bluuebunny/crossref_metadata_2025 huggingface dataset:
Ground squirrels as an animal research model for eating and metabolic disorders
Authors: Maher Margaret A , Kohlnhofer Bridget M , Abboud Christine , Hill Whitney , Benrud Jake , Cooper Scott T
Published: June 2021

Thirteen‐lined ground squirrels (Spermophilus tridecemlineatus) “binge” and stash food leading up to hibernation and “restrict” and ration food during hibernation. This requires a dramatic adaptation to changing environmental conditions. We have studied the transcription of appetite regulating hormone receptors in brains by quantitative PCR, and plasma hormone levels by ELISA, in hibernating and non‐hibernating squirrels. Transcription of ghrelin and leptin receptor genes were suppressed 10‐fold, and plasma leptin and ghrelin levels (n=5/condition) were significantly reduced by 20–25% during hibernation. In contrast, melanocortin and cholecystokinin receptor transcription was elevated during hibernation. Our preliminary studies suggest differential transcriptional regulation and hormone levels of key central (brain) and peripheral (gut and adipose tissue) appetite and metabolism regulatory systems. These differences warrant further investigation and correlation with nutrient intake during different seasonal phases. Moreover, comparison of these regulatory systems in different squirrel states and comparable human dietary conditions (such as binging and restricting) may provide insight for effective points of behavioral, nutritional or pharmaceutical intervention. Funded by University of Wisconsin‐System, WiSys, and NSF‐REU grants.
Pharmacological Dose of alpha‐Tocopherol Induces Cardiotoxicity in Wistar Rats Determined by Echocardiography and Histology
Authors: Ferreira Ana Lucia Anjos , Nascimento Maria Carolina Munhoz Oliveira , Mastubara Beatriz Bojikian , Matsubara Luiz Shiguero , Correa Camila Renata , Pereira Elenize Jamas , Moreira Priscila Lucelia , Carvalho Flavio Augusto , Burini Caio Henrique Paganini , Padovani Carlos Roberto , Yeum Kyung‐Jin
Published: June 2021

The effect of pharmacological dose of alpha‐tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha‐tocopherol, n = 11) group. Animals received corn oil (C) or alpha‐tocopherol dissolved in corn oil [250 mg alpha‐tocopherol/(Kg body wt/day)] (E) by gavage for a 7‐week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac alpha‐tocopherol absorption at the end of study period. As compared to the C group, alpha‐tocopherol supplemented group showed significantly (p<0.05): lower body weight (E, 412.8 g vs C, 480.3 g) and total cardiac weight (E, 0.94 g vs C, 1.08 g); cardiomyocyte histological impairment; smaller left ventricle (LV) (LV end‐diastolic diameter (E, 7.22 mm vs C, 7.37 mm), lower LV systolic [left ventricle fractional shortening (E, 47.6% vs C, 53.6%) and ejection fraction ratio (E, 85.4 vs C, 89.9)] and diastolic [early peak velocities of diastolic transmitral flow (E, 64.6 cm/sec vs C, 75.1 cm/sec)] function. The alpha‐tocopherol uptake in target tissue was confirmed by determination of alpha‐tocopherol concentration medians in cardiac tissue (E, 109.91 nmol/kg vs C, 52.09 nmol/kg). The current study indicates that pharmacological dose of alpha‐tocopherol supplementation can induce cardiotoxicity in healthy rats [Supported by FAPESP 05/52571‐5; USDA1950‐51000‐065‐08S].
High Fat Diet Feeding Impairs Lactogenesis and Butyrophilin Expression in the Mammary Gland of Mice
Authors: Anthony Tracy G , Cundiff Judy K , Lohe Kim , Parsons Cathy , Mather Ian H , Akers R Michael
Published: June 2021

Overfeeding and obesity negatively impacts milk production in animals, but the underlying mechanisms are unknown. To address this, female C57BL/6J mice were assigned at weaning to a low‐fat control diet (LF, 7% by wt), or a high‐fat diet (HF, 35% by wt) for 8 wks then mated. Dams were killed on pregnancy day 14 (P14) or lactation day 1 (L1) and blood, gonadal fat pads and mammary glands were harvested. HF dams had 2–3 fold heavier mammary glands and fat pads as compared to LF dams. HF dams had 2–4 fold higher serum leptin and 25–35% lower serum adiponectin as compared to LF dams. Mammary whole mounts showed less ductal branching and alveolar buds in HF as compared to LF dams. Epithelial content digitally quantified from stained mammary sections confirmed significantly (~50%) less mammary development in HF. LF and HF litter sizes were similar, but the number of viable pups was lower in HF, and those that lived had little to no milk present in the stomach. Cross‐fostering HF litters onto LF dams rescued pups whereas the reverse was not true. Protein expression of adipophilin and butyrophilin increased in LF mammary gland between P14 and L1, while protein expression of perilipin did not. At L1, butyrophilin expression in HF mammary gland was reduced by at least 50% as compared to LF while adipophilin and perilipin expression remained stable. The results suggest that high fat diets hinder lactogenesis by inhibiting mammary gland development and expression of butyrophilin, a protein important for the onset of milk fat globule secretion. Funded by Mead Johnson Nutrition.
Impact of selenate treatment on broccoli glucosinolate profile and bioactivity
Authors: Volker Sonja E , Freeman John , Banuelos Gary , Jeffery Elizabeth H
Published: June 2021

Selenium (Se)‐enriched broccoli has potent anticarcinogenic effects, which are suggested to be the result of changes in detoxification enzyme activity, induction of apoptosis, and inhibition of histone deacetylation (HDAC) and angiogenesis. We previously showed that feeding high‐Se broccoli powder (H‐SeB; 4.28 ppm) to male Copenhagen rats induced hepatic ethoxyresorufin‐O‐deethylase (EROD) and NAD(P)H:quinone oxidoreductase (NQO1) activity 1.6 and 1.9‐fold over low‐Se broccoli (L‐SeB; 0.25 ppm), respectively. To elucidate the relative role of Se in induction of these enzymes, mouse hepatoma Hepa‐1c1c7 cells were exposed to aqueous extracts of H‐SeB or L‐SeB. Extracts of H‐SeB increased EROD and NQO1 activity 2.7 and 1.3‐fold, respectively. Adding Se as selenite or Se‐methylselenocysteine (SeMSC) to L‐SeB extracts had no impact on EROD or QR activity. Likewise, Lee et al. reported that SeMSC up to 2.5 mM had no direct effect on HDAC in prostate cancer cells. Selenium‐enrichment of broccoli increased levels of the glucosinolate neoglucobrassicin, the hydrolysis product of which is known to induce EROD activity. We conclude that the increase in detoxification enzyme activity is not a direct effect of Se, but the result of a (plant) metabolite of Se and/or changes in the glucosinolate profile. Supported by grants from USDA/AFRI and the Illinois Council on Food and Agricultural Research.
Structure‐activity relationships of (1′S)‐acetoxychavicol acetate for the decrease in intracellular glutathione level in Ehrlich ascites tumor cells
Authors: Matusi‐Yuasa Isao , Xu Shenghui , Kojima‐Yuasa Akiko , Azuma Hideki , Kennedy David Opare
Published: June 2021

We examined the structure‐activity relationships of (1′S)‐Acetoxychavicol acetate ((S)‐ACA), an anticarcinogenic compound naturally obtained from the rhizomes and the seeds of the Zingiberaceae plant, for the decrease in intracellular GSH making comparison with the activity of some synthetic‐related compounds in Ehrlich ascites tumor cells. (R)‐ACA and rac‐ACA caused the inhibition of cell viability similarly as (S)‐ACA. In previous study, we have shown that (S)‐ACA caused a rapid decrease in GSH level in less than 15 min after (S)‐ACA exposure. The addition of (R)‐ACA and rac‐ACA also caused the decrease in cellular GSH in Ehrlich ascites tumor cells. (S)‐ACA and (R)‐ACA induced cell death was reversed by the addition of N‐acetlycysteine. Therefore, we examined the inhibitory activities of rac‐ACA and its 9 derivatives toward the viability, the intracellular GSH level and GR activity in the cells was remarkably decreased with the treatment of rac‐ACA, rac‐3,4‐ACA, rac‐2,4‐ACA, rac‐trp‐7c‐ACA and rac‐BCB, but not changed with 20 μM concentration of 3′‐ACA, rac‐m‐ACA, rac‐o‐ACA, rac‐ADC, and rac‐DHACA. We also found that there is a highly significant correlation between GR activities and GSH levels and suggested that the decrease in the intracellular GSH levels was mainly caused by the decrease in the activity of GR in less than 15 min after ACAs exposure in Ehrlich ascites tumor cells.
Hepatoprotective effects of equol through antioxidative and anti‐apoptotic function in 7,12‐Dimetylbenz(a)anthracene‐induced oxidative stress of mice
Authors: Kim Gun Hee , Choi Eun Jeong
Published: June 2021

We investigated the hepatoprotective effects of equol, the major metabolite of the antioxidant phytochemical daidzein, in mice with 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced oxidative stress. Oral pre‐administration of equol to mice who received DMBA intragastrically twice a week for 2 weeks significantly decreased their levels of biomarkers (thiobarbituric acid‐reactive substances, carbonyl content, and serum 8‐hydroxy‐2‐deoxyguanosine) of DMBA‐induced oxidative stress. Although several antioxidant enzymes were down‐regulated in DMBA alone treated mice, pre‐administration of equol blocked much of this effect, increasing catalase and superoxide dismutase activity in a dose‐dependent manner. Although equol did not affect the ratio of oxidized to reduced glutathione, it activated the glutathione peroxidase and glutathione reductase enzymes, and this effect was significant at a dose of 25 mg equol/kg body weight. DMBA treatment induced apoptosis, as shown by a decrease in the Bcl‐2 level and an increase in the levels of Bax, cleaved caspase‐3, and poly(ADP‐ribose) polymerase. These apoptotic effects were also reversed by equol at all doses tested. These results suggest that equol exerts a protective effect on mice with DMBA‐induced oxidative stress by acting as an antioxidant and by reducing apoptosis.
In Vitro Screening of Tumoricidal Properties of International Medicinal Herbs
Authors: Mazzio Elizabeth A , Park Kathleen , Soliman Karam F
Published: June 2021

With growing use of anticancer complementary and alternative medicines (CAMs) worldwide, there is a need to assess, screen and rank commercially available herbal products for relative tumoricidal properties under standard experimental conditions. Moreover, high through‐put screening may provide information on potentially new plant resources for chemotherapy drugs. Previously, we screened and ranked 374 herbal extracts obtained from diverse international natural plants (Phytother Res. 2009 Mar; 23(3):385–98). In the current study, we screened an additional 307 extracts predominantly from plants used in traditional Chinese medicine (0.005–5.0 mg/ml), ranking them according to tumoricidal potency on malignant neuroblastoma. The results in this study show the greatest effects (LC50 < 0.08 mg/ml) for extracts of gromwell root also known as “Hong Tiao Zi Cao” (Lithospermum erythrorhizon root) (LER) < beth root (Trillium Pendulum Root) and Galbanum (Ferula galbaniflua). The reference standard: turmeric (Curcuma longa), a known anti‐tumor herb yielded an LC50 of .269mg/ml displaying 7% the potency of LER. In conclusion, this study shows greatest efficacy for water soluble constituents within gromwell root, which is traditionally used as a Chinese tea.(Supported from NIH grant RR03020)
NG2 Expression in Mammary gland and DMBA‐Induced Tumor of Obese Zucker Rat Model
Authors: Karbassi Behjatolah M , Korourian Soheila , Jo Chan H , Hakkak Reza
Published: June 2021

Recently, we reported that intact obese Zucker rats had increased susceptibility to DMBA‐induced mammary tumors. In the present study, we investigated the expression of neuro‐glial proteoglycan 2 (NG2) in mammary gland and tumor. NG2 is a cell surface chondroitin sulfate proteoglycan that is expressed by tumor and its stroma. NG2 expression is associated with tumorigenesis, tumor progression and invasion. Obese Zucker rats were purchased at age 40 days and were gavaged at age 50 days with 65 mg/kg DMBA. Rats had ad lib access to water and regular chow diet. Rats were weighed and killed 140 days post‐DMBA treatment. Sections of mammary gland and mammary tumors were taken to determine NG2 expression by Real‐time quantitative PCR. We found that NG2 was expressed equally in tumor microenvironment of both tumor bearing and normal animals. Interestingly the NG2 expression increased in Invasive ductal carcinoma (IDC) tumors as compared with ductal carcinoma in situ (DCIS) tumors. In summary, our preliminary data suggest that up‐regulation of this antigen on tumor cells may be correlated with transformation of DCIS to IDC in breast cancer (Supported by ABI to RH).
A legume enriched diet facilitates weight loss and improves biomarkers of insulin resistance and inflammation
Authors: Zhang Zhiying , Lanza Elaine , Mitchell Diane , Mentor‐Marcel Roycelynn , Colburn Nancy , Hartman Terryl
Published: June 2021

The LIFE Study tested the effects of a legume enriched, low‐glycemic index, weight maintenance diet on biomarkers of insulin resistance and inflammation among males at high risk for colorectal cancer (n=64). The study included an optional 4‐wk period (n=44) where men continued on the diet with consistent legume consumption but dietary guidance was provided and weight loss encouraged. Mean body weight and BMI significantly decreased by 4.4% (−4.0±0.4 S.E.M. kg) and 1.3 (±0.1 kg/m2), respectively. Levels of serum total cholesterol (TC), LDL‐C, TG, C‐peptide, and fasting plasma glucose, insulin, and C‐reactive protein were all significantly reduced. Compared to the weight maintenance diet, the weight loss diet was lower energy (−770.3 ± 397.0 S.D. kcal/d) and energy density (0.70 vs 1.15, P<0.001). Subjects consumed less total fat (31 vs 34% energy, P<0.001), saturated fat (10 vs 12%, P=0.007), and cholesterol (62.3 vs 70 mg/1000 kcal/d, P=0.0255). After energy adjustment they ate more vegetables (2.6 vs 2.2 serv./1000 kcal/d, P=0.0133) and legumes (1.9 vs 1.5 serv./1000 kcal/d, P=0.0009) during the weight loss phase, and consumed more total carotenoids (10759 vs 8799 μg/1000 kcal/d, P=0.0014), vitamin C (74.0 vs 61.8 mg/1000 kcal/d, P=0.0202), and folate (559.7 vs 444.1μg/1000 kcal/d, P<0.001). These results indicated that a high legume diet may facilitate weight loss and improve the aforementioned biomarkers.

Grant Funding Source: National Institute of Health
High‐fat diet induced obesity accelerates colon tumor formation in AJ and ICR mice
Authors: Park Shin‐Young , Kim Jong‐Sang , Seo Young‐Rok , Sung Mi‐Kyung
Published: June 2021

Recent studies have indicated that the risk of colorectal cancer is associated with overweight and obesity. The objective of this study was to determine the effect of high fat diet induced obesity on the incidence of AOM/DSS‐induced colon carcinogenesis and to elucidate possible mechanisms. Strain‐specific responses were studied using A/J and ICR mice. Study results indicated the tumor numbers in animals fed high fat diet were significantly higher than those of the animals on low‐fat diet. The concentrations of adipose tissue related serum factors including leptin, insulin and IGF‐1 were elevated in obese animals indicating these are one of the possible signals to facilitate colon tumor formation. The expressions of leptin mRNA in adipose tissue and leptin receptor(ObR) mRNA in colon tissue were significantly higher in obese mice compared to those in lean mice only in AJ stain. The protein expressions of ObR, IR, p‐Akt, p‐ERK, Bcl‐xl and cyclin D1 were higher in obese animals than those in lean animals for both strains. These results imply adipose tissue related hormonal factors contribute to colon tumor growth. Strain‐specific responses are also suggested. This study was supported by the SRC program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (2009‐0063409 and R01‐2008‐000‐20708‐0).

Grant Funding Source: Nutrition(ASN)
Antiobesity effects of Foeniculum Fructus water extracts in high fat diet‐induced obese mice
Authors: Baek Jong Mi , Chung Mi Ja , Kim Dae Jung , Seo Dong Joo , You Jin Kyoun , Kim Tae Hyuk , Choe Myeon
Published: June 2021

Recently, many people induce obesity. Some authorities propose obesity as a serious and growing public health problem. Some studies show that excessive body weight has been shown to predispose to various diseases, for example cardiovascular diseases, diabetes mellitus type 2, and osteoarthritis. Therefore, the therapeutic approach using natural substance has been suggested that they have many benefits more than artificial medicine. Thus, we used Foeniculum Fructus (FN) water extract for this study. FN was used to as a popular remedy and its plants have several bioactive compounds. The purpose of this study was investigated the effects of FN extracts on body weight, adipocytes size, plasma lipid levels and enzyme activity in high fat diet‐induced obese mice. Eleven‐weeks feeding with high fat diet(HFD) resulted in significant increase of lipid levels, body weight, liver and epididymal adipose tissue weights, compared with the HF‐free group. FN significantly reduced plasma total cholesterol, triglyceride and glucose concentrations as well as body weight, liver weight and epididymal adipose tissue weight. The size of adipocytes in HFD group was significantly larger than those of HF‐free group but FN significantly decreased the size of epididymal adipocytes. These results suggest that oral feeding of the FN may have anti‐obesity effects by suppressing body weight gain, adipose tissue formation and adipocyte size increase. (This research was supported by the Ministry of Knowledge Economy through the fostering project of the Human Resource Training Project for Regional Innovation.)
Carbohydrate Intake is Associated with Diet Quality in Patients with Type 2 Diabetes
Authors: Hwang Ji‐Yun , Park Ji Eun , Kim So Jung , Choi Young Ju , Huh Kap Bum , Chang Namsoo , Kim Wha Young
Published: June 2021

Recently, high carbohydrate intake has been reported to be related to low diet quality and risk factors of diabetic complications. Traditionally, Koreans consume high quantities of carbohydrates, mainly from white rice. This study was to examine whether excessively high carbohydrate intake (>65% of energy from carbohydrate) was negatively associated with diet balance and quality in Korean patients with type 2 diabetes. Subjects from an ongoing, prospective study (n=948) were classified according to the percent of energy from carbohydrate intake (4 groups: <55%, 55–59%, 60–64%, and ≥65%). A high carbohydrate diet (≥ 65% of energy) was associated with insulin resistance, hypertension, and dyslipidemia. Most of the nutrient and food group intakes per 1000kcal and diet quality decreased with an increase in the percent of energy from carbohydrates. Excessive carbohydrate intake is related to diabetic complications, which may be through unbalanced and low‐quality diet. Carbohydrate intake that constitutes around 50%–55% of total energy intake and a high‐quality diet with adequate vitamins and minerals that includes protein foods, fruits, and vegetables may be recommended to manage and prevent diabetic complications of patients with type 2 diabetes in populations where white rice is consumed as the main staple food.

This work was supported by the Second stage of BK21 Project in 2008 and Seoul R&BD Program, No. 10526.
Dietary patterns of Korean patients with type 2 diabetes and their relation to risk factors of diabetic complications
Authors: Hwang Ji‐Yun , Lee Yoon Jung , Kim So Jung , Chang Namsoo , Kim Wha Young
Published: June 2021

We characterized dietary patterns and their relation to risk factors of diabetic complications in 901 Korean patients with type 2 diabetes from an ongoing, prospective study. Two dietary patterns were empirically derived by principal component analysis composed of 39 food groups: pork and noodle pattern characterized by high intake of pork, boiled pork, processed fish, noodles, pizza, eggs and beverages and vegetable and legume pattern characterized by high intake of vegetables, legumes, mushrooms, seaweed, tofu, Kimchi, anchovy and low fat dairies. The quality of diet measured by Mini Dietary Assessment was lowest in the highest tertile of pork and noodles pattern scores but highest in the highest tertile of vegetable and legume pattern. The highest tertile of pork and noodle pattern scores had significantly greater triglyceride and C‐peptide levels than the lowest tertile whereas the highest tertile of vegetable and legume pattern had significantly lower levels of triglyceride and insulin compared to the lowest tertile. Moreover, subjects with the highest tertile of pork and noodle pattern had a significantly greater risk of having high waist circumferences (OR=1.59, 95% CI=1.11–2.29), BMI (OR=1.53, 95% CI=1.08–2.17) and diastolic blood pressure (OR=1.56, 95% CI=1.09–2.22) than the lowest tertile. Multiple food groups affect diabetic complication risk beyond that of the individual food groups.

This work was supported by the Second stage of BK21 Project in 2008 and Seoul R&BD Program, No. 10526.
The elevated serum Monocyte Chemoattractant Protein‐1 (MCP‐1) in obesity is influenced by parathyroid hormone (PTH) and not body mass index (BMI)
Authors: SUKUMAR DEEPTHA , PARTRIDGE NICOLA , WANG XIANGBING , SHAPSES SUE
Published: June 2021

Monocyte chemoattractant protein‐1 is an inflammatory cytokine that is produced predominantly by macrophages, endothelial cells and is expressed in adipose tissue, and also by the mature osteoblast. PTH administration increases gene expression and serum MCP‐1 in rodents, yet both MCP‐1 and PTH are elevated in obesity. The goal in this study was to determine whether the higher MCP‐1 in obesity is influenced by PTH. We recruited 84 women aged 51 ± 10 years, who were either normal‐weight (NL‐wt, n = 38, BMI = 22 ± 2 kg/m2) or obese (Ob, n = 46, BMI = 44 ± 7 kg/m2) and further separated them into 2 categories based on median of PTH. BMI, fat mass, lean mass and calcium intake did not differ in the two PTH groups in NL‐wt and Ob women. PTH was inversely associated with serum 25 hydroxy vitamin D levels in the entire population (r = −0.31, p<0.01). Ob and NL‐wt women in the high PTH groups had higher MCP‐1 (p<0.05) and no difference in control adipokines [C‐reactive protein (CRP) and adiponectin]. As expected, CRP was higher and adiponectin was lower (p<0.05) in Ob than NL‐wt women, whereas MCP‐1 did not differ due to weight category. We found that the positive association between MCP‐1 and BMI was only present when PTH was <40 pg/mL (normal = 10–55 pg/mL). Together, these data suggest that when serum PTH is in the high‐normal range, it has a greater influence on MCP‐1 than BMI, as observed in both NL‐wt and Ob women.

Grant Funding Source: CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCES (CCTS)‐ UMDNJ
A high fat diet reduces the expression of lipogenic, lipolytic and oxidative genes in white adipose tissue. The effect of the concentration and type of fatty acid is dependent of the dietary protein
Authors: Diaz‐Villaseñor Andrea , Palacios‐Gonzalez Berenice , Tovar‐Palacio Claudia , Tovar Armando R , Torres Nimbe
Published: June 2021

It has been postulated that not only the quantity, but also the type of dietary fat has important implications in the metabolism of lipids and glucose, therefore in obesity. Fatty acids are important mediators of gene expression of metabolic enzymes in the liver, whereas its role in adipose tissue, also involved in metabolism homeostasis, has been little studied. The present study shows that in white adipose tissue of hyperleptinemic and hyperinsulinemic Zucker fa/fa rats chronically fed 5% polyunsaturated fatty acids (PUFA), the expression of genes involved in lipogenesis (SREBP‐1, ACC, FAS, SCD‐1), fatty acid oxidation (PPARα, CPT‐1, UCP‐1, 2 and 3 and AOX) and glucose homeostasis (AMPKα, LKB1 and GLUT4) was dependent by the type of protein consumed (casein or soy), maintaining in both the functionality of the adipocyte. However, if the amount of fat increased in the diet (10%), the expression of all the measured genes was abated drastically, including the lipolytic ones (HSL and perilipin). Gene expression was dependent of the type of fat consumed (PUFA or saturated fatty acids) as well as of the type of protein. Of the four groups tested with 10% of dietary fat, the least affected was the group fed PUFA with soy protein. The action of the different sort of fatty acids in conjunction with the type of protein as regulators of gene expression in the adipose tissue was independent of insulin and leptin.

Supported by the INCMNSZ
Effect of dietary fatty acids on lipid profile and gene expression in blood, skeletal muscle, adipose, liver and intestine
Authors: Jesch Elliot Denver , Wang Zhigang , Black Paul N , DiRusso Concetta C
Published: June 2021

Lipotoxicity is the phenomenon that occurs when a tissue accumulates excessive amounts of lipid, which can induce a range of events at the cellular level from dysfunction to apoptosis and at the systems level inducing various disease states such as metabolic syndrome or cardiovascular disease. The effects of specific fatty acid classes have been implicated in the progression or protection of humans and animals from type 2 diabetes mellitus, metabolic syndrome and cardiovascular disease. We examined the effect of feeding diets enriched in various fatty acid classes (saturated, poly‐unsaturated, highly‐unsaturated and mixed saturated/highly‐unsaturated) on lipid accumulation, lipid profile and gene expression. Eight, four week old C57BL6 mice were fed one of four AIN‐93G diets enriched with six percent lipid for eight weeks. After eight weeks animal were sacrificed, tissues collected, snap frozen in liquid nitrogen and stored at −80°C until analysis. Whole blood was used to measure liver function and glucose concentrations, while plasma was used for lipid analyses. Total lipids were extracted from adipose, liver and skeletal muscle and analyzed for fatty acid profile, as well as cholesterol and triglyceride accumulation. Gene expression was measured via qPCR in each tissue for GAPDH, FATP 1–6, FAS, FABP4, PPAR α/β/γ, SREBP1 & 2, NPC1L1 and SRBI. qPCR results confirmed via western blot. [Supported by NIH GM56850]
HIGH‐FAT DIET: EFFECTS ON SERUM LIPID PROFILE IN AN EXPERIMENTAL MODEL
Authors: Perris Paula Daniela , Feliu María Susana , Fernandez Inés , Slobodianik Nora
Published: June 2021

Previous studies demonstrated statistically significant increase (p<0.01) in the concentration of triglycerides(TG) in a group fed with a diet rich in saturated fatty acids and another group fed with a diet high in monounsaturated fatty acids. The objective of this study is to analyze the same parameters in rats fed with the same diets for a longer period. Wistar rats (n=12) at weaning were divided into 2 groups(S,M) and fed during 40 days diets with 20% protein and 50% fat and complete in other nutrients. The source of fat was: butter and cocoa butter(S), olive and soybean oils(M). The control group(C) received isocaloric diet containing casein.

Rats were killed and serum Triglyceride concentration, total cholesterol (TC) and HDL cholesterol were determined by enzymatic‐colorimetric method; LDL was calculated (Friedwald equation).

The results (mg/dL) expressed as mean+SD were: TG:S=191.1+49.2;M=152.5+87.3;C=98.3±26.9;TC:S=95.0±6.7;M =95.4±10.7;C=83.3±7.2;HDL:S=41.1±5.6;M=48.9±6.4;C=42.2±15.5;LDL:S=15.7±6.2;M=15.9±9.0;C=21.4±11.7.

The study demonstrated that the administration of diets high content in fat for long period of time increases only the TG in group S (p< 0.01) compared with C. The global analyses suggest that the administration of a diet high in saturated fat, produces the same effect on serum lipid profile independently of the period of time.

Supported by UBA(B074)
Nutrition intervention for adults with intellectual or developmental disabilities residing in group homes: MENU‐AIDDs
Authors: Humphries Kathleen , Traci Meg Ann , Seekins Tom W.
Published: June 2021

Researchers with the CDC‐sponsored Montana Disability and Health Program developed the health promotion program Materials supporting Education and Nutrition for Adults with Intellectual or Developmental Disabilities (MENU‐AIDDs). The nutrition intervention was created via PAR research techniques to improve the nutrition and food systems in community‐based group homes for adults with IDD. To date, MENU‐AIDDs training and materials have been disseminated 90 group homes in Montana. This presentation will describe the MENU‐AIDDs nutrition intervention for adults with IDD and report on the results of the Montana dissemination and training of MENU‐AIDDs. Outcomes included measures of dietary intake (through menu review and food frequency questionnaire), residents’ body weights, and their gastrointestinal health improvements. Process evaluation results will also be shown, including group homes’ fidelity to the program and its acceptance by consumers, direct care staff, and home administrators. The value of MENU‐AIDDs is demonstrated as an acceptable, accessible, effective health promotion program to improve nutrition and nutrition‐related secondary conditions in community‐dwelling adults with IDD. Project funded through a cooperative agreement with the Centers for Disease Control and the Montana Department of Public Health and Human Services.
A Survey of Micronutrient Supplementation for Patients with HIV
Authors: Greene Michael Todd , Tam Chick F
Published: June 2021

Based on prior research, daily Selenium supplementation can suppress the progression of HIV‐1 viral burden and provide indirect improvement of CD4 count. Research supports the use of Selenium as a simple, inexpensive, and safe adjunct therapy for HIV. The testing hypothesis was, “Would patients with HIV take micronutrient supplements if they would improve their health?” Two study populations were surveyed. The first (n=103) was of university nutrition students who were chosen for their nutritional knowledge and to serve as a reference group. The second (n=88) was of people with HIV. This group may or may not have knowledge and understanding about micronutrients or supplements. All subjects were asked, “Do you think you would take a supplement if you knew it would improve your health?” Results showed that the HIV population had a significant favorable answer to the question when compared to those of the student population. There is a positive attitude to consume micronutrients for people with HIV if by including micronutrient supplementation in their diet would improve their health. For the patient with HIV who wants to have improved health status, micronutrient supplementation may be an answer. All beneficial nutrients should be derived from food, however, it is suggested that people with HIV who take micronutrient supplements will have improved health and quality of life. There was no research support for this study.
Acidic diet and bone mineral content in older men: the CHAMP‐study
Authors: Heer Martina , Chen Charles , Cumming Robert G , Lichfield Melisa , Naganathan Vasikaran , Blyth Fiona , Creasey Helen , Waite Louise , Handelsman David J , Le Couteur David , Sambrook Philip , Seibel Markus J
Published: June 2021

Dietary habits may contribute to bone loss in older adults. We studied the effect of dietary potential renal acid load (PRAL) on bone health in a representative sub‐set of older men (n= 920, age 76.5 ± 4.9 (SD) yrs; body weight 80.1 ± 12.8 (SD) kg) of the CHAMP (Cumming et al. 2009) population‐based cohort. Average daily PRAL was calculated from a self‐reported dietary habit questionnaire. Total bone mineral content (BMC) and density (BMD) were analyzed by DXA (Hologic). Fasting morning serum samples were analyzed for intact parathyroid hormone (PTH), procollagen type I aminoterminal propeptide (a bone formation marker) as well as urinary cross‐linked aminoterminal telopeptide (a bone resorption marker). Men with an acidic diet (508, 55%) had significantly lower BMC (adjusted mean: 2488 vs. 2577g; P<0.001) and BMD (adjusted mean: 1.13 vs. 1.16 g/cm2; P=0.01) compared with men having an alkaline diet (412, 45%) after adjustment for confounders (age, body size, smoking, medication affecting bone mass or muscle strength). Additional adjustment for PTH and renal function did not change the results. Bone formation and resorption markers were unrelated to PRAL. We conclude that a predominantly acidic diet is associated with lower bone mineralization, which may increase the risk of osteopaenia and osteoporosis in older men.
CordyMax extends the lifespan in an aging model: A preliminary report
Authors: Tan Ningzhi , Zhang Yan , Yang Jieying , Zhao Chunsheng , Zhu Jia‐Shi
Published: June 2021

Cordyceps sinensis (Cs) is traditionally believed as an anti‐aging TCM herb. We have reported the anti‐fatigue and endurance enhancement properties of CordyMax (CM), a mycelia fermentation product of Cs, and its benefits in glucose‐lipid‐energy metabolisms. In this study we examined its anti‐aging effects in mice. A total of 192 ICR mice (12 months of age, half males and half females) were randomized into 4 groups, receiving either vehicle or CM at a dose of 0.5, 1.0 or 1.5 g/kg mixed with forage. Calorie intake was monitored twice per week and adjusted carefully to match the calorie intake of controls. Continuous oral CM (72 wks so far) showed: (1) no significant differences in body weight and calorie intake among the groups; (2) compared to controls, the 75% survival time extends 98, 94 and 108 days in the CM groups (0.5, 1.0 and 1.5g/kg, respectively), and the 50% survival time extends 66, 10 and 39 days, respectively. Kaplan‐Meier Survivor analysis showed significantly extended lifespan and reduced risks of death by CM: p=0.049 (Wk36), p=0.036 (Wk40), p=0.059 (Wk48), p=0.004 (Wk60), p=0.027 (Wk 64), p=0.041 (Wk 68) with the best survivor curve for the low dose CM treatment (equivalent to the human dose). This study demonstrates that CM extends the lifespan in mice, while the experiment continues. All the health benefits of CM (anti‐oxidation, the effect in metabolisms and aerobic exercise capacity) support the anti‐aging function of CM.
Female rats fed low level whole cottonseed for life develop apparent brain neurofibrillary tangles
Authors: Semon Bruce Andrew
Published: June 2021

13 female rats were fed for their lifetimes a 14% soy protein diet as control. 13 rats were fed control diet plus 0.013% whole cottonseed (WCS 0.013%) and 13 rats were fed control diet plus 0.13 % whole cottonseed (WCS 0.13%). Apparent brain neurofibrillary tangles were found in one of three of the longest surviving WCS 0.013% rats and in five of five of the longest surviving WCS 0.013% rats. No neurofibrillary tangles were found in brain of control rats. Lifetime feeding of small amounts of WCS leads to brain findings seen in human Alzheimer's. This study was funded privately by the Wis. Institute of Nutrition,
Increased microparticle procoagulant activity in mice lacking alpha(1,3)‐fucosyltransferase‐IV and –VII
Authors: Wang Huili , Morales‐Levy Maria , Homeister Jonathon W.
Published: June 2021

Fucosylation of selectin ligand glycans by alpha(1,3)‐fucosyltransferases (FucT)‐IV or ‐VII is required for sialyl Lewis x formation and selectin‐binding activity. FucT‐IV(−/−)/FucT‐VII(−/−) mice (DKO) have a 43% decrease in the time to arterial thrombosis due in part to enhanced whole blood platelet aggregation. We evaluated the contribution of the coagulation system to enhanced thrombosis. Fibrinometric determinations of intrinsic and extrinsic pathway activity were not different between WT (n=8) and DKO (n=8) mice [prothrombin time: WT = 12.4±0.3 vs DKO = 12.1±0.4, p=0.11; activated partial thromboplastin time: WT = 29.5±1.9 vs DKO = 28.2±2.6, p=0.28]. Similarly, parameters of the calibrated automated thrombography assay were not different between WT (n=10) and DKO (n=10) mice [lag time: WT = 4.1±1.4 vs DKO = 4.2±0.8, p=0.82; time to peak: WT = 10.4±2.1 vs DKO = 9.4±1.8, p=0.28; peak height: WT = 21.2±6.0 vs DKO = 23.7±4.3, p=0.29; endogenous thrombin potential: WT = 359±123 vs DKO = 336±77, p=0.6]. In contrast, total microparticle procoagulant activity was elevated 3 fold in DKO (n=8) mice compared to WT (n=8) mice [WT = 0.21±0.2 vs DKO = 0.6±0.2, p=0.02], due primarily to microparticle tissue factor‐dependent activity [WT = 0.08±0.1 vs. DKO = 0.23±0.22, p=0.1]. Microparticle tissue factor activity contributes in part to the enhanced thrombosis in DKO mice. Support by AHA FTF Award 0275023N and RO1‐HL090823.
Comparative Studies on Six Unfractionated Heparin Batches from China
Authors: Sadeghi Nasir , Hoppensteadt Debra , Iqbal Omer , Jeske Walter , Walenga Jeanine M. , Fareed Jawed
Published: June 2021

Most heparin originates in China. Although the FDA has implemented stringent analytical and biological stipulations, there are still differences in the biologic actions of these drugs. The purpose of this study was to compare six batches of UFH from a single Chinese supplier to demonstrate any potential differences among these agents. All heparins were profiled for molecular weight using a HPLC. Anticoagulant activity was measured using whole blood activated clotting time (ACT) and plasma based assays (PT, aPTT, Heptest, TT, anti‐Xa and IIa activities). All heparin preparations had a comparable molecular weight (15.8 to 17.3 kDa). In the PT and TT assays no differences were noted in the six agents, however in the Heptest assay, one heparin showed markedly weaker activity than the other products. In the aPTT assay marked differences among agents were observed. Amidolytic anti‐IIa activities and anti‐Xa activity were comparable; IC50 values ranged from 1.4 to 1.9 μg/ml and 1.6 to 2.2 μg/ml for the anti‐IIa and anti‐Xa, respectively. These results showed that while all of the heparins had comparable molecular profiles; the anticoagulant activity of these preparations varied in some assays. While the differences were minimal in the anti‐Xa and anti‐IIa assays, marked differences were noted in the aPTT and ACT. Thus, there is a need for additional testing to compare heparin preparation to assure minimal batch variations.
Bowel Morphologic evaluation in Experimental Administration of Wine and a Pesticide
Authors: Cavalcanti Karen Pena , Gurgel Ana Pavla , Mendes Tiago , Barreto Pedro , Souza Ivone A , Filho Nicodemos Teles , Cabrita Antonio Silverio
Published: June 2021

The red wine is described as cadioprotective and chemoprotective. However, there are still many unclear aspects related with this beverage, which should be considered when thinking about the risk/benefit relationship in red wine consumption. The aim of this study was to evaluate the incidence of the aberrant crypts (AC) and neoplasm lesion in the experimental administration of red wine in the presence of the pesticide 1‐naphtyl N‐methyl carbamate (1NC). Twenty Wistar males rats 8 weeks of age were distributed randomly in 2 groups with 10 animals each. Group I constituted a control group with no manipulation. The group II was submitted to the administration of the 3.52 ml/Kg of red wine, by gavage, during 8 weeks. Also, the group II was submitted to the administration of 1NC in the drinking water in the concentration of 60mg/l during 8 weeks. All the animals were sacrificed and by the end of twenty‐eight weeks. The bowel of control had no lesions. The incidence of AC observed in the group II was 2.6 Â± 5.68 (6%) in the rectum, 8.1 Â± 9.97 (60%) in the colon and 13.8 Â± 3.26 (34%) in the cecum. The bowel of control group had no lesions. Therefore, there were no neoplasm lesions
Expression of Ang 1–7 receptor (MAS receptor) in aortic tissue during pregnancy‐induced hypertension in rats
Authors: Anguiano‐Robledo Liliana , Avila Massiel Alfonsina , Vazquez‐Cruz Beatriz , Lopez‐Sanchez Pedro
Published: June 2021

Low vasopressor response to angiotensin II is characteristic during normal pregnancy. In preeclampsia (PE), this effect is lost. A novel renin‐angiotensin system component, the Ang 1–7 receptor (MAS receptor) shows vasodilatory, anti‐hypertrophic and pro‐apoptotic actions. It is not well known the role of this receptor during PE. The aim of this work was to study MAS receptor expression in aortic tissue during PE. We used a subrenal aorctic coarctation (SRAC) model in female Wistar rats, measuring blood pressure, proteinuria and pups weight. Aortic tissue samples were homogenized and immunoblotted using an Anti‐MAS antibody. We found hypertension, proteinuria and low‐weight pups in SRAC‐pregnant rats. We also found MAS receptor expression in both, pregnant non‐SRAC and pregnant SRAC groups. In pregnant non‐SRAC rats, MAS was expressed markedly. In pregnant SRAC rats however, we found a lower expression of this receptor. These results suggest that MAS expression is increased in normal pregnancy and decreased expression of this receptor during preeclampsia may indicate a role in the pathophysiology of this complication. Supported by SIP‐IPN 20090153 and 20090396 grants.
Angiotensin (1–7) Induced Inhibition of the Nerve‐Stimulation Induced Release of Norepinephrine (NE) and Neuropeptide Y (NPY) from the Rat Mesenteric Arterial Bed: Role of Prostacyclin
Authors: Murray Jessica M. , Macarthur Heather , Westfall Thomas C.
Published: June 2021

We have observed that Ang‐(1‐7) produces a significant decrease in the nerve stimulation (NS)‐induced release of both NE and NPY as well as perfusion pressure of the perfused mesenteric arterial bed of the rat. In the present study we examined the hypothesis that the Ang‐(1‐7) induced inhibition of sympathetic neurotransmission is mediated at least in part by prostacyclin (PGI2), which is well known to inhibit sympathetic neurotransmission and to mediate part of the vasodilator action of Ang‐(1‐7). Experiments were carried out using the mesenteric arterial bed obtained from 10–12 week old Sprague Dawley and Spontaneously Hypertensive Rats (SHR). The effect of Ang‐(1‐7) on the NS‐evoked release of NE and NPY was determined before and after the administration of indomethacin to block PGI2 synthesis and before and after the administration of the PGI2 receptor blocker CAY 10441. Results obtained to date support our hypothesis that PGI2 mediates the actions of Ang‐(1‐7). (Supported by HL60260 and NIGMS008306)
High intravascular pressure decreases endothelial Ca2+ pulsars and impairs endothelium‐dependent vasodilation in mouse mesenteric arteries
Authors: Sonkusare Swapnil K. , Heppner Thomas J. , Bonev Adrian D. , Hannah Rachael M. , Talline Yvonne , Kotlikoff Michael I. , Nelson Mark T.
Published: June 2021

Ca2+ pulsars are inositol 1,4,5‐triphosphate (IP3) receptor‐mediated Ca2+ events in endothelial cells. Increase in Ca2+ pulsars by acetylcholine (ACh) is associated with endothelium‐dependent vasodilation. The objective of this study was to evaluate the effect of intravascular pressure on Ca2+ pulsars and endothelium dependent vasodilation of resistance arteries. Third‐order mesenteric arteries (MAs) from C57BL6 mice were pressurized at 80 or 120 mmHg and were allowed to develop myogenic tone (26± 1% and 36 ± 1 % at 80 and 120 mmHg respectively, n=9). Endothelium dependent vasodilation to ACh (5 μM) was significantly higher at 80 mmHg compared to 120 mmHg (76.8 ± 7.8 % and 30.1 ± 4.6% respectively, n=4–6, p<0.05). To evaluate the effect of intravascular pressure on Ca2+ pulsars, we used MAs from mice that express a calcium biosensor (GCaMP2) exclusively in endothelial cells. Frequency of Ca2+ pulsars (pulsars/second/site) was higher at 80 mmHg compared to 120 mmHg (0.11 ± 0.01 and 0.07 ± 0.01 respectively, n=15–31 sites). Following ACh treatment, the Ca2+ pulsar frequency increased to 0.19 ± 0.02 at 80 mmHg compared to 0.09 ± 0.01 at 120 mmHg (n=9–10 sites, p<0.05). Taken together, these results indicate that impaired endothelium‐dependent dilation of resistance arteries at high intravascular pressure is associated with a decrease in Ca2+ pulsars in the endothelial cells. Supported by NIH HL44455.
Coronary Endothelium: New Pharmacological Target for Heart Hypertrophy/Failure
Authors: Sun Xiaowei , Ku David D.
Published: June 2021

Extensive studies have shown that chronic heart hypertrophy/failure often accompanied by abnormalities in coronary endothelial (CEC) function. In a selective right ventricular hypertrophy (RVH) rat model we noted for the first time that the right CEC function was significantly increased prior to the development of RVH, while the left coronaries in the unaffected left ventricle was not altered. As cardiac hypertrophy developed, marked depression of CEC function was noted. To further investigate the significance of CEC function during the development of RVH, we studied the effects of both early (prevention) and late (rescue) treatments with a natural product (garlic) or a standard statin (rosuvastatin, RS). Oral treatment with 1% garlic supplemented diet either 1 day before or 1 day after the induction of RVH showed significant preservation of CEC function and prevention of RVH. Similar treatments with garlics without its active ingredient, allicin, failed to produce a protective effect. Oral treatment with a water‐soluble HMG‐CoA reductase inhibitor, RS, 1 week before as well as 1 week after the induction of RVH also effectively prevented CEC dysfunction and RVH. Conversely, inhibition of CEC function with L‐NAME treatment exacerbated the development of RVH. Taken together, results of our studies demonstrate that modulation of CEC function provides a novel approach for the management of cardiac hypertrophy.
Metoprolol reduces central sympathetic drive and restores cardiac output during the development of ischemic heart failure in conscious rats
Authors: Burris Sarah K , Knuepfer Mark
Published: June 2021

Increased sympathetic nerve activity (SNA) likely contributes to pathological changes observed in heart failure. Beta‐adrenergic receptor (B‐AR) blockers are beneficial in treating heart failure by reducing remodeling and mortality. We hypothesized that systemically administered metoprolol, a B‐AR antagonist, will act centrally to reduce SNA following myocardial infarction (MI) during the development of ischemic heart failure. Sprague‐Dawley rats were instrumented to record arterial pressure, heart rate, cardiac output, and adrenal and renal SNA. After recovery, parameters were recorded prior to and for two weeks following MI. Cardiac function was assessed before and weekly post‐MI by echocardiography. Infarct size was confirmed histologically. SNA levels were estimated by ganglionic blockade. Metoprolol treatment (25 mg/kg/day, sc, Alzet mini‐pump) began four days post‐MI. MI reduced arterial pressure and cardiac output, whereas heart rate and renal and adrenal SNA increased. Metoprolol further decreased arterial pressure and heart rate but restored cardiac output and reduced SNA back to pre‐MI values. We demonstrated that SNA increases after MI and that peripheral administration of metoprolol reverses this increase. Our data suggest that metoprolol acts, at least in part, on central B‐AR to reverse elevated SNA. Support: USPHS DA0017371, HL091440 & T32 GM008306.