Western blot 测定肝组织胞浆PKCε蛋白表达。结果: 与正常对照组相比,高脂组的ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均明显升高;GLP-1治疗组与高脂组相比ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均下降,差异有统计学意义(P<0.05); real-time PCR及Western blot结果提示高脂组PKCε mRNA及蛋白表达减少 (P<0.05);GLP-1治疗组PKCε mRNA及蛋白表达增多(P<0.05)。结论: GLP-1类似物可改善非酒精性脂肪肝的脂质代谢及胰岛素抵抗,该过程可能与PKCε有关。     

茜草水溶性提取物减少高脂饮食诱导的肥胖大鼠内脏脂肪

目的探究传统中药茜草水溶性提取物(RCAE)对高脂饮食诱导的肥胖大鼠体质量、脂肪含量及糖脂代谢指标的影响及机制。方法构建含PPARγ2启动子序列的p GL3-Enhancer-PPARγ2(625 bp)-Luc荧光素酶报告基因表达质粒;建立稳定转染该质粒的3T3-L1前脂肪细胞系;用不同浓度(0.1 mg/L~1 000 mg/L)水提法提取的RCAE作用该细胞或用100 mg/L RCAE作用不同时间,检测PPARγ2启动子活性;用100 mg/L RCAE刺激人脂肪细胞并检测PPARγ2 mRNA表达;同时高脂饮食喂养大鼠,观察小和大剂量RCAE干预对血糖、血脂、胰岛素水平、体质量和内脏脂肪质量等的影响。结果 10 mg/L RCAE能促进3T3-L1细胞荧光素酶的表达,是对照组的1.43倍(P0.01);当浓度达1 000 mg/L时,荧光素酶活性增加至对照组的3.24倍(P0.01)。100 mg/L RCAE刺激3T3-L1细胞28 h,荧光素酶活性达最大值,是对照组的2.72倍(P0.01);还能显著促进人脂肪细胞中PPARγ2 mRNA的表达,是对照组的2.27倍(P0.01)。与高脂对照组相比,小剂量茜草组的空腹胰岛素水平及HOMA-IR显著降低,内脏脂肪质量明显减少(P0.05)。结论小剂量RCAE能显著减轻高脂饮食诱导的肥胖大鼠的内脏脂肪质量和改善胰岛素抵抗。其作用机制可能与增强PPARγ2基因启动子活性和促进PPARγ2 mRNA表达有关。     

Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men

It is currently believed that intramyocellular triglyceride (IMTG) accumulation and insulin resistance are a consequence of dietary fat ingestion and/or the elevated circulating lipid levels associated with chronic fat surplus. The purpose of this study was to compare the effect of short-term starvation versus low-carbohydrate (CHO)/high-fat diet on IMTG accumulation and the development of insulin resistance in physically fit men. Intramyocellular triglyceride content, measured as intramyocellular lipid (IMCL) by proton magnetic resonance spectroscopy (1H-MRS), and glucose tolerance/insulin sensitivity, assessed by frequently sampled intravenous glucose tolerance test (IVGTT), were determined after 67 h of: (a) water-only starvation (S); and (b) very low-CHO/high-fat diet (LC). These diets had in common significant restriction of CHO availability but large differences in fat content. All results were compared with those measured after a mixed CHO diet (C). Dietary interventions were administered by cross-over design. The level of dietary-induced IMTG accumulation (P = 0.46), insulin resistance (P = 0.27) and glucose intolerance (P = 0.29) was not different between S and LC treatments. Intramyocellular triglyceride content and insulin sensitivity were negatively correlated (r = -0.63, P < 0.01). Therefore, whilst insulin resistance may be due to fat accumulation at a cellular level, in the integrated human organism this outcome is not exclusively a function of dietary fat intake. The comparable level of IMTG accumulation and insulin resistance following S and LC may suggest that these metabolic perturbations are largely a consequence of the increased lipolytic response associated with CHO restriction.     

The correlation between insulin resistance and the visceral fat to skeletal muscle ratio in middle-aged women

Central obesity with visceral fat accumulation and the amount of skeletal muscle mass may influence insulin sensitivity via its capacity for glucose load uptake. We investigated the relationships among the following metabolic variables: ratio of fat area to skeletal muscle area (VMR), percent ideal body weight, body mass index, waist-to-hip circumference (WHR) and visceral fat to subcutaneous fat ratio (VSR) in 114 nondiabetic middle-aged women. Anthropometric parameters, lipid profiles and sex hormone- binding globulin were measured. Visceral and subcutaneous fat areas at the umbilical level and the skeletal muscle area at the mid-thigh level were measured and computed. 75-gram OGTT tests were performed, along with measuring plasma glucose, insulin and free fatty acid levels, according to which area under the curve of glucose (Glu-AUC), insulin (Ins-AUC), free fatty acid (FFA-AUC) and glucose/insulin ratio (GIR=Glu- AUC/Ins-AUC), were calculated. 1) Triglyceride was more correlated with VSR than VMR. 2) The independent anthropometric parameters for each metabolic variable were In conclusion, VMR for Ins-AUC, WHR for Glu-AUC and total cholesterol, and VSR for triglyceride. 3) For subjects with higher VMR, age, Ins-AUC and triglyceride were significantly higher. 4) Subjects with higher VMR were older and showed higher Ins-AUC and lower GIR than the subjects with lower VMR. In conclusion, VMR is an anthropometric parameter that reflects insulin resistance concerning glucose metabolism, and VSR is thought to be a good parameter that that reflects the serum lipid levels. Further prospective studies are necessary to reevaluate the visceral fat vs. skeletal muscle relationship.     

增加n-6脂肪酸对高脂诱导的大鼠胰岛素抵抗和血清游离脂肪酸谱的影响

目的探讨喂养占总热量59％的饱和脂肪酸及n-6脂肪酸代替其中20％热量后，对胰岛素抵抗和血清游离脂肪酸谱的影响。方法45只雄性Wistar大鼠分为3组。对照组喂饲普通饲料，高脂组喂饲提供59％热卡的饱和脂肪酸高脂饲料，n-6脂肪酸组喂饲高脂饲料，其中提供20％热量的饱和脂肪酸由豆油中的C18：2代替。各组共喂饲11周后测定糖耐量、空腹胰岛素、胰岛素耐量、胰岛素抵抗指数、血清瘦素、血脂、血清游离脂肪酸谱。结果①高脂组大鼠从第4周开始体重明显升高，糖负荷后血糖、糖耐量试验中葡萄糖曲线下面积、皮下注射胰岛素后血糖及胰岛素耐量试验中葡萄糖曲线下面积、血清胰岛素、胰岛素抵抗指数、血清瘦素、血清胆固醇和甘油三酯含量均较正常对照组明显升高。高脂组大鼠血清游离脂肪酸谱中，饱和脂肪酸及18烷酸明显升高，不饱和脂肪酸及18碳2烯酸、18碳3烯酸、20碳4烯酸、n-6脂肪酸和n-3脂肪酸均明显下降。②n-6脂肪酸组从第1～10周体重均较高脂组明显减轻，糖负荷后血糖和糖耐量试验中葡萄糖曲线下面积、皮下注射胰岛素后40min、90min血糖及胰岛素耐量试验中葡萄糖曲线下面积、血清胰岛素、胰岛素抵抗指数、血清胆固醇、甘油三酯和低密度脂蛋白含量均较高脂组明显降低；血清瘦素水平、高密度脂蛋白、18碳2烯酸较高脂组明显升高。结论n-6脂肪酸代替诱导大鼠胰岛素抵抗的饱和脂肪酸的20％热量后可以降低胰岛素抵抗，同时血清中18碳2烯酸提高。     

Comparison of DNA contents of visceral organs in rats with ventromedial hypothalamic lesions and fed a high fat diet

Bilateral lesions of ventromedial hypothalamus are followed by a number of changes including vagal hyperactivity and hyperinsulinemia. To investigate if cell proliferation occurs in visceral organs in rats with ventromedial hypothalamic (VMH) lesions and fed a high fat diet, we determined DNA contents of visceral organs (liver, pancreas, small and large intestines, spleen, kidney and heart) 1 and 4 week after VMH lesions or start of high fat diet. In rats with VMH lesions, DNA contents increased significantly in liver, pancreas, and small and large intestines at 1 week, and maintained the same levels until the 4th week. DNA contents increased most in the pancreas, followed by small and large intestines, and liver. DNA content did not change in spleen, kidney, or heart. In rats fed a high fat diet, there was no increase in the DNA content of these organs, except in the small intestine at 4 weeks. The results suggest that VMH lesions produce excessive DNA synthesis in visceral organs, whereas a high fat diet does not. VMH lesions may induce cell proliferation in visceral organs through vagal hyperactivity and/or changes of humoral growth factors.     

限食对高脂喂养大鼠肝脏内质网应激的影响

目的：观察限食对高脂喂养大鼠肝脏内质网应激标志伴侣蛋白78 kD糖调节蛋白（GRP78）mRNA表达的影响，以进一步了解饮食控制对肥胖及胰岛素抵抗影响的机制。方法：雄性Wistar大鼠24只，随机分为正常对照组（NC）、高脂饮食组（HF）、热卡限制组（CR），每组8只。NC组和HF组分别给予普通饲料（脂肪热卡比18.94%）和高脂饲料（脂肪热卡比50.55%）喂养12周，自由进食。CR组给予自由高脂饲料8周后，改为半量正常饲料（半量为同龄对照组自由进食量的一半）继续喂养4周。造模结束后检测动物胰岛素抵抗指数（HOMAIR）、内脏脂肪重量/体重比值和血清生化指标变化，光镜和电镜下观察大鼠肝脏组织学改变，RT-PCR半定量检测大鼠肝脏GRP78 mRNA的表达。结果：（1）HF组空腹血胰岛素(FIns) (27.51±3.51) mU/L vs (15.46±2.25) mU/L、甘油三酯（TG）(1.35±0.25) mmol/L vs (0.67±0.10) mmol/L、胆固醇（TC）(2.59±0.34) mmol/L vs (1.41±0.28) mmol/L及胰岛素抵抗指数HOMAIR(5.85±0.23) vs (2.85±0.60)较NC组明显升高(P＜0.01)，且肝脏中脂质沉积明显。（2）限食4周后，CR组的Fins(11.25±2.42) mU/L vs (27.51±3.51) mU/L、TG(0.45±0.06) mmol/L vs (1.35±0.25) mmol/L、TC(1.06±0.15) mmol/L vs (2.59±0.34) mmol/L和HOMAIR(1.91±0.38) vs (5.85±0.23)明显低于HF组(P＜0.01)，同时肝脏中脂质沉积也减轻。（3）电镜下，HF组内质网肿胀断裂，核糖体脱落，糖原溶解，CR组则基本恢复正常。（4）HF组大鼠肝脏中GRP78 mRNA表达明显高于NC组（29.36±3.54 vs 16.51±1.73），而CR组则明显低于HF组（13.70±2.35 vs 29.36±3.54）。结论：合理限制饮食能有效减轻高脂喂养所致的脂质代谢紊乱和胰岛素抵抗，其作用机制至少与肝脏组织中的内质网应激相关蛋白GRP78的mRNA表达受抑有关。     

Trafficking of dietary fat and resistance to obesity

The task of maintaining energy balance involves not only making sure that the number of calories ingested equals the number of calories burned but also involves ensuring nutrient balance. This means that over time, the quantity of carbohydrate, fat and protein consumed equals the amount of each oxidized. While the body has the ability to convert protein to carbohydrate and carbohydrate to fat, over long periods of time the body establishes nutrient balance with a high degree of accuracy storing excess nutrients as fat. To make decisions about food intake, the brain must assimilate information about the quantity of nutrients ingested and their disposition through the body over time. This is a very complex time ordered process as different tissues may be in different states of energy balance at different intervals following food ingestion. The fundamental task for the brain is to assess the influx of nutrients relative to stored pools of those nutrients and the rate at which they are being oxidized. It has been suggested that this task is particularly difficult for dietary fat because the stored pool of lipid is quite large compared to either the stored pools of carbohydrate and protein or the quantity of fat ingested per day. It is clear that some organisms resist weight gain even in the face of highly palatable diets. In fact most individuals eat less on any given day than they could given their maximal capacity for consumption. A central question then is: what restrains food intake in the setting of widely available highly palatable food? In this paper we will discuss the evidence that the movement of dietary fat between tissues may play an important role in the fidelity of nutrient sensing and as a result, resistance or susceptibility to obesity. In particular, the relative metabolism of dietary fat favoring oxidation over storage may be associated with more robust signaling of positive energy balance and resistance to dietary induced obesity in both humans and rats.     

ApoE^-/-母体孕期高脂高胆固醇饮食对子代成年鼠动脉粥样硬化的影响

目的研究母体孕期高脂高胆固醇饮食对子代成年鼠动脉粥样硬化的发生影响。方法ApoE^-/-孕鼠分为高脂高胆固醇饮食组（G组）和普通饮食组（P组）,G组雄性子代成年鼠分为高脂高胆固醇饮食组（G—G）和普通饮食组（G—P）,P组子代雄性成年鼠继续喂养普通饲料（P—P）,60d后检测子代成年鼠总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）浓度,HE染色观察血管形态学变化及动脉粥样硬化（atherosclerosis,AS）斑块形成情况。结果G—G组和G—P组的TC、TG、LDL和HDL浓度较P—P组明显升高,且与P—P组相比Tc浓度存在显著性差异（P〈0．05）,TG、LDL和HDL浓度存在极显著性差异（P〈0．01）;P—P组无AS斑块形成,G—G组与G．P组均有AS斑块形成,前者斑块形成率及斑块面积与血管管腔面积之比（PA／LA）都高于后者,两组PA／LA存在极显著性差异（P〈0．01）。结论母体孕期高脂高胆固醇饮食对子代成年鼠动脉粥样硬化的发生具有重要影响。     

Contribution of visceral obesity to the insulin resistance syndrome.

A high visceral adipose tissue accumulation has been associated with many metabolic perturbations typical of the insulin resistance syndrome, such as dyslipidemia, impaired glucose-insulin homeostasis, hypertension and impaired fibrinolysis. It has been documented that male gender aging, and a hyperglycemic state are conditions that increase the likelihood of displaying features of the insulin resistance syndrome. Accordingly, studies have demonstrated that the variation in visceral adipose tissue accumulation explains a significant proportion of the gender differences in the metabolic risk profile. Age-related differences in metabolic components of the insulin resistance syndrome have also been shown to be partly explained by the concomitant increase in visceral adipose tissue accumulation found with age. Studies have suggested that a high visceral adipose tissue accumulation contributes significantly to the deterioration in the plasma lipid-lipoprotein profile found in hyperglycemic subjects. Finally, it appears that the clustering of metabolic alterations of the insulin resistance syndrome is more pronounced in obese subjects with high levels of visceral fat that in those with a lower visceral adipose tissue accumulation.     

Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling

Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho–dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, ΔFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.     

Effect of dietary magnesium supplementation on bone loss in rats fed a high phosphorus diet.

The purpose of this study was to investigate the effect of dietary magnesium (Mg) supplementation on bone loss in rats fed a high phosphorus (P) diet. Weanling Wistar strain rats were randomly divided into four dietary groups of 6 rats each and fed their respective diets; a diet containing 0.3% P and 0.05% Mg (C), a diet containing 1.5% P and 0.05% Mg (HP), a diet containing 0.3% P and 0.15% Mg (HMg), or a diet containing 1.5% P and 0.15% Mg (HPMg), for 21 days. Compared to the C and HMg groups, serum parathyroid hormone (PTH) concentration was significantly higher in the HP and HPMg groups. Serum osteocalcin concentration and urinary excretion of C-terminal telopeptides of type I collagen (CTx), markers of bone turnover, were significantly higher in the HP and HPMg groups than in the C and HMg groups. Dietary Mg supplementation had no significant effects on serum PTH and osteocalcin concentrations, while urinary excretion of CTx was significantly lower in the HPMg group than in the HP group. These results suggested that dietary Mg supplementation suppressed bone resorption due to high P diet.     

Anti-oxidative effect of apocynin on insulin resistance in high-fat diet mice

The present study examines the effects of apocynin on oxidative stress and antioxidant enzymes in high-fat diet (HFD) induced obese mice. After 12 weeks on HFD, the C57BL/6J mice that clearly exhibited insulin resistance received apocynin (2.4g/L) in their drinking water for five weeks. The results show that apocynin treatment significantly ameliorated hyperglycemia, hyperinsulinemia and dyslipidemia in HFD mice. Furthermore, the intraperitoneal glucose tolerance test (IPGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) indicate significant improvement of insulin sensitivity in HFD mice after apocynin treatment. Compared to the HFD control mice, serum malondialdehyde (MDA) was significantly lower and serum superoxide dismutase (SOD) was significantly higher in apocynin treated HFD mice, indicating that apocynin suppressed systemic oxidative stress in the treated group. In the liver, apocynin significantly reduced the level of MDA. Accordingly, apocynin treatment strengthened the antioxidative defense system with an increased activity of SOD, glutathione-peroxidase (GSHpx) and content of reduced glutathione (GSH). We also found that hepatic catalase (CAT) activity significantly decreased after apocynin treatment which may indicate that apocynin reduces hydrogen peroxide and oxidative stress in the liver. These results suggest that apocynin may ameliorate insulin resistance by reducing systemic and hepatic oxidative stress in HFD fed mice.     

Effect of dietary fat on antibody response and on down-regulation

Diets differing in the ratios of polyunsaturated to saturated fatty acids (P/S) have dramatically different effects on the extent to which pretreatment with aggregate-freed form of a foreign protein augments or diminishes (by sensitization or down-regulation) the subsequent response to an immunogenic form of the same protein. We have examined this phenomenon in terms of both down-regulation (acquired immunological tolerance) and sensitization induced in 87-week-old female C57BL/6 mice. Antibody response in these mice, fed on low P/S diets, could be down-regulated by pretreatment with aggregate-free rabbit gamma globulin, as manifested by antibody to aggregated rabbit gamma globulin of isotypes IgG3 and IgG2b. Animals fed high P/S diets were not down-regulated by the pretreatment, but were sensitized; there was a 2-3-fold increase in IgG3, IgG1, IgG2a and IgA antibody to rabbit gamma globulin.     

高脂饮食导致大鼠肝脏胰岛素抵抗的作用机制研究

目的: 本研究旨在建立SD大鼠胰岛素抵抗模型,观察高脂饲料喂养的SD大鼠肝脏中氧化应激以及胰岛素抵抗的发生,分析胰岛素抵抗状态下活性氧(ROS)的变化,初步探讨ROS的主要来源。方法: 以高脂饲料喂养6只4周龄雄性SD大鼠12周,建立大鼠胰岛素抵抗模型。用优越血糖仪以电子感应法测定血糖,放射免疫法检测血清胰岛素水平。二氢乙啶(DHE)染色观察肝脏组织中的ROS水平。Western blotting检测NADPH氧化酶3(NOX3)的表达。结果: 以高脂饲料喂养12周后,大鼠空腹血糖水平略有上升,但与对照组的大鼠相比无显著差异,而胰岛素敏感指数降低。蒽酮法的检测结果显示高脂饲料喂养大鼠肝组织糖原含量显著降低,高脂饮食大鼠肝组织中NOX3的表达显著增加,DHE染色显示肝组织ROS水平显著增加,提示ROS在肝胰岛素抵抗发生中起重要作用。结论: 高脂饲料喂养SD大鼠胰岛素敏感指数降低,肝组织中NOX3表达和ROS水平显著增加,糖原含量显著降低。     

Effect of high fat diet on NKT cell function and NKT cell-mediated regulation of Th1 responses

Diet is one of the important factors that modulate immune responses. In the present study, we have examined the capacity of dietary lipids to modify immune responses in mice and we have investigated the contribution of glycolipid-reactive natural killer T (NKT) cells in this process. Mice fed, high fat diet (HFD; 21.2% fat, 0.20% cholesterol) for 3 weeks, as compared with mice fed standard fat diet (SFD; 4.3% fat, 0.03% cholesterol), showed significantly reduced interferon-γ production in sera at 6 or 12 h after intraperitoneal injection of an NKT cell ligand, α-galactosylceramide. In contrast, production of interleukin-13 was significantly higher at 2 and 6 h in HFD fed mice compared with mice on SFD. No difference was detected in the serum interleukin-4 levels between these two groups of animals. The proportion of NKT cells in spleen and liver was reduced in mice fed HFD compared with those on SFD. In addition, activation of NKT cells assessed by up-regulation of CD69 was suppressed specifically in liver from mice fed HFD. Recall responses of conventional T cells and delayed-type hypersensitivity (Th1 type) against ovalbumin were significantly suppressed in mice fed HFD in comparison with those fed SFD. This suppression was not observed in CD1d^−/− mice, suggesting that NKT cells in mice fed HFD played a role in suppressing Th1 responses. Taken together, our findings suggest a critical link between NKT cells, dietary lipid and adaptive immune responses.     

Experimental atherosclerosis in swine: effect of dietary protein and high fat

Two groups of pigs each consisting of 6 animals were fed for 18 months on isocaloric amounts of an experimental diet with a high fat content and cholesterol but with widely different levels of protein (5% vs. 25% by weight of the diet). In addition, a third group consisting of 4 animals was maintained on normal stock diet to serve as control.Animals of the low protein group showed the maximal intimal surface area involvement with atherosclerotic lesions in the aorta and coronary arteries, and also the most severe among the three groups. No significant differences were noted in the extent and severity of lesions between the high protein-high fat fed animals as compared with the high protein-low fat fed controls. Lesions of the low protein group had a higher cholesterol content and a raised cholesterol:phospholipid ratio than those in the other two groups.Extremely low levels of dietary proteins seem to have had a promotive effect on the induction of atherosclerotic lesions by an atherogenic diet, whereas adequate levels of dietary proteins have had a protective influence. The precise mechanism by which varying levels of dietary proteins have such effects is not understood. It may possibly be related to the aberrations of lipid metabolism induced by extremely low levels of dietary proteins.