bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous Vascular and Sweating Responses to Intradermal Administration of Prostaglandin E1 and E2 in Young and Older Adults: a Role for Nitric Oxide?
Authors: Fujii Naoto , Singh Maya Sarah , Halili Lyra , Boulay Pierre , Sigal Ronald J , Kenny Glen P 
Published: November 2023

Cyclooxygenase (COX) contributes to cutaneous vasodilation and sweating responses, however the mechanisms underpinning these responses remain unknown. We hypothesized that prostaglandin E1 (PGE1) and E2 (PGE2), which are COX‐derived products, directly mediate cutaneous vasodilation and sweating through nitric oxide synthase (NOS)‐dependent mechanisms in young adults. Furthermore, we hypothesized that this response is diminished in older adults, since ageing attenuates COX‐dependent cutaneous vasodilation and sweating. In 9 young (4 males and 5 females, 22 ± 5 years) and 10 older (3 males and 7 females, 61 ± 4 years) adults, cutaneous vascular conductance (CVC, laser‐Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were measured at four intradermal forearm skin sites receiving incremental doses (0.05, 0.5, 5, 50, 500 μM each for 25 min) of PGE1 or PGE2 with and without co‐administration of 10 mM L‐NNA, a non‐specific NOS inhibitor. L‐NNA attenuated PGE1‐mediated increases in CVC in young adults, while it attenuated PGE2‐mediated increases in CVC in older adults (all P < 0.05). However, the magnitude of the PGE1‐ and PGE2‐mediated increases in CVC did not differ between groups (all P > 0.05). Neither PGE1 nor PGE2 increased sweat rate at any of the administered concentrations for either the young or older adults (all P > 0.05). We show that the cutaneous vasodilator response is mediated through NOS‐dependent mechanisms albeit via PGE1 in young adults and PGE2 in older adults, respectively. We also show that cutaneous vascular responsiveness to PGE1 and PGE2 is similar between young and older adults. Lastly, in both young and older adults, we show that both PGE1 and PGE2 do not directly increase sweat rate.Support or Funding InformationThis study was supported by the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014), and by Canada Foundation for Innovation (Leaders Opportunity Fund, 22529) (funds held by Dr. Glen P. Kenny).
Ablation of eNOS Does Not Promote Adipose Tissue Inflammation
Authors: Jurrissen Thomas J , Sheldon Ryan D , Gastecki Michelle L , Zidon Terese M , Rector R. Scott , Vieira‐Potter Victoria J , Padilla Jaume 
Published: November 2023

Adipose tissue (AT) inflammation is a hallmark characteristic of obesity and an important determinant of insulin resistance and cardiovascular disease; therefore, a better understanding of factors regulating AT inflammation is critical. It is well established that reduced vascular endothelial nitric oxide (NO) bioavailability promotes arterial inflammation; however, the role of NO in modulating inflammation in AT remains disputed. In the present study, ten‐week old C57BL6 wild‐type and eNOS knockout male mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat, 17% sucrose, and 1% cholesterol) for 18 weeks (n=7–8/group). In wild‐type mice, Western diet‐induced obesity led to increased visceral white AT expression of inflammatory genes (e.g., MCP1, TNFα, CCL5 mRNAs) and markers of macrophage infiltration (e.g., CD68, ITGAM, EMR1, CD11C mRNAs and Mac‐2 protein), as well as reduced markers of mitochondrial content (e.g., oxphos complex I and IV protein). These effects of Western diet on visceral white AT were not accompanied by decreases in eNOS activation. eNOS knockout mice, independent of the diet, were leaner and did not exhibit greater white or brown AT inflammation compared to wild‐type mice. Collectively, these findings do not support the hypothesis that reduced NO signaling contributes to obesity‐related AT inflammation.Support or Funding InformationThis work was supported by a University of Missouri Life Sciences Fellowship (R. D. Sheldon), Veterans Health Administration grant CDA2 BX001299 (R. S. Rector), and National Institute of Health grants K01 HL‐125503 and R21 DK‐105368 (J. Padilla).
Adipose Inflammation and Cardiovascular Disease Risk Factors in Obesity‐Prone Osborne‐Mendel and Obesity‐Resistant S5B/Pl Rats
Authors: Primeaux Stefany , Souza‐Smith Flavia , Poret Jonquil , Mouton Alan , Marcell Shawn , Battle Claire , Braymer H. Douglas , Harrison‐Bernard Lisa 
Published: November 2023

Obesity‐related increases in visceral adipose deposition and inflammation, circulating triglyceride (TRG), LDL cholesterol, and C‐reactive protein (CRP) enhance the risk for CVD. These effects may be intensified by the consumption of an energy dense, high fat diet (HFD). The current study tested the hypothesis that HFD consumption would exacerbate CVD risk factors in obesity‐prone Osborne‐Mendel (OM) rats, compared to obesity‐resistant S5B/Pl (S5B) rats. OM and S5B rats were fed either a HFD (60% fat; n=6/strain) or low fat diet (LFD, 10% fat; n=6/strain) for 7 weeks. A multiplex rat cytokine/chemokine panel was used to assess the expression of inflammatory markers in epididymal fat and subcutaneous fat depots. Circulating TNF‐α and CRP levels were determined by ELISA and circulating TRG, HDL, LDL and total cholesterol were assessed. Cardiac hypertrophy was assessed by total heart and left ventricular mass. As expected, body weight, % visceral adiposity (OM‐HFD 5.3% vs. S5B‐HFD 1.2%) and adipocyte size were increased by HFD intake to a greater extent in the obesity‐prone OM rats. Higher basal levels of IL‐6, TNF‐α, IL‐1α, and IL‐1β were detected in the epididymal fat depots of obesity‐prone rats. Consumption of a HFD increased Il‐6, TNF‐α, IL‐1α, and IL‐1β in the epididymal fat of both OM and S5B rats. HFD intake synergistically increased TNF‐α expression in OM rats (2‐fold vs. S5B‐HFD; p<.05). However, circulating levels of TNF‐α were decreased in OM rats fed the HFD. In subcutaneous fat, HFD intake did not alter inflammatory marker expression in either OM or S5B rats, though basal expression of IL‐6, IL‐1α, and IL‐1β was higher in subcutaneous fat of OM rats, compared to S5B rats (p<.05). Circulating TRG was increased and HDL cholesterol was decreased in OM rats, regardless of diet. Circulating CRP levels were increased by HFD in both strains, suggesting an inflammatory response to the HFD (p<.05). Left ventricle/heart ratio was lower in OM rats, but increased with HFD consumption in this strain, suggesting cardiac hypertrophy. A HFD‐induced increase in pro‐inflammatory cytokine expression in the visceral adipose depot, but not in subcutaneous fat, supports the role of visceral fat in the deleterious effects of dietary fat. Higher basal levels of pro‐inflammatory cytokines in adipose tissue and TRG and lower levels of HDL cholesterol in obesity‐prone rats suggest that this strain is at a greater risk for developing CVD compared to the obesity‐resistant rats.Support or Funding InformationCOBRE 1P30GM106392
Predicting Metabolic Syndrome Risk Factors Using Different Anthropometric Indices Of Obesity In A Farm Worker Population, Western Cape South Africa
Authors: Nell Theo A , Kruger Maritza J 
Published: November 2023

Anthropometric assessments can be used in epidemiological field studies to assess health status. The prevalence of both the metabolic syndrome(MetS) and obesity are on the increase in the South African population, thus increasing the risk of developing lifestyle related diseases including diabetes, cardiovascular disease, and cancer. The farm worker population in the Western Cape Province are also now included in this increased prevalence. Using anthropometrical indices, such as body mass index (BMI), waist circumference (WC), and waist to hip ratio (W:H) in epidemiological field studies, could possibly increase the risk prediction of the metabolic syndrome as well as obesity.This cross‐sectional study included both men and women (total n= 188; n= 147 women and n=41 men) which revealed a total metabolic syndrome prevalence of 42.6%. The women in this sample had a 46% prevalence compared to the men (29%). We then wanted to distinguish the association between anthropometrical indices and the metabolic syndrome risk factors for both genders, irrespective of their metabolic status.We reported that the women showed significant correlations for all the metabolic syndrome risk factors with the following anthropometrical indices; BMI, WC and W:H. This was not seen for the men where BMI, WC and W:H only significantly correlated with high density lipoprotein cholesterol(HDL‐c), glucose (Gluc), triglycerides (TG), and diastolic blood pressure (DBP). Since the women seemed to have a higher risk for the metabolic syndrome we further subdivided only the women into either the metabolic syndrome (IDF criteria) versus non‐metabolic syndrome groups.In the metabolic syndrome group, W:H was only significantly correlated with TG (r=0.32; p=0.007) and Gluc (r=0.39;p=0.001), whilst, BMI was significantly correlated with systolic blood pressure(SBP) (r=0.39; p=0.001) and DBP (r=0.31; p=0.001). Waist circumference was only significantly correlated with SBP (r=0.35; p=0.003).For the non‐metabolic syndrome group, only W:H significantly correlated with TG (r=0.43; p=0.000).The BMI, WC and W:H may be better predictors of the metabolic syndrome in the female group, however, when this group were subdivided this was no longer evident. Here, the W:H and BMI indices were better predictors of only certain risk factors.Support or Funding InformationThis study was funded by the Cancer Association of South Africa (CANSA)
Soybean Oil High Fat Diet Reduces Hypothalamic Oxytocin Immunoreactivity
Authors: Ho Catherine , Deol P. , Richardson H. , Platt D. , Yang E. , Jiang T. , Sladek F. M. , Curras‐Collazo M. 
Published: November 2023

It is well established that the intake of fatty foods induces obesity, although relatively little attention is given to the type of fat. Male mice fed a high fat diet (HFD) rich in saturated fat had significantly less weight gain, adiposity, glucose intolerance and fatty liver as compared to mice fed a high fat diet containing soybean oil (SO), rich in the polyunsaturated omega‐6 fatty acid linoleic acid (LA‐HFD) or a diet rich in a genetically modified, low LA soybean oil (PL‐HFD). Both LA‐HFD and PL‐HFD also have similarly higher levels of the phytosterol, stigmasterol, than HFD. The adverse effects of SO may be mediated, in part, by brain oxytocin, although this has not been studied. Oxytocin is anorexigenic and mouse models of obesity show reduced brain Oxt. Here we examined the effect of SO diet on oxytocin. Male C57BL/6N mice were fed for 17–27 weeks either vivarium chow (VC) or one of 4 iso‐caloric diets: HFD (coconut oil), LA‐HFD (SO), PL‐HFD (GM SO) or Stigma‐HFD (coconut oil with same amount of stigmasterol as LA‐ and PL‐HFD) or control (VC). Immunoreactivity (IR) to an antibody specific for oxytocin‐neurophysin in the paraventricular nucleus of the hypothalamus was markedly lower in LA‐, PL‐ and Stigma‐HFD groups relative to HFD and VC. Similar but less marked differences were obtained in arcuate nucleus. For the supraoptic nucleus a similar pattern was observed except that oxytocin IR in PL‐HFD was not reduced (n=5–6 experiments, 3–5 animals per group). Our findings demonstrate that the stigmasterol can decrease paraventricular oxytocin and this may help explain the obesity and diabetic propensity associated with a diet rich in SO.Support or Funding InformationSupport: APS fellowships (C.H., D.P.), UCR UGR Student Mini‐Grant (C.H), NIEHS T32 fellowship (P.D.) and Collaborative grant, UCR ORED (F.S., T.J. and M.C.C.).
Stress and stretch of alveolar sacs and the influence in the CO2 transport
Authors: Caucha Luis Jhony , Cruz Julio Cesar , Rubio Obidio 
Published: November 2023

Caucha's et al. (FASEB J. 2010, 24:1063.5) showed that the alveolar dilution of CO2 becomes more evident with the forced expiration and reveals the effect of CO2 diffusion from RV to ERV, in the expired forced maneuver (efm). Now, we are interested in simulating the accumulation of CO2 in the alveolar sacs when it is filling with room air in the efm. The alveolar geometry was taken from a terminal sac with five alveoli, where CO2 exchanges from blood to alveoli. The place where in the 23 generations in the base region of the lung. Using the Navies‐Stokes and convection diffusion equations for CO2, we simulated the fluid dynamics in these alveolar sacs and quantified the stress‐stretch in the wall and the accumulations of CO2 for different volumes in the same time of respiration. The expansion for a normal and forced maneuver were 9 and 90%, respectively, with respect to initial position. The difference for CO2 was 73×10−3 ml from the normal to forced maneuver, the stress in the wall, for a normal maneuver, changed following the pattern of respirations, like a sinusoidal curve, but in a forced maneuver, the stress did not follow the same pattern. In conclusion, the amount of CO2 in the alveolar sacs, depends upon the number of capillaries in the wall and it is not affected by the efm.Support or Funding InformationSupported by PNICP (Programa Nacional de Innovaciòn para la Competitividad y Productividad)
Loss of the Persistent Sodium Current Elicits Homeostatic Plasticity in Respiratory Rhythm Generation
Authors: Baertsch Nathan Andrew , Ramirez Sanja Corina , Ramirez Jan Marino 
Published: November 2023

The neural networks underlying the generation of breathing rhythms must remain stable and dynamic throughout the lifetime of an organism. In many neural networks, it is hypothesized that mechanisms of homeostatic plasticity regulate synaptic and/or intrinsic properties of neurons to maintain stability. The neural network giving rise to the inspiratory phase of breathing, termed the preBötzinger Complex (preBötC), utilizes a combination of intrinsic membrane conductances, such as the persistent sodium current (INaP) and the nonspecific cation current (ICAN), as well as synaptic properties to generate and shape the inspiratory rhythm. When isolated in brainstem slices, the preBötC continues to produce remarkably stable rhythmic population activity in phase with inspiratory motor output. We hypothesized that homeostatic mechanisms within the preBötC maintain stability of the inspiratory rhythm. Slices containing the preBötC were incubated overnight (~16hrs) in 10μM DNQX or 20μM riluzole to block excitatory synaptic transmission or the persistent sodium current, respectively. Upon washout, we observed that DNQX did not significantly alter the inspiratory rhythm. However, in slices incubated with riluzole, inspiratory burst amplitude was increased and frequency was decreased compared to controls (ACSF only). To explore this finding further, rhythmic activity was recorded for the duration of the riluzole exposure. Following ~30–40min, riluzole perturbed the rhythm such that inspiratory frequency dramatically slowed or stopped. Surprisingly, after ~7hrs the rhythm came back spontaneously, indicating plasticity had occurred to overcome the loss of INaP. The rhythm and burst shape were altered such that amplitude and burst rise slope were increased (~300% and 220% baseline, respectively) and frequency was slowed (~30% baseline). Following thorough washout of riluzole (1–3hrs), the new large and slow inspiratory pattern remained, suggesting long lasting changes in network properties had occurred. In a subset of preBotC slices, riluzole was reapplied following washout. In contrast to naïve slices, there was no effect on inspiratory frequency following >1hrs in riluzole, indicating that the new rhythm was insensitive to loss of INaP. However, burst amplitude was reduced suggesting INaP remained present in preBötC neurons. These studies demonstrate that the preBötC can compensate for long‐lasting changes in network properties with mechanisms of homeostatic plasticity and begin to provide a basis for understanding how the neural networks underlying breathing rhythms may adapt to maintain stability in health and disease.Support or Funding InformationNIH RO1 HL 126523
Cross‐talk interactions between spinal 5‐HT7 and 5‐HT2A receptors regulate serotonin‐induced phrenic motor plasticity
Authors: Fields Daryl Pinion , Mitchell Gordon 
Published: November 2023

Spinal serotonin receptors elicit respiratory motor plasticity, expressed as a long‐lasting enhancement in respiratory motor output; i.e. phrenic motor facilitation (pMF). While serotonin type 2 (5‐HT2A) and 7 (5‐HT7) receptors elicit phenotypically similar pMF, they do so via distinct cellular mechanisms. We previously demonstrated that low‐doses of serotonin give rise to pMF via 5‐HT2A receptors, but cross‐talk inhibition from 5‐HT7 receptors abolish pMF at higher doses indicating a “bell shaped” dose‐curve response for serotonin‐induced pMF. Thus, 5‐HT7 receptors both give rise to and constrain pMF. We have recently identified cAMP as a critical point of divergence for these contrasting effects. Specifically, 5‐HT7 receptors constrain 5‐HT2A receptor‐induced pMF via protein kinase A (PKA), but elicit pMF via exchange protein activated by cAMP (EPAC). Our working hypothesis is that selective activation of these divergent cAMP signaling pathways enables refined regulation of serotonin‐induced pMF. Further, we hypothesized that coincident 5‐HT2A receptor and EPAC activation would enhance pMF, whereas 5‐HT2A and PKA activation would constrain/eliminate pMF expression. In anesthesized, paralyzed and mechanically ventilated rats, intermittent intrathecal injections of a 5HT2A receptor agonist (DOI; 50.6 ± 3.1%; p ≤ 0.05) or EPAC activator (8pCPT; 6.2 ± 16.7%; p ≤ 0.05) alone elicited pMF; concurrent EPAC and 5‐HT2A receptor activation gave rise to additive pMF (110.9 ± 10.0%; p ≤ 0.05). In contrast, while PKA activator (6Bnz) alone gave rise to pMF (58.9 ± 8.6%; p ≤ 0.05), concurrent PKA and 5‐HT2A receptor activation abolished the capacity for either to elicit pMF (18.6 ± 6.5%; p ≥ 0.05). Thus, divergent cAMP signaling exerts contrasting effects on serotonin‐induced respiratory motor plasticity. Targeting of these distinct signaling pathways may be useful for treating diseases causing motor deficits, including spinal injury or motor neuron diseases.Support or Funding InformationSupported by NIH HL080209 and HL69024. DPF was supported by an Advanced Opportunity Fellowship at the University of Wisconsin, NIH fellowship (1F30HL126351‐010) and the Medical Scientist Training Program (NIH T32 GM008692).
Short‐chain fatty acids, 4‐phenylbutyric acid and R‐alpha‐lipoic acid, improve mTORC1‐driven overproduction of apoB‐containing triacylglyceride‐rich lipoproteins
Authors: Moreau Regis , Roberts Joseph L. , He Bo , Erickson Anjeza 
Published: November 2023

The activation of hepatic kinase mechanistic target of rapamycin complex 1 (mTORC1) is implicated in the development of obesity related metabolic disorders. This study investigated the metabolic sequelae of mTORC1 hyperactivation in hepatocytes and the lipid‐regulating mechanisms of 4‐phenylbutyric acid (PBA) and R‐alpha‐lipoic acid (LA). We created three stable cell lines that exhibit low, normal or high mTORC1 activity. mTORC1 hyperactivation induced the expression of lipogenic (DGAT2, +229%) and lipoprotein assembly (MTP, +130%; APOB, +220%) genes thereby raising cellular triacylglyceride (TG, +27%) and secretion of apoB‐containing lipoproteins (+124%). LYS6K2, a specific inhibitor of the p70 S6 kinase branch of mTORC1 signaling, reversed these effects. PBA and LA decreased secreted TG through distinct mechanisms. PBA repressed apoB expression (mRNA, −38%; protein, −46%) and lowered secreted TG (−26%) without mitigation of mTORC1 hyperactivity or activation of AMPK. LA significantly decreased cellular (−27%) and secreted (−46%) TG by attenuating mTORC1 signaling independently of AMPK. LA did not regulate apoB expression but led to the secretion of TG‐poor lipoproteins via repression of lipogenic genes, (FASN, −70%; DGAT2, −81%), and upregulation of CPT1A (+319%). Our studies provide new mechanistic insight into the hypolipidemic activity of PBA and LA.Support or Funding InformationSupported by UNL Hatch Act, Tobacco Settlement Funds, and Layman Seed Award.
Innovations in course design to facilitate understanding, retention, and application of Regulation of Macronutrient Metabolism
Authors: Thalacker‐Mercer Anna , Vanderlan Rob 
Published: November 2023

RationaleRegulation of Macronutrient Metabolism is a core graduate nutrition course. While students meet the course requirements for the Nutritional Sciences Graduate Program, many students are several years from their undergraduate degree and/or need reinforcement in foundational knowledge necessary for comprehension of graduate level macronutrient metabolism material. Students do not come to class prepared to build on or apply foundational knowledge, expecting to receive first exposure to course material in lecture. Further, students then learn the material in preparation for assessments. This type of learning strategy minimizes both understanding and opportunities to apply knowledge in lectures and discussions; students are unable to appropriately apply course materials in class discussions. It is well‐recognized that students (i) better retain material taught using flipped‐classroom methods and (ii) achieve higher order learning outcomes when presented with opportunities to apply knowledge. Lastly, student opportunity for reviewing and disseminating nutritional science research is limited, but important for post‐graduate careers. Recognizing the necessity of locking knowledge on macronutrient metabolism into long‐term memory and the need for engaged active learning, the following are the course design objectives for Regulation of Macronutrient Metabolism to meet the learning outcomes: (i) Facilitate better understanding of core material. (ii) Bring in‐class material together with contemporary macronutrient metabolism literature. (iii) Develop professional skills related to dissemination of nutrition education and research.Course design(i) Provide short, online videos and assessments that review foundational concepts for understanding macronutrient metabolism (e.g., biochemistry, physiology, molecular and cellular biology) and are essential for comprehension of in‐class lectures and participation in group discussions. (ii) Utilize in‐class activities in addition to traditional lectures. Examples in‐class activities include small and large group discussions of contemporary research related to macronutrient metabolism and analysis, interpretation, and discussion of translational research in macronutrient nutrition (i.e. bench to bedside and farm to community). (iii) A final project will consist of either a written critical review or a delivered short lecture on a topic in contemporary macronutrient metabolism research. Throughout the semester students will complete scaffolded assignments building toward the final project. The final project will not only improve the application and retention of knowledge, but will also build professional skills necessary for post‐graduate careers. Students will be evaluated based on online assessments, in‐class activities, and the final project.