bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline serum n‐3 eicosapentaenoic acid concentration is associated with subsequent mood disturbance during the acute stress of military survival school training
Authors: Farina Emily Kristin , Grohmann Kyle , Biedenkapp Joseph C. , McClung James P. , Lieberman Harris R.
Published: June 2021

Observational data suggest positive relationships between n‐3 fatty acids (FA) and mental health. FA metabolism may be disrupted in depression, but relationships between n‐3 FAs and acute stress have not been examined. Thus, we utilized multiple regression modeling to determine associations between fasted baseline serum n‐3 FA expressed as % of total FA [α‐linolenic acid (ALA, 18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6)]; midday baseline saliva hormone concentrations; and mood among US Army Soldiers (n=59, 26.9±2.9 y) during Survive, Evade, Resist, Escape (SERE) school. Mood, assessed by the Profile of Mood States, was evaluated following an acutely stressful simulated interrogation conducted during ~12 days of intermittent sleep and food deprivation. ALA was associated with increased cortisol (p<0.01), and EPA was inversely associated with testosterone (p=0.04) and dehydroepiandrosterone‐sulfate (p=0.02), after adjustment for covariates. EPA was associated with increased total mood disturbance (p=0.01), tension (p=0.02), depression (p=0.03), anger (p=0.05), fatigue (p=0.02), and confusion (p=0.01), after adjustment for hormones and covariates. These data suggest higher EPA levels prior to stress exposure may be negatively associated with acute stress resilience.

Grant Funding Source: Office of Naval Research/US Army Medical and Research Materiel Command
Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition
Authors: Ronis Martin , Baumgardner January , Marecki John , Henning Leah , Wu Xianli , Shankar Kartik , Cleves Mario , Gomez‐Acevedo Horacio , Badger Thomas
Published: June 2021

To determine if dietary fat type influences nonalcoholic fatty liver disease (NAFLD), male SD rats were overfed low (5%) or high (70%) fat diets containing olive oil (OO), corn oil (CO) or echium oil (EO) using total enteral nutrition (TEN) for 21 d. Overfeeding 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P< 0.05). Significant differences in hepatic gene expression signatures were associated with greater fatty acid synthesis, ChREBP and SREBP‐1c signaling, and increased fatty acid transport (P<0.05) in the 5% OO compared to 5% CO group. The OO groups had macrosteatosis, but no evidence of oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro‐ and macrosteatosis or only microsteatosis, respectively; increased oxidative stress; and increased necrotic injury relative to their respective 5% groups (P<0.05). Oxidative stress and necrosis correlated with peroxidizability of hepatic triglycerides. Increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis were observed in the 70% OO relative to the 70% CO group. When 70% OO diet was overfed for 50 d there was no progression of injury beyond simple steatosis. Therefore, dietary fat type influences the progression of NAFLD and a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis. Supported in part by USDA, ARS‐CRIS 6251–51000‐005–004S.
Impact of parenteral lipid emulsions on the metabolomic phenotype in preterm TPN‐fed piglets
Authors: Kulkarni Madhulika A , Vlaardingerbroek Hester , Stoll Barbara , Ilkayeva Olga , Newgard Christopher , Olutoye Oluyinka , Van Goudoever Johannes B , Burrin Douglas
Published: June 2021

Lipids in parenteral nutrition provide essential fatty acids and are a major source of energy for hospitalized neonates. Intralipid (IL) is the only approved lipid emulsion in the U.S, but new generation emulsions include Omegaven (OV) and SMOFlipid (SL). There are no studies describing the metabolite profile in neonates comparing different type of lipid emulsions. Our aim was to perform metabolomic profiling of liver and muscle tissue in TPN‐fed piglets given different lipid emulsions. Preterm pigs were assigned to 4 groups (7–14 pigs/group; equal daily macronutrient intake with 5 g/kg lipid): PN+IL, PN+OV, PN+SL and an enteral group fed milk formula (EN). Plasma, muscle and liver tissue were collected after 14 d and subjected to analysis of fatty acid, amino acid and citric acid cycle metabolites by various HPLC and GC/MS methods. In liver tissue, acyl‐CoA species were most abundant for the dominant fatty acids in the respective lipid emulsions. Tissue free carnitine in EN pigs was 4‐fold higher than TPN groups and this resulted in a reduced liver, but not muscle acyl‐carnitine levels. The acyl‐CoA:acyl‐carnitine ratios were higher in liver than muscle tissue and also higher in all TPN groups vs EN. Among citric acid cycle intermediates, only citrate was higher in EN vs. all TPN groups. We conclude that metabolomic profiles revealed a carnitine deficiency in TPN groups that suggests impaired hepatic fatty acid oxidation.

Grant Funding Source:USDA
A standardized method for preparation of potatoes and analysis of their resistant starch content: Variation by cooking method and service temperature
Authors: Jackson Matthew Irick , Idso Laura A , Combs Gerald F , Beals Katherine , Raatz Susan K
Published: June 2021

Consumption of resistant starch (RS) may lead to reduced glycemia, improved satiety, and beneficial changes in gut microbiota due to its unique digestive and absorptive properties. We developed a standardized protocol for preparation of potatoes in order to assess their RS content and modified a commercially available assay for RS to incorporate microscale, high‐throughput processing, quantitative standard curves for amylose and amylopectin and inclusion of a bacteriostatic agent to prevent alteration of carbohydrate profile by microbial contamination. We examined 3 North Dakota potato (Yukon Gold, Red Norland and Russet Burbank) varieties subjected to two methods of preparation (baking at 167° C for 65–80 minutes or boiling at 100° C for 10–11 minutes until tender) and at three service temperatures (hot, 60° C; chilled 4° C for 6 days and chilled followed by reheating to 60° C). RS was analyzed by 3‐way ANOVA. Results show that the RS (g/100g) composition varied by method of preparation (p < 0.0001) and service temperature (p < 0.0001) but not variety (p >; 0.05). Baked preparations of potatoes had higher RS content than boiled preparations, and hot potatoes had less RS than either chilled or reheated potatoes. Knowledge regarding the effects of preparation methods on the RS content of potato products may assist in dietary decision making. Work was supported by USDA 5450–51000‐049–00D and the U.S. Potato Board.
Chronic distal digesting of starch reduces subsequent starch digestion through a post‐translational mechanism which reduces mucosal disaccharidase activities
Authors: Yan Like , Avery Stephen E , Vohra Firoz A , CHACKO SHAJI K , Nichols Buford L , Hamaker Bruce R
Published: June 2021

Feeding of slowly digested starch is hypothesized to suppress glycemic responses to ingested starch.

Aim

Determine if location of starch digestion can regulate subsequent starch digestion rates.

Methods

Rice starch was encapsulated in alginate microspheres to target distal sites of digestion (Mol. Nutr. Food Res. 2009, 53, S121–S130). Groups of eight 8‐wk old mice were fed rice maltodextrin (proximal), 0.5% microspheres (middle), or 1% microspheres (distal) targeted diets for 7 d. The mice were fed low 13C‐rice diets from conception. At 10 wks age they were trained to eat from 12–12.5 after the last previous feed (hLF). 13C‐enriched maize starch (MPE: 0.1 ± 0.003) was then fed. Blood glucose was measured by glucometer and spotted on filter paper for 13C‐glucose analysis at 12, 12.5 and 14 hLF. Blood glucose was derivatized as penta‐acetate and run by GC‐C‐IRMS for 13C‐enrichment (MPE%). Activities of mucosal sucrase (S) and glucoamylase (G) were measured by Dahlqvist assays. Gene expressions were assayed by AB fluidic arrays.

Results

Prandial MPE% responses and mucosal S and G were reduced by the encapsulated starch diets (ANOVA: 0.001). The jejunal message levels for S were not changed.

Conclusion

7d of distal starch digestion regulated starch digestion by adaptation of S activities. The S messages remained constant suggesting a post‐translational control of sucrase activity by chronic distal starch digestion.

Grant Funding Source: Whistler Center and CNRC/ARS/USDA
Reduced glycemic response to starch feeding of Mgam null mice is buffered by increased endogenous gluconeogenesis
Authors: Lin Amy Hui‐Mei , Diaz‐Sotomayor Maricela , Quezada‐Calvillo Roberto , Avery Steven E , Chacko Shaji K , Yan Li‐ke , Ao Zi‐hua , Hamaker Bruce R , Nichols Buford L
Published: June 2021

Six digestive enzymes are required to break down starch polymers to free glucose before intestinal absorption. Understanding of the contribution of individual digestive enzymes on this process may provide a new strategy to manage prandial glucose.

Objective

Determine the effect of poor starch digestion causing by the absence of maltase‐glucoamylase (Mgam) on glycemia response.

Method

Mgam null mice and wild type (WT), 4 each, were fasted for 12 h and then fed normal corn starch. They were sacrificed at 16 h. Timed blood glucose and total free glucose, soluble oligomers, and starch residues remaining in the small intestine (SI) were measured.

Result

Glycemic response to feeding in the 2 genotypes of mice was not different. However, after 4 h the persistence of indigested carbohydrates in SI of null mice (60%) was higher than WT (30%). Null and WT mice had similar amylolysis activity (oligomers/residual starch), but null mice had lower glucosidase activity, (free glucose/ residual starch: 0.4 null and 0.9 WT mice).

Conclusion

It is known that Mgam null mice have lower glucosidase activity in vivo, and in vitro. Here we report that WT was associated with more complete lumenal digestion of granular starch, but the blood glucose response of null mice was fully compensated by gluconeogenesis. Reduced starch glucogenesis in null mice is buffered by endogenous glucose production which obscures the prandial glycemia response.

Grant Funding Source: USDA ARS 6250–51000‐052 and the internal funding from Whistler Center for Carbohydrate Research at Purdue Univ.
Dietary protein intake, energy deficit, and nitrogen balance in normal‐weight adults: a randomized controlled trial
Authors: Margolis Lee M , Cao Jay J , Whigham Leah D , McClung James P , Combs Gerald F , Young Andrew J , Pasiakos Stefan M
Published: June 2021

Consuming protein at levels higher than the recommended dietary allowance (RDA) may be metabolically advantageous for overweight and obese individuals attempting weight loss. However, the dose‐response characteristics that define the optimal level of dietary protein necessary to sustain measures of metabolic homeostasis during short‐term energy deficit (ED) in normal‐weight adults remain unclear. Thirty‐two men and 7 women participated in a 31‐day randomized trial providing diets containing protein at either the RDA (0.8 g·kg−1·d−1), 2X‐RDA (1.6 g·kg−1·d−1), or 3X‐RDA (2.4 g·kg−1·d−1). A weight maintenance (WM, days 1–10) period was followed by 21 days of ED (days 11–31); energy intake was restricted to 60% of daily requirements. Nitrogen balance (NBAL) was assessed during WM (day 9) and throughout ED on days 14, 17, 24, and 30. Independent of protein, NBAL (mgN·kg−1·d−1) was lower (P < 0.05) at the start of ED (day 14, −40 ± 5) compared to WM (day 9, −10 ± 5). NBAL remained negative at the conclusion of ED (day 30) for RDA (−39 ± 8). However, NBAL increased (P < 0.05) rapidly and was maintained at levels comparable to WM beginning on day 17 for 2X‐RDA (0 ± 8), yet failed to achieve WM levels until day 30 (−7 ± 10) for 3X‐RDA. These data confirm that high protein diets conserve NBAL during short‐term ED, but suggest no beneficial effect of protein at levels beyond 2X‐RDA, as 3X‐RDA failed to further enhance nitrogen adaptation.

Supported by USAMRMC and USDA ARS
Folate in human skin: its correlation with serum levels, and the unusual abundance in the epidermis of 5‐methyltetrahydrofolate
Authors: Hasoun Luai Z. , Bailey Steven W. , Outlaw Kitti K. , Ayling June E.
Published: June 2021

Understanding the biology of folates in human skin is of considerable interest not only because they may be at risk for degradation by ultraviolet light, but they may also have photoprotective properties. We have previously measured 5‐methyltetrahydrofolate (5‐MTHF) in fresh ex vivo skin samples by a recovery validated extraction method, and found that epidermis contains an order of magnitude higher concentration than the dermis. Skin samples from black and white subjects not exposed to light were not different from each other (FASEB J. 2011, 25:608.2). We now show that the abundance of 5‐MTHF in both layers of skin in relation to total folate (TFOL) as determined by microbiological assay are highly and linearly correlated with the serum folate status. Surprisingly, while the percentage of TFOL present as 5‐MTHF in the dermis was typical of other organs, it constituted an unusually high percentage in the epidermis, increasing (to over 70%) as serum folate (and thus skin total folate) decreased. The high percentage of 5‐MTHF in the epidermis, and its maintenance in mildly folate deficient subjects, points to a special role for this form of folate in skin, perhaps as a scavenger of singlet oxygen produced in UV induced photosensitization reactions (FASEB J. 2007, 21:2101–7).

Supported by NSF 009185353; LZH is recipient of a predoctoral fellowship from the Graduate Research Scholars Program of Alabama.
Anthranilic acid and 3‐hydroxyanthranilic acid, but not kynurenic acid, are associated with plasma pyridoxal‐5 phosphate levels
Authors: Reginaldo Christina Dichoso , Selhub Jacob , Paul Ligi , Jacques Paul , Wang Thomas , Gerszten Robert
Published: June 2021

Both high inflammation and low pyridoxal 5′‐phosphate (PLP) status are associated with chronic diseases such as cardiovascular disease and diabetes. A hallmark of inflammation is the induction of indoleamine‐2,3‐dioxygenase (IDO) by the inflammatory cytokine interferon‐γ, leading to the degradation of tryptophan through the kynurenine pathway. Since PLP is a cofactor for many of the enzymes in the kynurenine pathway, we hypothesize that plasma PLP levels could modulate the formation of some of the kynurenines that require PLP as a cofactor for synthesis. To test this, a secondary data analysis was performed on metabolomics data from 1,868 subjects from Framingham Offspring cohort, Exam 5. Using generalized linear models, anthranilic acid (AA) and 3‐hydroxyanthranilic acid (OH‐AA) were found to be positively associated with PLP after adjusting for age, sex, BMI, creatinine, smoking status, and NSAID use (p=0.04 and 0.02, respectively). A 10 nmol/L increase in PLP status was associated with 0.5% and 1.1% increases in AA and OH‐AA, respectively. Kynurenic acid (KA) was not found to be associated with PLP (p = 0.41). Results suggest that AA and OHAA are weakly associated with plasma PLP. Supported by USDA cooperative agreement 51520–008‐045 and NHLBI Framingham Heart Study (Contract No.N01‐HC‐25195).

Grant Funding Source: USDA cooperative agreement 51520–008‐045 and NHLBI Framingham Heart Study (Contract No.N01‐HC‐25195).
Folic acid supplementation for 12 weeks modifies gene expression in leukocytes in men with low folate status
Authors: Paul Ligi , Razzari Cristina , Sampietro Francesca , Fontana Gessica , Fermo Isabella , Reginaldo Christina , Cattaneo Marco , D'Angelo Armando , Jacques Paul F , Selhub Jacob
Published: June 2021

Folate nutritional status and the 677C>;T polymorphism of methylene tetrahydrofolate reductase (MTHFR) are known to influence gene expression. The objective of this study was to determine if supplementation with 400μg of folic acid for a period of 12 weeks will change gene expression in individuals with low folate status. We also determined the influence of MTHFR 677C>;T on these outcomes. 20 men homozygous for the variant allele of MTHFR and 20 men without the polymorphism, aged 45–65, whose average plasma folate was 10.53 nmol/L were selected for the study from Milan, Italy. The subjects were randomized to receive placebo or 400μg folic acid tablets. Blood samples were collected before and after 12 weeks of supplementation. When compared to subjects on placebo, those who received folic acid had higher folate concentration (9.78 nmol/L vs 44.56 nmol/L, P<0.0001) and lower homocysteine concentration (12.59 μmol/L vs 9.05 μmol/L, P=0.1) in plasma at the end of 12 weeks. Changes in gene expression in leukocytes were determined by microarray analysis. Expression of multiple genes for pro‐inflammatory chemokines and interleukins decreased with folic acid supplementation, especially in TT genotypes of MTHFR. Folic acid supplementation at current RDA can potentially alter inflammation in individuals with low folate status. Supported by USDA grant 2005–35200‐15296 & USDA cooperative agreement 51520–008‐04S.
Choline Modulates Soluble‐Endoglin (sEng) and Vascular Endothelial Growth Factor (VEGF) in Cultured Human Placental Trophoblasts
Authors: Andrew Benjamin Yates , Jiang Xinyin , Jones Sara , Caudill Marie A , Brannon Patsy M
Published: June 2021

Altering the balance between the anti‐angiogenic factors, soluble fms‐related tyrosine kinase‐1 (sFLT1) and sEng, and the angiogenic factors, VEGF and transforming growth factor beta (TGF‐β), contributes to preeclampsia (PE) and persistence of hypoxia (Hx). Increasing sFLT1 and sEng may sequester VEGF and TGF‐β. Recently we showed that supplemental choline reduced placental sFLT1 mRNA and maternal plasma sFLT1 in pregnant women and cultured trophoblasts (HTR‐8/SVneo). To determine if choline regulates sEng production and VEGF gene expression independently or interactively with Hx, HTR‐8/SVneo cells were cultured in a 2×4 factorial design in either normoxia (20% O2, Nx) or Hx (1% O2) and 13 μM, 18 μM, 28 μM (control) or 48 μM for 96 hours. Results were analyzed by 2‐way ANOVA (SigmaPlot). Low choline (13 μM) under Nx, but not Hx, increased media sEng (14%, p=0.036) and mRNA levels of VEGF (160.9%, p<0.001), HIF‐1α (36.2%, p<0.001) and HIF‐2α (63.3%, p<0.001) compared to control. Hx also increased media sEng (9.25%, p<0.001) and VEGF mRNA levels (114.18%, p<0.001) across all choline levels. Thus, low choline modulates, under Nx but not Hx, the anti‐angiogenic sEng as well as the angiogenic VEGF, thereby mimicking the effects of Hx. Low choline under Nx, therefore, may alter the resulting balance of antiangiogenic and angiogenic factors contributing to PE. Funded by USDA NIFA AFRI003397
Baked purple potato extracts, containing anthocyanins, elevate apoptosis in colon cancer stem cells via p53 independent pathways
Authors: Vanamala Jairam , Charepalli Venkata , Reddivari Lavanya
Published: June 2021

We have previously shown that baked purple potato anthocyanins (PA) suppress proliferation and elevate apoptosis in human colon cancer cell lines HCT‐116 (p53 +/+ and K‐ras−/−) and HT‐29 (K‐ras+/+). However, the effect of PA on human colon cancer stem cells (CSCs) is not yet known. The objectives of this study were 1) to evaluate the metabolite profiles of fresh vs. baked potato; and 2) to evaluate the anti‐proliferative (BrdU and Cell counting) and proapoptotic (TUNEL) properties of PA against CSCs (positive for CD44, CD133, Aldehyde Dehydrogenase markers) with functioning p53 and attenuated p53 (shRNA). Principal component analysis of 1600 metabolite fragments from fresh vs. baked samples did not differ for white or purple potatoes. We observed dose dependent (2.5–10 μg/ml) suppression (P ≤ 0.05) of proliferation and induction (P ≤ 0.05) of apoptosis with PA in CSCs with functioning p53. Attenuation of p53 expression by shRNA in CSCs did not affect the efficacy of the PA in suppression (P ≤ 0.05) of proliferation and elevation (P ≤ 0.05) of apoptosis. These results indicate that PA acts on CSCs with the same efficacy as that of HCT‐116 and HT‐29 colon cancer cell lines, thus providing an opportunity to develop an evidence‐based dietary intervention against colon cancer. We are currently evaluating the effect of PA on colon stem cells in vivo.

Grant Funding Source: National Research Initiative Grant 2009–55200‐05197 from the USDA National Institute for Food and Agriculture (2009–2012) and Agricultural Experiment Station (AES) grant (2010–2012), Colorado State University.
Effects of a high fat/High fructose diet on brain mitochondria are counteracted by cinnamon in stressed rats
Authors: Batandier Cecile , Poulet Laurent , Canini Frederic , Couturier Karine , Hininger‐Favier Isabelle , Anderson Richard A , Roussel Anne‐Marie
Published: June 2021

High fat/high fructose diet‐(HF/HF) induced insulin resistance (IR) and stress are factors that may lead to changes in brain mitochondrial functions. We have shown previously that cinnamon (CN) and aqueous cinnamon extracts improve IR in animals and humans. In this study, we investigated the effects of CN, added to a HF/HF diet, on brain mitochondria of stressed rats. Eight groups of 10 rats were fed for 12 weeks with (i) HF/HF diet, (ii) HF/HF plus 20g CN/kg of diet (HF/HF+CN), (iii) control diet (C), (iv) C diet plus CN (C+CN) and submitted or not to an acute restraint stress just before sacrifice. In brain extracts, we measured mitochondrial calcium retention capacity, AKT and GSK3‐β (PI3‐ K signalling pathway, Western blot) and oxygen consumption. In C group, stress led to increased Ca2+ retention capacity (+40 %) that was blunted in HF/HF rats (+13 %) and restored (+30%) in HF/HF+CN group. Consistent with these data, in stressed rats, the significant increase in GSK3‐β and the same trend in AKT induced by HF/HF diet, were counteracted by CN. These results suggest that CN counters the negative effects of a HF/HF diet on brain mitochondria and could be neuro protective in stress conditions. (Funded by French PNRA 007 and USDA/ARS/USA).
Mothers’ Reasons for and Perceptions of Human Milk Expression and Feeding: A longitudinal, qualitative investigation
Authors: Felice Julia P , Rasmussen Kathleen M , Olson Christine M
Published: June 2021

A majority of breastfeeding women in the U.S. use human milk expression (HME), or pumping, to feed human milk (HM) to their babies. Yet, little is known about the reasons and strategies for HME, mothers’ perceptions of HME, and how HME fits with HM feeding and other feeding choices. We used qualitative methods to explore these issues. We recruited 20 socio‐demographically diverse pregnant women who were planning to breastfeed and considering HME. We conducted in‐depth, semi‐structured qualitative interviews in late pregnancy, early postpartum, and at other times in the first year. Interviews were transcribed and themes were identified with content analysis. Mothers used HME for several reasons, such as difficulty feeding at the breast, to allow HM feeding while at work, to facilitate bonding with family members, and to maintain or increase milk supply. Mothers perceived pumps to be less efficient than infants at emptying breasts, and HME as time‐consuming, costly, and unpleasant, but necessary to meet HM feeding goals. Bottled HM was used as an occasional stand‐in for feeding at the breast or as a major method of HM feeding. Bottled HM was rarely fed by mothers themselves. The reasons and strategies for HME and the feeding of bottled HM vary and may influence how “breastfeeding” is conducted. Given the importance of breastfeeding, these phenomena must be further explored. Funded by NIH (T32DK007158) and USDA (Hatch 399449).
Dietary C20–22 ω3 PUFA regulate hepatic oxidized PUFA levels and attenuate markers of diet induced non‐alcoholic steatohepatitis (NASH) in Ldlr−/− mice
Authors: Depner Christopher M. , Bohren Kurt M , Morin‐Kensicki Elizabeth , Jump Donald B
Published: June 2021

Non‐alcoholic steatohepatitis (NASH) is a progressive form of fatty liver disease that is characterized by hepatic inflammation, oxidative stress and fibrosis. The capacity of eicosapentaenoic acid (20:5ω3; EPA) and docosahexaenoic acid (22:6ω3; DHA) to attenuate diet‐induced NASH was examined in Ldlr−/− mice fed a western diet (WD) for 16 weeks. The WD induced severe hepatosteatosis, inflammation (Mcp1), oxidative stress (NADPH oxidase, Nox2), and fibrosis (Procol1α1). The WD also increased hepatic ω6 PUFA (i.e., arachidonic acid, 20:4ω6) & COX/LOX derived oxidized PUFA (oxPUFA, i.e., 6‐keto‐PGF1α; 12‐HETE). Mice fed the WD containing EPA or DHA had decreased expression of NASH markers (Mcp1, Nox2, Procol1α1), hepatic ω6 PUFA & ω6 oxPUFA, but increased hepatic content of ω3 PUFA & oxPUFA, i.e., EPA, DHA, 18‐HEPE & 17,18‐DiHETE. 18‐HEPE is a resolvin E‐series precursor and 17,18‐DiHETE is an epoxide hydrolase product of 17,18 epoxy‐eicosatetraenoic acid; these are cytoprotective fatty acids. We speculate that oxidized products of hepatic C20–22 ω3 PUFA metabolism play a role in the ω3 PUFA attenuation of inflammation, fibrosis and oxidative stress in WD‐induced NASH in Ldlr−/− mice.

Grant Funding Source: NIFA/USDA (2009–65200‐05846) and NIH (DK 094600 and DK043220)
Blueberry supplementation improves memory in middle aged mice consuming a high fat diet
Authors: Carey Amanda N , Shukitt‐Hale Barbara
Published: June 2021

Consuming a high fat (HF) diet may result in behavioral deficits similar to those observed in aging animals, possibly because of increased brain inflammation and oxidative stress. Our lab has demonstrated that diets supplemented with polyphenolic‐rich berries, such as blueberries (BB), can allay behavioral deficits associated with aging. Thus, supplementation of a HF diet with BB may offer protection against these putative HF diet‐related declines. Nine month old C57Bl/6 mice were maintained on one of four diets for a 5 mo period: low fat (LF) (Harlan, TD.08806, 10% calories from fat), LF + 4% BB (freeze‐dried extract, U.S. Highbush Blueberry Council), HF (TD.06414, 60% calories from lard fat), and HF + 4% BB. Mice were tested with the novel object recognition memory task after 2, 3, and 4 mo on the diets and in the Morris water maze (MWM) for spatial memory after 5 mo on the diets. Recognition memory was impaired by HF diet, but BB‐supplementation prevented recognition memory deficits in a time‐dependent manner. Probe trial performance in the MWM was impaired in animals consuming the HF diet, while animals on the HF + BB diet were not different from those on LF diets. Brain tissue is being analyzed for markers of inflammation. The goal of the study is to begin to determine if making small changes to a poor diet, like incorporating more nutrient dense foods, can allay cognitive dysfunction associated with consumption of a HF diet. Supported by USDA Intramural
Evaluation Of Antioxidant Defense In Patients Undergoing Minor Elective Surgery With Balanced Anesthesia Maintained With The Inhaled Isoflurane
Authors: Braz Mariana Gobbo , Salvadori Daisy , Braz Leandro , Braz José Reinaldo , Tang Guangwen , Yeum Kyung‐Jin
Published: June 2021

It is suggested that invasive surgical procedure can induce oxidative stress. However, only a few data regarding elective surgeries and the adjuvant effect of anesthesia are available. Fifteen patients without comorbidities, aged 18–45 years old, and scheduled for septoplasty or tympanoplasty, received general anesthesia maintained with the volatile isoflurane anesthetic. Blood samples were collected before and at the end of anesthesia. Total antioxidant performance (TAP), that measures the oxidizability of both aqueous and lipid compartments of plasma, was evaluated by fluorometry and plasma antioxidants carotenoids, tocopherols and retinol were determined by a high performance liquid chromatography (HPLC) system. Most of the carotenoids significantly decreased as well as alpha‐tocopherol and retinol (p<0.001), whereas TAP was increased (p<0.002) at the end of anesthesia. In vitro experiment revealed that this anesthetic showed an antioxidant potential in the equivalent concentration of blood during anesthesia in dose‐dependent manner. Thus, the current study indicates that despite of the decrease of some lipophilic endogenous antioxidants during balanced anesthesia with isoflurane in patients undergoing minor elective surgeries, the antioxidant activity of isoflurane itself may be resulted in increases of plasma TAP in these patients.

Supported by FAPESP, Brazil #2010/05611–0 and USDA/USA #58–1950‐7–07
Maternal obesity leads to an inflammatory response and insulin resistance in ovarian tissuse
Authors: Ruebel Meghan Lynne , Shankar Kartik , Badger Thomas , Andres Aline
Published: June 2021

Maternal obesity during the pre‐conception period may influence ovarian functions and affect embryo development. Lean and obese (OB) Sprague‐Dawley dams were examined during the preimplantation period at dpc 4.5. Obesity was induced by controlled overfeeding (40% excess calories for 28 d) via total enteral nutrition. Hormonal and metabolic parameters and ovarian gene expression were assessed. OB dams (n=7) had significantly higher body weight, greater fat mass and lesser lean mass compared to lean dams (n=10). OB dams also displayed elevated serum concentrations of triglycerides, total cholesterol, NEFA, insulin, leptin, and CCL2 (p<0.05) compared to lean dams. Microarray analysis of ovaries showed that obesity led to a down regulation of 226 genes and an up regulation of 58 genes, with an increase of several pro‐inflammatory chemokines and cytokines and down‐regulation of insulin‐regulated pathways. Confirmation by real‐time qPCR indicated elevated ovarian expression of CCL2, CXCL10, and CXCL11 (p<0.05) and decreased expression of GLUT4 (p<0.05) in OB dams compared to lean dams. In conclusion, increased maternal adiposity was associated with inflammation and reduced glucose transport in the ovaries, which may lead to dysfunction of the follicular environment and possibly impact oocyte and embryo development.

Grant Funding Source: USDA‐ARS CRIS# 6251–51000‐005–02S‐3
Effect of Pentoxifylline and Losartan on insulin resistant equine digital vessels
Authors: Venugopal Changaram S. , Holmes Earnestine , Koch Catherine , Kearney Michael , Eades Susan
Published: June 2021

Insulin response on normal blood vessel is a relaxation. However, insulin produces contraction in insulin‐resistant (IR) vessels. IR has been associated with equine laminitis. The objective of this study was to evaluate the effectiveness of two potential drugs (Losartan & Pentoxifylline) to counteract the responses of experimentally induced‐insulin resistant equine digital vessels to insulin in vitro. Palmar digital arteries and veins (2″ long) were collected from lean horses (overnight fasting plasma insulin 65pmol/L and glucose 5.614mmol/L) immediately after euthanasia. Eight 3‐mm wide rings were cut (4 arterial and 4 venous) and were set in in‐vitro tissue baths for response studies. Two rings from each vessel type were made IR by incubating them with insulin at a concentration of 10−5M for 30 min. The other rings were used as control. Then all these rings were contracted with phenylephrine 10−6.5M and when it reached a plateau either losartan (10−5M) or pentoxifylline (10−5M) was added to both insulin resistant and non resistant (control) rings and allowed to stay in the bath for 5 minutes, before a single dose of insulin (10−5M) was added to all rings. The response to insulin was monitored for another 30 minutes. Losartan pre‐treatment of IR vessels produced contraction to insulin. On the contrary, pentoxifylline caused relaxation suggesting it could be beneficial in the treatment of equine laminitis. The study was supported by USDA 1433 Formula ‐ LSU‐SVM.
Effect of Azelnidipine in Human Internal Mammary Artery and Clinical Implications
Authors: Gao Ge , BAI Xiao‐Yan , XUAN Chao , LIU Xiao‐Cheng , JING Wen‐Bin , YANG Qin , HE Guo‐Wei
Published: June 2021

Graft spasm remains challenging in coronary artery bypass grafting (CABG) surgery. We investigated the inhibitory effect of a dihydropyridine calcium antagonist azelnidipine on the vasoconstriction mediated by potassium chloride (KCl) and U46619 in human internal mammary artery (IMA) from patients undergoing CABG. Isolated IMA rings (n = 68, taken from 28 patients) were studied in organ baths in two ways: the relaxing effect of azelnidipine on vasoconstrictor‐induced precontraction by KCl and U46619 and the depressing effect of azelnidipine on the contraction. Azelnidipine caused full relaxation in KCl‐contracted (96.5% ± 0.7%) and in U46619‐contracted (96.5% ± 1.4%) IMA rings (n = 8) with 28.8‐fold higher potency to KCl than to U46619 (EC50: −7.49 ± 0.21 vs −6.03 ± 0.11 log M, p < 0.01). Pretreatment of IMA with plasma concentrations of azelnidipine (−6.1 log M) significantly depressed subsequent contraction to KCl (from 25.8 ± 2.2 mN to 16.0 ± 1.5 mN, p < 0.05) and U46619 (from 30.6 ± 4.0 mN to 16.5 ± 2.2 mN, p < 0.01). We conclude that in human IMA azelnidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of azelnidipine in CABG patients is favored in treating and preventing graft spasm.

Supported by NSF 81170148, 2010CB529500, 2009DFB30560, 09ZCZDSF04200, 10JCYBJC26400, 2012‐BH110004, 2011BHKZ001 & 2011BHKY002, and CUHK4789/09, China.
Cytoskeletal inhibitor disruption of tunneling nanotube mediated communication may affect cancer progression
Authors: Connor Yamicia Doyasi , Bhatia Sonya , Gill Navjot Kaur , Tekleab Sarah , Bharat Divya , Sengupta Shiladitya
Published: June 2021

Effective cancer therapy relies heavily on robust drug combinations. Our previous studies establish the advantage of 3D co‐culture model systems to study cancer‐promoting mechanisms. Here, we describe a model combining primary breast epithelial cells, HMEC, with a highly metastatic breast epithelial cell line, MDA‐MB‐231. We have identified a mode of communication between these cell types through thin cytoskeletal projections called tunneling nanotubes (TNTs). TNTs may promote cancer progression through rapid and specific transfer of cytoplasmic contents to neighboring cell populations resulting in transformation of previously healthy cells. TNTs form quickly (~1.5hrs) mediating transfer of intercellular contents to 35% (p<0.0001) of the primary cell population after 24hr co‐culture. The TNTs are composed of cytoskeletal components and are inhibited by low dose actin and tubulin small molecule inhibitors. Combination of 500pM Docetaxel with 30nM Latrunculin A or 50nM Cytoclasin D resulted in a 3× (p< 0.01) disruption of TNT structures, reducing TNT‐mediated communication by 33.14% (p<0.001) and 61.96% (p<0.0001), respectively. In conclusion, TNTs present a novel mechanism for breast cancer progression, inhibited by actin‐tubulin small molecule inhibitors. Therefore, low dose dual combination actin tubulin inhibitors are strong candidates for breast cancer therapies. Supported by DoD BCRP.
Voluntary activity is blunted following undernutrition in early life
Authors: Fiorotto Marta L. , Scull Brooks , Davis Teresa A , Fleischmann Ryan
Published: June 2021

We investigated if undernutrition (UN) in the neonatal period of the mouse has any long‐term impact on activity following nutritional rehabilitation. Newborn pups born to control dams were cross‐fostered to dams fed either a low protein (8 % casein) or a control (CON; 20% casein) diet. On postnatal (PN) d 22 female offspring (n=18–20/diet) were weaned to the CON diet and individually housed in metabolic cages for measurement of energy expenditure, food intake, and ambulatory cage activity until PN43; half the mice also had access to free running wheels (FW). Body wt and composition (by QMR) were measured at PN22 and PN43. At PN22 and PN43, body wt of UN pups were 75% and 88% those of CON (P<0.001) and not alterd by FW. Lean gain as % body wt gain was greater in FW than sedentary (SED) pups and similar in UN and CON mice. Daily running distance increased with age, but UN pups ran only 46% the distance of CON pups (P<0.001); the difference was greater at PN43 than PN22 (P<0.02). Ambulatory activity was unaffec ted by preweaning UN and was greater in FW than SED pups (P<0.01). Differences in food intake and energetic efficiency could not account for the difference in FW running between groups. UN in early life reduces voluntary running, but not ambulatory, activity, and this response is not reversible upon nutritional rehabilitation. (Supported by NIH AR46308 and USDA/ARS 6250–51000‐054)
Adipocytokines and fetal fat accretion in pregnant teens
Authors: Whisner Corrie Marie , Pressman Eva K , Young Bridget E , Cooper Beth E , Queenan Ruth A , O'Brien Kimberly O
Published: June 2021

Shifts in energy metabolism required for fetal development are mediated by adipokines; this process may be uniquely altered in pregnant teens undergoing continued growth across pregnancy. To assess hormonal factors of fetal fat accretion, maternal and cord blood were obtained in 171 pregnant teens (age 13–18 y). Fetal biometry and fetal abdominal wall thickness (FetalAbFat), a measure of fetal subcutaneous fat, were obtained from sonograms. Leptin and adiponectin were analyzed in maternal serum at mid‐gestation and delivery and in cord blood. Of the teens studied, 68% were Black and 32% were Caucasian; mean gestational weight gain (GWG) was 17.3 ± 8.1 kg. FetalAbFat at late gestation (34.7 ± 2.7 wks; range 26.9 – 41.0 wks) averaged 0.47 ± 0.14 cm; mean birth weight (BW) at delivery was 3322.5 ± 480.9 g. Maternal leptin and adiponectin did not differ by race but cord adiponectin was significantly (P<0.001) greater in Caucasian neonates. FetalAbFat was not linked with maternal or cord adiponectin (n=50 maternal‐neonatal pairs) but a positive trend (P=0.07, n=112 maternal‐neonatal pairs) was observed for cord leptin. Infant BW was positively related with cord leptin (P<0.0001), cord adiponectin (P<0.03) and FetalAbFat (P<0.001). In spite of GWG similar to adult women, teens often suffer lower BWs suggestive of a need for more data on determinants of fetal growth and fat accumulation in pregnant adolescents.

Grant Funding Source: USDA/NIFA Grant No. 2012–67012‐19815, 2005–35200
Medium chain triglycerides dose‐dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease
Authors: Ronis Martin , Baumgardner January , Sharma Neha , Vantease Jamie , Ferguson Matthew , Tong Yudong , Wu Xianli , Cleves Mario , Badger Thomas
Published: June 2021

To determine if there was a beneficial effect of dietary medium chain triglycerides (MCT) on nonalcoholic fatty liver disease (NAFLD), male rats were isocalorically overfed diets containing 10–70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20–65% for 21 d using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum ALTs were elevated (P<0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P<0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P<0.05). Increasing the proportion of MCT‐enriched saturated fat resulted in a dose‐dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8–C10 FAs into liver lipids, but increasing dietary MCT reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA beta‐and omega‐oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)alpha and appeared to increase mitochondrial respiration through complex III. These data suggest that dietary MCT could be utilized as a potential treatment for NAFLD. Supported in part by USDA, ARS‐CRIS 6251–51000‐005–004S.
Arginine production & nitric oxide synthesis in pregnancy, a study in Jamaican, American and Indian women
Authors: Karnes Jeffrey Mark , Hsu Jean W. , Tang Grace J. , Baker Tameka M. , Thame Minerva M. , Dwarkanath Prathiba , Kurpad Anura V. , Jahoor Farook
Published: June 2021

Arginine (arg) supply is critical for a successful pregnancy because of its roles in protein, nitric oxide (NO) and creatine syntheses and in cell growth and differentiation. NO is especially important for vascular expansion in pregnancy and a deficiency of arg supply could underlie the high prevalence of low birth weight (LBW) neonates in Indian women and in adolescent girls. Stable isotope tracers were used to measure arg flux and NO synthesis in pregnant American, Indian and Jamaican women and teenagers.

Gestation
Jamaica
India
United States

Weeks
Adult N=8
Teen N=8
Norm. BMI N=10
Low BMI N=10
Adult N=6

Arg Flux (μmol/kg/h)

13
108±6a
107±6a
50±2b
63±3b

20

108±5a

28
114±12a
82±7a
45±2b
50±2b

36–39

82±3

Post‐partum

73±6

Values are Mean±SEM;

versus postpartum value, P<0.01

lower than Jamaican and American values, P<0.01

Except for normal BMI Indian women, NO synthesis was not different among groups at trimesters 1 and 3. Pregnant Indian women produced arg at a slower rate compared to all others. This slower arg flux was associated with slower NO synthesis in normal BMI, but not in low BMI Indian women. There were significant correlations between birth weight and arg flux at trimester 1 (r=0.54, P<0.01) and trimester 3 (r= 0.53, P<0.01), indicating a strong association between decreased arg flux and LBW. Not surprisingly, the Indian women delivered 45% LBW babies compared to 19% for Jamaicans.

Grant Funding Source: USDA/ARS
Block periodization training in Navy Seal Operators: effect of 12 weeks on salivary hormones
Authors: Oliver Jonathan , Zimmer Anthony C , Wood Dallas , Abt John P , Sell Timothy C. , Lephart Scott M
Published: June 2021

We sought to determine the stress response to block periodization training (BPT) in Navy SEAL Operators by measuring salivary hormones over a 12 week period. Eighteen Navy SEAL Operators (31 ± 6 yrs, 86.6 ± 9.0 kg, 176.2 ± 5.9 cm, 17.5 ± 6.5% fat) participated in a 12 week BPT during routine operational training. Salivary free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), and cortisol (C) were obtained at four time points separated by 4 weeks coincident with changes in rest:work ratio: 1‐ prior to training (T1),2‐ moderate rest:moderate intensity (T2), 3‐ short rest:moderate intensity (T3), 4‐ long rest:high intensity (T4). The ratios of FT:C and DHEAS:C were also calculated. A significant increase in FT was observed at T3 (20.3 ± 31.4%; p < 0.05). DHEAS increased at T2 (23.2 ± 46.6%) with a further increase observed at T3 (57.0 ± 73.7%; p < 0.05). A significant increase in C was observed at T3 (20.8±41.8%; p < 0.05). No significant changes were observed in FT:C ratio. The ratio of DHEAS:C increased at T2 (45.5 ± 88.5%) with a further increase observed at T3 (43.9 ± 82.6%; p < 0.05). These data suggest that despite participation in operational training, a BPT produces acute elevations in anabolic hormones congruent with changes in intensity in SEAL Operators. Supported by ONR #N00014–11‐1–0929.
Effects of in‐utero heat stress on post‐natal thermoregulation
Authors: Johnson Jay Steven , Ross Jason , Selsby Joshua , Boddicker Rebecca , Lucy Matthew , Safranski Tim , Rhoads Robert , Baumgard Lance
Published: June 2021

Heat stress related issues will become more of a burden as climate models predict that the frequency, intensity and duration of heat waves will increase. Study objectives were to determine the extent in which in‐utero hyperthermia affects post‐natal phenotypic responses to a heat load. We hypothesized that pigs exposed to inutero HS would be more thermo‐tolerant during post‐natal development. Pregnant sows were exposed to thermoneutral (TN; constant 19 – 22°C) or HS (cyclic 28 – 38°C) conditions. Barrows from gestational TN (GTN; 73.0 ± 1.5 kg BW; n = 12), and gestational HS (GHS; 69.7 ± 1.1 kg BW; n = 12) were maintained in TN conditions (21.5°C; n = 6 GTN, n = 6 GHS) or constant HS conditions (34°C; n = 6 GTN, n = 6 GHS). Pigs in HS conditions had increased rectal temperature (Tre) and respiration rate (RR; 0.3°C and 40 bpm; P < 0.01, respectfully), compared to TN pigs. During post‐natal HS, no gestational differences in RR existed (P >; 0.10); however, GHS pigs had increased (0.2°C; P < 0.01) Tre compared to GTN pigs. Post‐natal HS decreased feed intake (26%; P < 0.01), and average daily gain tended (P < 0.07) to decrease (25%), but neither post‐natal variable was influenced by gestational treatments. These data indicate that in‐utero HS alters post‐natal thermoregulation, and appears to allow for greater tolerance (from a productivity standpoint) of increased body temperatures. Supported by USDA/NIFA Grant no. 2011–67003‐30007.
The effects of hypoxic development on cardiac function in fetal chickens
Authors: Jonker Sonnet S , Crossley Dane A
Published: June 2021

Direct measurements of cardiac function and the impact of hypoxic incubation in late stage fetal chickens have not been previously quantified, while systemic effects have been extensively documented. Given reported cardiac enlargement in hypoxic incubated fetal chickens, we sought to investigate potential changes in cardiac function that may accompany this phenotype.

METHODS

White leghorn fetal chickens were incubated at 21% (N) or 15% oxygen (H) for 19 days. Anesthetized animals from both groups had left ventricular (LV) output measured with a Transonic flow probe, or had a 3.5mm Scisense ADVantage catheter inserted to measure LV pressure‐volume relationships at 21% and 10% O2 during aortic occlusions. RNA expression was measured by quantitative PCR. Data are presented as mean±SEM.

RESULTS

Heart weight proportionate to body weight was higher in the H group (6.6±0.3 vs. 5.6±0.2, p<0.05). At 21% O2, stroke volume was lower in the H than the N group (16±2μl vs. 32±4, p<0.05). Pressure‐volume characteristics were similar between groups. Key genes in cardiac growth pathways were upregulated by hypoxic incubation (cyclin D1 160% of N, p21 240%, Notch1 200%, p<0.05), as was expression of collagens 1α2 and 3α1 (229% and 213%, p<0.05).

CONCLUSION

Intracardiac pressure‐volume parameters can be measured in chick fetuses at day 19 of incubation. Hypoxic incubation changes cardiac function and activates growth and differentiation pathways. The results reflect adaption to hypoxia in the fetus, the long‐term consequences of which are uncertain.

Supported by funding from NSF IOS‐0845741, NIH K12HD043488 & NIH 1R011HD071068.
Micro‐CT measured tracheal changes in the metathoracic femur of developing American locusts
Authors: Marti Kayla L , Rapoff Andrew J , Kirkton Scott D
Published: June 2021

In support of the hypothesis that larger insects have more oxygen delivery problems, older/larger grasshoppers have more abdominal respiratory structures. However, it is unclear if they also have more femoral respiratory structures because the anaerobic capacity of the jumping muscle increases during development. Disarticulated adult and juvenile femurs were dried overnight and placed individually in the scanning chamber of a SkyScan 1074 micro‐computed tomography unit. Images were reconstructed into transverse cross sections using computer software. Transverse sections at “stations” 20% (closest to the thorax), 40% and 60% (closest to the knee) of the length along each femur were analyzed. Near the thorax, the adult femur has three dorsal tracheae, a pair of ventral tracheae and a medial trachea. The adult dorsosagittal and dorsomedial tracheae merge at the 30% station; the ventral tracheae merge and the medial trachea vanishes at the 50% station. Near the thorax, the juvenile femur includes a single central trachea. We found tracheae void fractions to increase about 50% along the adult femur and to decrease about 50% along the juvenile femur. Void fractions were similar between adult and juvenile at the 40% station. These results suggest that older/larger grasshoppers have proportionally more respiratory structures in the distal portion of the jumping leg. Supported in part by NSF DUE 0511287 (AJR).