Differential effects of protein malnutrition and ascorbic acid deficiency on histidine metabolism in the brains of infant nonhuman primates

Abstract: Male infant nonhuman primates (M. nemes-trina) born in captivity were used in the study. They were divided into three groups. The first group of three animals was fed a 20% casein diet and the second group of six monkeys received a 2.0% casein diet. The third group of four monkeys received a 20% casein diet totally devoid of ascorbic acid for 3.5 weeks before the diet was supplemented with ascorbic acid (20 mg/kg diet). All the diets were given to the animals in two daily rations of 100 g/animal. The monkeys fed a 2% casein diet failed to grow, and after about 3.5 months showed variable degrees of edema, hypoalbuminemia, evidence of psychomotor disturbance, depressed plasma levels of many essential amino acids, and other features consistent with the diagnosis of protein-energy malnutrition. Examination of the brains revealed significant alterations in the levels of histidine (+ 172%) and homocarnosine (+ 146%) in comparison with the control well-fed monkeys. Associated with the increase in brain histidine was a marked elevation of brain histamine level. Protein deficiency also led to poor brain retention of ascorbic acid but not to the same degree observed in the ascorbic acid-deficient animals. The latter group of animals, after receiving their diet for about 8 months, demonstrated a modest elevation in the plasma levels of most amino acids in comparison with controls. Ascorbic acid deficiency elicited a significant reduction (p < 0.01) in brain level of histidine, with hardly any change in homocarnosine level. In addition, vitamin C deficiency produced elevation of brain histamine level comparable to findings in the protein-energy-deficient monkeys. The results suggested that protein deficiency raised brain histamine level mainly through increased availability of the precursor amino acid histidine, while defective degradation might account for the increased brain level of this amine in ascorbic acid-deficient monkeys. Histamine has been proposed to have a predominantly depressant action on relevant neurons, and has also been shown to participate with other neuro-transmitters in influencing the function of the pituitary gland by regulating release of the hypothalamic hormones into the portal vessels. The relevance of the findings of marked increases in brain histamine in experimental protein and ascorbic acid deficiencies to the behavioral and extensive endocrinological alterations seen in human malnutrition deserves some intensive investigation.     

Soy isoflavones, diet and physical exercise modify serum cytokines in healthy obese postmenopausal women

Objectives

Evaluate the effect of diet, physical exercise, and a daily oral intake of a soy isoflavones extract (Fisiogen^®) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) on leptin and other adipokines plasma levels in healthy obese postmenopausal women.

Methods

A multicentric randomized longitudinal prospective cohort study was conducted in a sample of 87 healthy obese postmenopausal women. Patients were randomly assigned to a 1200 kcal diet and exercise group (control group) or a group of 1200 kcal diet, exercise, and daily oral intake of daily oral intake of a soy isoflavones extract (Fisiogen^®) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) (soy isoflavones group) along 6 months. Main outcome measures were: anthropometric measures, body composition, leptin, adiponectin, TNF-alpha, homocysteine, C-reactive protein, glucose, insulin, lipid profile and oestradiol serum levels, Kupperman index and Cervantes Scale.

Results

Mean serum leptin and TNF-alpha levels declined after 6 months in both groups of the study, but only women in the soy isoflavones group showed a significant increase of mean serum levels of adiponectin.

Conclusions

Diet, physical exercise and daily oral intake of a soy isoflavones extract (Fisiogen^®) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) have a beneficial effect on serum leptin, adiponectin and TNF-α in healthy obese postmenopausal women after 6 months of treatment.     

Effect of 17α-methyl testosterone incorporated diets on growth of spotted snakehead,Channa punctatus and white carp,Cirrhinus mrigala

The effect of different concentrations of 17α-methyl testosterone incorporated diet on growth performance in the fry of Channa punctatus and Cirrhinus mrigala was evaluated. Four different doses of hormone such as 60, 80, 100 and 120?mg/kg in C. punctatus and 40, 60, 80 and 100?mg/kg in C. mrigala were administered through diet for a period of 90?days.Fifth group on a hormone free diet served as a control. The growth performance in terms of length and weight gain of the fry receiving 100?mg/kg in C. punctatus and 60?mg/kg in C. mrigala were significantly higher than those receiving 80, 120 and 0 (untreated control) mg hormone per kg feed. The highest specific growth rate (0.864?±?1.18%WG d^?1) at 100?mg/Kg diet and (2.47?±?1.26%WG d^?1) at 60?mg/kg diet were observed in C. punctatus and C. mrigala respectively, showing positive influence of hormone incorporated diet on the growth performance. However, the survival rate of both the species remained unaffected by different dosages of 17α-methyl testosterone.     

The stability of Streptococcus mutans populations in the dental plaque of monkeys (Macaca fascicularis)

The Streptococcus mutans populations in the dental plaque of two groups of monkeys were examined. In the first group of 17 monkeys the proportion of Strep. mutans in the dental plaque increased when the monkeys were fed a cariogenic high sucrose (CHS) diet. The same predominant Strep. mutans serotypes were present in the plaque of these monkeys 12 and 25 months after the change to the CHS diet. A second group of 22 monkeys was caged in two communes. As a result of a change to the CHS diet one commune harboured a plaque flora in which Strep. mutans serotype e strains predominated and the second commune harboured a plaque flora in which Strep. mutans serotypes c and h predominated. On the basis of the results from these 39 monkeys three types of Strep. mutans populations were identified: (i) serotype e dominated; (ii) serotype c dominated; and (iii) serotypes c and h in varying proportions. It was not possible to predict which Strep. mutans population would become established in a given group of monkeys. Attempts to demonstrate transmission of Strep. mutans serotypes between pairs and larger groups of monkeys caged together were not successful over periods of up to 36 weeks. The implications of these observations on the use of monkeys as a model of human dental caries is discussed.     

Comparison of rapamycin schedules in mice on high-fat diet

At a wide range of doses, rapamycin extends life span in mice. It was shown that intraperitoneal injections (i.p.) of rapamycin prevent weight gain in mice on high-fat diet (HFD). We further investigated the effect of rapamycin on weight gain in female C57BL/6 mice on HFD started at the age of 7.5 months. By the age of 16 and 23 months, mice on HFD weighed significantly more (52 vs 33 g; p = 0.0001 and 70 vs 38 g; p < 0.0001, respectively) than mice on low fat diet (LFD). The i.p. administration of 1.5 mg/kg rapamycin, 3 times a week every other week, completely prevented weight gain, whereas administration of rapamycin by oral gavash did not. Rapamycin given in the drinking water slightly decreased weight gain by the age of 23 months. In addition, metabolic parameters were evaluated at the age of 16 and 23 months, 6 and 13 days after last rapamycin administration, respectively. Plasma leptin levels strongly correlated with body weight, (P < 0.0001, r=0.86), suggesting that the difference in weight was due to fat tissue mass. Levels of insulin, glucose, triglycerides and IGF1 were not statistically different in all groups, indicating that these courses of rapamycin treatment did not impair metabolic parameters at least after rapamycin discontinuation. Despite rapamycin discontinuation, cardiac levels of phospho-S6 and pAKT(S473) were low in the i.p.-treated group. This continuous effect of rapamycin can be explained by prevention of obesity in the i.p. group. We conclude that intermittent i.p. administration of rapamycin prevents weight gain without causing gross metabolic abnormalities. Intermittent gavash administration minimally affected weight gain. Potential clinical applications are discussed.     

Oral nicotine impairs clearance of plasma low density lipoproteins

The effect of chronic oral nicotine intake on plasma low density lipoprotein (LDL) clearance, lipid transfer protein, and lecithin:cholesterol acyltransferase (LCAT) was examined in male atherosclerosis susceptible squirrel monkeys. Eighteen yearling primates were divided into two groups: 1) Controls fed isocaloric liquid diet; and 2) Nicotine monkeys given liquid diet supplemented with nicotine at 6 mg/kg body wt/day for a two-year period. Averaged over 24 months of treatment, animals in the Nicotine group had significantly higher levels of plasma and LDL cholesterol compared to Controls while plasma LCAT activity was similar for both groups. Following simultaneous injection of 3H LDL and 14C high density lipoprotein (HDL) cholesteryl ester (CE), removal of the latter was not altered by oral nicotine while plasma clearance of 3H LDL was dramatically delayed in Nicotine monkeys. Transfer of 14C HDL CE to very low density lipoprotein (VLDL)-LDL particles was greatly accelerated in the Nicotine group vs Controls while the reciprocal movement of 3H LDL CE to HDL was only higher in experimental animals at two time points following injection of the isotopes. Results from this study provide evidence that one major detrimental effect of long-term oral nicotine use is an increase in the circulating pool of atherogenic LDL which is due to: 1) accelerated transfer of lipid from HDL; and 2) impaired clearance of LDL from the plasma compartment. Diminished removal of LDL is of particular importance because an extended residence time of these particles in circulation would increase the likelihood of their deposition in the arterial wall.     

三聚氰胺等物质给予幼年恒河猴的毒性试验

目的观察三聚氰胺及其同系物给予动物后,导致肾脏损伤、形成结石的过程,及肾脏损伤的恢复过程。方法选择6月龄恒河猴6只,雌雄各半,随机分为3组,2只/组,分别为T1（140 mg/kg三聚氰胺和14 mg/kg三聚氰酸）,T2（140 mg/kg三聚氰胺和50mg/kg腺嘌呤）和T3组（140mg/kg三聚氰胺）。连续70 d口服受试物,观察动物的一般状态,分别于不同时间点进行血液学、血生化、尿常规和肾脏B超的检测;并连续观察18个月,观察动物的生长发育情况。结果 1.各剂量组动物在给予受试物8周后所有动物肾脏中均出现多个结石;停止给予受试物后,所有动物结石数量和大小均呈下降趋势,至停止给予受试物16个月后,全部动物肾脏均未检测出结石。2.各剂量组,血清中β2微球蛋白（β2-MG）和尿酸（UA）等指标随着给药时间的延长而有所增高,但在正常范围内。在动物的恢复期,此两项指标的数值明显下降。结论 1.单纯三聚氰胺（相当于人体使用量48 mg/kg.w.d）不能造成恒河猴肾脏功能的明显损害,可形成肾结石。2.在三聚氰酸或腺嘌呤存在的情况下,三聚氰胺可以造成恒河猴肾功能指标β2-MG和UA在正常范围内升高,并可在肾脏形成结石;。3.经过16个月的恢复所有动物结石无法检出,其中三聚氰胺组动物恢复最快。     

Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet

Oxidative stress contributes to cardiovascular diseases. We aimed to study the effects of palm tocotrienol-rich fraction (TRF) on plasma homocysteine and cardiac oxidative stress in rats fed with a high-methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control. Groups 2–6 were fed 1 % methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60 and 150 mg/kg diet) was added into the diet of groups 3, 4, 5 and 6. The rats were then killed. Palm TRF at 150 mg/kg and folate supplementation prevented the increase in plasma total homocysteine (4.14?±?0.33 and 4.30?±?0.26 vs 5.49?±?0.25 mmol/L, p?<?0.05) induced by a high-methionine diet. The increased heart thiobarbituric acid reactive substance in rats fed with high-methionine diet was also prevented by the supplementations of palm TRF (60 and 150 mg/kg) and folate. The high-methionine group had a lower glutathione peroxidase activity (49?±?3 vs 69?±?4 pmol/mg protein/min) than the control group. This reduction was reversed by palm TRF at 60 and 150 mg/kg diet (p?<?0.05), but not by folate. Catalase and superoxide dismutase activities were unaffected by both methionine and vitamin supplementations. In conclusion, palm TRF was comparable to folate in reducing high-methionine diet-induced hyperhomocysteinemia and oxidative stress in the rats’ hearts. However, palm TRF was more effective than folate in preserving the heart glutathione peroxidase enzyme activity.     

Lippia gracilis Schauer essential oil as a growth promoter for Japanese quail

The use of antibiotics as performance enhancers in animal feeding is declining, so Lippia gracilis Schauer essential oil (LGSEO) could be used as a potential substitute for the conventionally used growth promoters. The LGSEO contains components such as carvacrol and thymol, which kill and/or control pathogenic bacteria, increase population of beneficial organisms, act against oxidative processes and onto nutrient digestibility and absorption. The aim of this study was to investigate the action and the effects of LGSEO as a growth promoter in the diet of Japanese quail by examining their productive performance, intestinal microbiology, blood biochemical parameters, hepatic thiobarbituric acid reactive substances (TBARS) content and intestinal gene expression. A total of 252 two-day-old quail (Coturnix coturnix japonica) were assigned to 3 treatments in 7 replicates, using 12 birds per experimental unit. The treatments consisted of a basal diet, basal diet + LGSEO at 400 mg/kg of diet and basal diet + chemical antimicrobial (bacitracin methylene disalicylate) at 500 mg/kg of diet. The experimental period was 34 days. The highest feed intake (P < 0.01) was found in the group receiving the conventional antimicrobial, whereas the best feed conversion (P < 0.01) was shown by the animals receiving LGSEO. Escherichia coli growth was restricted in the quail receiving the growth promoters. Salmonella spp. growth was controlled by the treatment containing the conventional antimicrobial. There was no difference between the treatments (P > 0.05) for the concentration of aspartate aminotransferase and alanine aminotransferase enzymes in the blood or hepatic TBARS content. Birds receiving negative-control treatment exhibited a higher expression of sodium-glucose cotransporter (SGLT1), while those receiving the treatment with essential oil showed lower catalase (CAT) and glutathione peroxidase (GPX7) expressions compared to the conventional antimicrobial and control groups, respectively. Lippia gracilis Schauer essential oil is a powerful performance enhancer for Japanese quail by virtue of its abilities to improve their intestinal environment, balance the microbial population and reduce energy expenditure for oxidative processes.     

Linseed plus nitrate in the diet for fattening bulls: effects on methane emission,animal health and residues in offal

The combination of linseed and nitrate is known to decrease enteric methane emission in dairy cows but few studies have been carried out in fattening cattle for animal liveweight gain, enteric methane emission, animal health and presence of residues in beef products. To address this gap, 16 young bulls received a control (C) diet between weaning at 9 months and 14 months, then were split into two groups of eight balanced on feed intake, BW gain and methane emission to receive either the C diet or a diet moderately supplemented with extruded linseed and calcium nitrate (LN) for 2 months before being slaughtered. On a dry matter (DM) basis, the C diet contained 70% baled grass silage and 30% concentrate mainly made of maize, wheat and rapeseed meal. In the LN diet, rapeseed meal and a fraction of cereals were replaced by 35% extruded linseed and 6% calcium nitrate; linseed fatty acids and nitrate supply in the LN diet were 1.9% and 1.0%, respectively. Methane emission was measured continuously using the GreenFeed system. Methaemoglobin was determined every week in peripheral blood from bulls receiving the LN diet. Nitrate and nitrite concentrations were determined in rumen, liver and tongue sampled at slaughter. Dry matter intake tended to be lower for LN diet (P=0.10). Body weight gain was lower for LN diet (P=0.01; 1.60 and 1.26 kg/day for C and LN diet, respectively). Daily methane emission was 9% lower (P<0.001) for LN than C diet (249 and 271 g/day, respectively) but methane yield did not differ between diets (24.1 and 23.2 g/kg DM intake for C and LN diet, respectively, P=0.34). Methaemoglobin was under the limit of detection (<2% of total haemoglobin) for most animals and was always lower than 5.6%, suggesting an absence of risk to animal health. Nitrite and nitrate concentrations in offal did not differ between C and LN diets. In conclusion, a moderate supply of linseed and nitrate in bull feed failed to decrease enteric methane yield and impaired bull liveweight gain but without adverse effects for animal health and food safety.     

秦岭南坡川金丝猴的食物组成及季节性变化

2013年3月至2014年2月,在秦岭南坡观音山自然保护区大坪峪颜家沟内选取一群半野生川金丝猴的成年个体作为研究对象,采用瞬时扫描取样法收集其觅食的食物类型数据,目的是为该猴群建立食谱,并通过对比不同季节内觅取的食物组成差异探讨秦岭南坡川金丝猴如何应对喜食食物的季节性缺乏。结果表明：秦岭南坡川金丝猴共采食53种植物（包括34种乔木、13种灌木、6种藤本植物）和4种大型真菌,分别占取食植物组成的64.3%、25.3%、8.0%和2.2%,春、夏、秋、冬季节取食种类和多样性指数分别为20种(3.93)、19种(3.73)、21种(3.87)和25种(4.12)。在秦岭南坡川金丝猴的食物组成中,地衣占总觅食记录的22%;树叶占20%,其中嫩叶9%和成熟叶11%;种子、树皮、芽苞、果实和叶柄分别占16%、15%、11%、 9%和7%。该猴群觅取的植物部位具有明显的季节性差异。春季,对树皮和芽苞的觅食量较高,分别为28%和25%;夏季,增加了对成熟叶的采食量(29%),而减少了芽苞的觅取量(5%);秋季,以取食种子和果实为主,分别占总觅食的48% 和16%;冬季,地衣的采食量达到最大值（41%）。觅食的食物组成与食物的可获得性呈正相关性(R = 0.984, P < 0.01),这与大多数叶猴的适应策略类似,在喜食食物短缺的冬季,它们选择更多的地衣和树皮为食,同时它们采食的种类和食物多样性也有相应增加。     

Effect of protein calorie malnutrition on in vitro incorporation of (U-C14)-glucose in brain of young rhesus monkeys

Twelve young rhesus monkeys weighing 1.5-2.0 kg were acclimatised for a month in the animal house of the Institute. After acclimatization 6 monkeys were placed on a protein calorie deficient diet and remaining 6 on normal diet. The deficiency state was indicated by reduction in body weight, significant decrease in serum albumin, lack of physical activity and shedding of fur. At this stage, animals of both groups were sacrificed and brains were removed. Cerebrum was separated, blotted on filter paper and weighed. In vitro incorporation of (U-C14)-glucose was done for 2 hr in approximately 300 mg cerebrum. Incorporation of this precursor was determined in cerebrum, lipids, its fractions and proteins in both groups. There was increased incorporation of (U-C14)-glucose into tissue, gangliosides, free fatty acids and esterified cholesterol but no significant change in myelin marker lipids and proteins in PCM group was noticed as compared to age matched controls.     

A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (−0.6%, 95% CI, −1.1% to −0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications.This clinical trial was registered with ClinicalTrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT01713764","term_id":"NCT01713764"}}NCT01713764.     

Effects of atorvastatin on progression-regression of renal injury in hyperlipidemic chickens

Complex interrelationships exist between hyperlipidemia and the progression of renal injury. The aim of this study was to evaluate the impact of high plasma cholesterol and triglyceride levels on renal structure and the effects of atorvastatin on progression-regression of renal injury. One-hundred chickens were divided into five groups: Group A: Standard diet (SD) for 6 months; Group B: Hyperlipidemic diet (HD) for 6 months; Group C: HD for three months and SD during the next 3 months; Group D: HD for 3 months and SD during the next 3 months, when they received oral atorvastatin (3 mg/kg/d); Group E: HD for the whole 6 months, and atorvastatin (3 mg/kg/d) during the last 3 months. Increased alpha-actine immunostaining was found in glomeruli of groups B and C. An important decrease of immunostaining was observed in glomeruli of atorvastatin treated groups. Group D showed the lowest value for presence of lipids, and significant differences were found with respect to the rest of the groups. The glomeruli of group B presented the highest damage grades and those of group D showed the lowest grades and presented significant differences from the rest of the groups. The combination of atorvastatin therapy and proper diet proved to be effective in promoting renal disease regression. However, the study of several parameters indicates that neither only diet nor atorvastatin in the progression group resulted completely effective in decreasing the progression of the disease.     

Vitamin D supplementation restores the blunted muscle protein synthesis response in deficient old rats through an impact on ectopic fat deposition

We investigated the impact of vitamin D deficiency and repletion on muscle anabolism in old rats. Animals were fed a control (1 IU vitamin D₃/g, ctrl, n=20) or a vitamin D-depleted diet (VDD; 0 IU, n=30) for 6 months. A subset was thereafter sacrificed in the control (ctrl6) and depleted groups (VDD6). Remaining control animals were kept for 3 additional months on the same diet (ctrl9), while a part of VDD rats continued on a depleted diet (VDD9) and another part was supplemented with vitamin D (5 IU, VDS9). The ctr16 and VDD6 rats and the ctr19, VDD9 and VDS9 rats were 21 and 24 months old, respectively. Vitamin D status, body weight and composition, muscle strength, weight and lipid content were evaluated. Muscle protein synthesis rate (fractional synthesis rate; FSR) and the activation of controlling pathways were measured. VDD reduced plasma 25(OH)-vitamin D, reaching deficiency (<25 nM), while 25(OH)-vitamin D increased to 118 nM in the VDS group (P<.0001). VDD animals gained weight (P<.05) with no corresponding changes in lean mass or muscle strength. Weight gain was associated with an increase in fat mass (+63%, P<.05), intramyocellular lipids (+75%, P<.05) and a trend toward a decreased plantaris weight (−19%, P=.12). Muscle FSR decreased by 40% in the VDD group (P<.001), but was restored by vitamin D supplementation (+70%, P<.0001). Such changes were linked to an over-phosphorylation of eIF2α. In conclusion, vitamin D deficiency in old rats increases adiposity and leads to reduced muscle protein synthesis through activation of eIF2α. These disorders are restored by vitamin D supplementation.     

Preliminary observations, at the ultrastructural level, on the reactivity of cerebral arteries from New Zealand rabbits to combined atherogenic stimuli (hypercholesterol diet and hypertension)

Both in monkeys (Rhesus and Cynomolgus) and in New Zealand rabbits fed an atherogenic diet, a marked delay in the appearance of atherosclerotic lesions of the cerebral arteries in comparison with other arterial districts has been observed. This appearance has been described in monkeys as relatively earlier if hypertension is added to the atherogenic diet. Preliminary observations on a little group of rabbits on a 3 months hypercholesterolic diet, subjected to Goldblatt aortic coarctation, have shown an increase of blood pressure and a severe gross atherosclerotic involvement of aorta, resembling the one obtainable after 6 months of atherogenic diet. Histologically, the aorta predominantly shows lesions of the fatty streaks type with necrotic areas in the deep; the carotid lesions show some lipid in smooth muscle cells disseminated in a sub-endothelial "edematous" space (rich in protein). The cerebral arteries do not show any lesion. At TEM, the aortic lesions look sometimes as advanced plaques with an initial fibrosis at the surface; the carotid lesions are characterized by a granular deposit in the sub-endothelial space in which some smooth muscle cells (with lipid in the cytoplasm) are present; in the cerebral arteries only the presence of collagen fibers among the smooth muscle cells of the media, never observed in the animals fed the atherogenic diet alone, has sometimes been noted.     

Reducing saturated fat intake lowers LDL-C but increases Lp(a) levels in African Americans: the GET-READI feeding trial

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA’s role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants’ mean age was 35 years, 70% were women, the mean BMI was 28 kg/m², and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: −12 mg/dl) as were total cholesterol (−16 mg/dl), HDL-C (−5 mg/dl), apoA-1 (−9 mg/dl) and apoB-100 (−5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.     

Dietary influences on growth and sexual maturation in premenarchial rhesus monkeys

The effect of a high-fat diet on growth, sexual maturation, and developmental changes in serum levels of estradiol (E2), growth hormone (GH), somatomedin-C (Sm-C), and insulin were examined in outdoor-housed premenarchial rhesus monkeys. From 16 to 32 months of age, females were fed either a high-fat diet (HFD, N = 5) with 31% calories from fat or a control diet (commercial laboratory chow, N = 10) with 12% of the calories from fat. Maintenance on a HFD did not accelerate physical growth, as all animals exhibited similar increments in body weight, crown-rump length, and weight/height ratios. In contrast, the HFD group exhibited an earlier onset of perineal swelling and menarche despite lower body weights during that time. Moreover, 80% of the HFD animals exhibited an early first ovulation (31-32 months of age) compared with 40% of control animals. These reproductive changes were associated with significant differences in the endocrine profiles of HFD animals. Fasting serum levels of insulin were significantly elevated within 2 months of diet treatment and remained elevated throughout the study period. Levels of Sm-C were elevated relative to those of controls after 3 months of diet treatment, but not thereafter. Serum GH increased after 6 months on the HFD and, overall, concentrations were higher in HFD animals. A significant rise in E2 was observed after only 45 days on the HFD treatment. These concentrations did not differ from 18 to 21 months of age but again were elevated at 27 months in the HFD females. Since these endocrine and physical changes associated with reproductive physiology occurred in the absence of enhanced growth, these data suggest that a high-fat diet may influence the rate of sexual maturation through changes in certain metabolic factors which may act on the developing neuroendocrine system.     

Cardiac Sympathetic Denervation in 6-OHDA-Treated Nonhuman Primates

Cardiac sympathetic neurodegeneration and dysautonomia affect patients with sporadic and familial Parkinson''s disease (PD) and are currently proposed as prodromal signs of PD. We have recently developed a nonhuman primate model of cardiac dysautonomia by iv 6-hydroxydopamine (6-OHDA). Our in vivo findings included decreased cardiac uptake of a sympathetic radioligand and circulating catecholamines; here we report the postmortem characterization of the model. Ten adult rhesus monkeys (5–17 yrs old) were used in this study. Five animals received 6-OHDA (50 mg/kg iv) and five were age-matched controls. Three months post-neurotoxin the animals were euthanized; hearts and adrenal glands were processed for immunohistochemistry. Quantification of immunoreactivity (ir) of stainings was performed by an investigator blind to the treatment group using NIH ImageJ software (for cardiac bundles and adrenals, area above threshold and optical density) and MBF StereoInvestigator (for cardiac fibers, area fraction fractionator probe). Sympathetic cardiac nerve bundle analysis and fiber area density showed a significant reduction in global cardiac tyrosine hydroxylase-ir (TH; catecholaminergic marker) in 6-OHDA animals compared to controls. Quantification of protein gene protein 9.5 (pan-neuronal marker) positive cardiac fibers showed a significant deficit in 6-OHDA monkeys compared to controls and correlated with TH-ir fiber area. Semi-quantitative evaluation of human leukocyte antigen-ir (inflammatory marker) and nitrotyrosine-ir (oxidative stress marker) did not show significant changes 3 months post-neurotoxin. Cardiac nerve bundle α-synuclein-ir (presynaptic protein) was reduced (trend) in 6-OHDA treated monkeys; insoluble proteinase-K resistant α-synuclein (typical of PD pathology) was not observed. In the adrenal medulla, 6-OHDA monkeys had significantly reduced TH-ir and aminoacid decarboxylase-ir. Our results confirm that systemic 6-OHDA dosing to nonhuman primates induces cardiac sympathetic neurodegeneration and loss of catecholaminergic enzymes in the adrenal medulla, and suggests that this model can be used as a platform to evaluate disease-modifying strategies aiming to induce peripheral neuroprotection.     

Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet

The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat Western diet. To test the hypothesis that a high-fat diet (HFD) promotes colonic aberrant crypt (AC) formation in a manner associated with gut bacterial dysbiosis, we examined the susceptibility to azoxymethane (AOM)-induced colonic AC and microbiome composition in C57/BL6 mice fed a modified AIN93G diet (AIN, 16% fat, energy) or an HFD (45% fat, energy) for 14 weeks. Mice receiving the HFD exhibited increased plasma leptin, body weight, body fat composition and inflammatory cell infiltration in the ileum compared with those in the AIN group. Consistent with the gut inflammatory phenotype, we observed an increase in colonic AC, plasma interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1 and inducible nitric oxide synthase in the ileum of the HFD-AOM group compared with the AIN-AOM group. Although the HFD and AIN groups did not differ in bacterial species number, the HFD and AIN diets resulted in different bacterial community structures in the colon. The abundance of certain short-chain fatty acid (SCFA) producing bacteria (e.g., Barnesiella) and fecal SCFA (e.g., acetic acid) content were lower in the HFD-AOM group compared with the AIN and AIN-AOM groups. Furthermore, we identified a high abundance of Anaeroplasma bacteria, an opportunistic pathogen in the HFD-AOM group. Collectively, we demonstrate that an HFD promotes AC formation concurrent with an increase of opportunistic pathogenic bacteria in the colon of C57BL/6 mice.