bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single residue substitution confers thiazide sensitivity to the European eel thiazide‐resistant NaCl cotransporter, NCCb isoform
Authors: Vega‐Mateos Antonio , Moreno Erika , Plata Consuelo , Vazquez Norma , Pacheco‐Alvarez Diana , Gamba Gerardo 
Published: June 2021

The thiazide sensitive Na‐Cl cotransporter (NCC) is the major pathway for salt reabsorption in the distal convoluted tubule of the mammalian kidney and is the receptor for the thiazide diuretics, which constitute one of the baseline therapies for arterial hypertension worldwide. Yet, the binding site for thiazides at the NCC is still unknown. In the eel the NCC gene is duplicated. The NCCα is an orthologue for mammalian NCC and is expressed at the eel's kidney, while the duplicated gene, the NCCβ is expressed along the intestine and is not present in mammals. We recently reported that the NCCβ of the European eel (eNCCβ) is a thiazide‐resistant NaCl cotransporter (Moreno et al, JBC 2016).Here, we used “clustal omega” software to analyze all the NCC sequences known to this moment and compared them to the eNCCβ, searching for residues that are conserved in all NCCs, except in the eNCCβ. Using site‐directed mutagenesis we substituted specific amino acid residues in the sequence of eNCCβ, for those that are highly preserved in all other NCC sequences. The mutant cDNAs were sequenced to avoid unwanted mutations. Assessment of the functional expression was performed in Xenopus laevis oocytes, microinjected with cRNA from the wild‐type and mutated eNCCβ, by measuring the tracer 22Na+ uptake in the absence or presence of extracellular chloride or of hydrochlorothiazide.Sixteen different amino acid residues of the eNCCβ, localized at the first seven transmembrane regions (TM), were individually substituted for the corresponding residue in rat NCC. The wild type eNCCβ cRNA injection induced after two days of incubation the expression of Na‐influx pathway that was chloride dependent, but not affected by thiazide diuretics, up to 10‐3 M concentration. In 15 out of 16 mutant clones, NaCl transport activity was present, but no thiazide sensitivity was observed. However, the substitution of a phenylalanine for a tyrosine at the position 174 (eNCCβ‐F174Y), which is localized at the extracellular loop that binds TM1 to TM2, conferred over 90% of inhibition with hydrochlorothiazide, with an IC50 of about 10‐7 M. In addition, the tracer 22Na+ uptake induced by eNCCβ‐F174Y was inhibited by five different thiazide diuretic tested, but not by furosemide.A substitution of a phenylalanine for tyrosine residue at position 174 of the eel NCCβ isoform confers sensibility to thiazide diuretics in the eel NCCβ cotransporter.Support or Funding InformationSupported by Conacyt grant numbers 222918 and 188712 to EM and GG, respectivelyThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
SEX‐SPECIFIC HORMONES PRODUCED DURING PROESTROUS AND ESTROUS EXERT A REGULATORY EFFECT ON NESFATIN‐1 MRNA LEVELS AND AUTONOMIC FUNCTION IN FEMALE CYCLING RATS
Authors: Pate Alicia Nicole , Schnell Abigayle L. , Samson Willis K , Yosten Gina LC 
Published: June 2021

Nesfatin‐1/NUCB2 is a protein derived from the nucleobindin‐2 precursor originally localized in different appetite controlling areas of the brain, such as the hypothalamic PVN, ARC, SON, LHA and NTS, and is thought to be regulated in a sex‐specific manner. It has recently been suggested that nesfatin‐1 might play an important metabolic role during pregnancy and fetal development (2) and the expression of nesfatin‐1/NUCB2 is regulated by progesterone and 17b‐estradiol in mouse pituitary gland (1). We investigated Nesfatin‐1 mRNA expression in female, cycling rats across the estrous cycle and observed a decrease in Nesfatin‐1 mRNA during Proestrous, corresponding to a period of increased levels of Estradiol. We therefore hypothesized that the ability of centrally administered Nesfatin‐1 to raise mean arterial pressure (MAP) in conscious, cycling, freely moving female rats would no longer be seen during the Proestrous day of the estrous cycle. We, therefore, monitored MAP changes across estrous cycle with central Nesfatin‐1 administration. We found that the ability of Nesfatin‐1 to increase MAP is no longer prevalent in female, cycling rats on proestrous and estrous days. We then monitored MAP changes in ovariectomized females with and without estradiol supplementation. We found that the ability of Nesfatin‐1 to increase MAP is no longer prevalent in female rats that were pretreated with estradiol, suggesting that sex‐specific hormones produced during proestrous and estrous exert a regulatory effect on the Nesfatin‐1 mRNA levels and autonomic function.Support or Funding InformationThis work was funded through a President's Research Fund grant (Saint Louis University) to GLCY. WKS and GLCY are supported by a grant from the National Institutes of Health, HL‐121456This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of maternal obesity on body weight regulation and sleep time in offspring
Authors: Moak Sydney P. , Dai Xuemei , Hall John E. , da Silva Alexandre A. , do Carmo Jussara M. 
Published: June 2021

Mississippi Center for Obesity Research, University of Mississippi Medical Center – Jackson, MS. There is limited understanding of the mechanisms that link parental obesity to adverse metabolic outcomes in their offspring. In this study we examined factors that influence body weight regulation and sleep time in mice fed a high fat diet after weaning (HFD, n=5) that were offspring of dams also fed a HFD (45% fat) and compared them to HFD fed mice (n=5) from dams on a control diet. Food intake was measured daily and body weight and body composition (EchoMRI) were measured weekly. Energy expenditure (EE), oxygen consumption (VO2), motor activity (MA) and sleep time (Sable System 40 sec criterion) were monitored for 5 consecutive days at 22 weeks of age. There were no significant differences in calorie intake (17.3±0.7 vs. 16.2±0.8 kcal/day), fasting blood glucose (170±13 vs. 187±16 mg/dL), total EE (5.7±0.6 vs. 5.7±0.2 kcal/hr), VO2 (1.5±0.1 vs. 1.7±0.1 ml/min) or MA (57±6 vs. 65±5 m/day) in offspring from dams fed a HFD compared to offspring from dams fed a control diet. However, there were significant increases in body weight (47.3±1.5 vs. 42.4±1.1 g) and fat mass (19.8±0.6 vs. 15.7±1.6 g), and decreased sleep time (8.6±0.2 vs. 9.7±0.2 hr/day, p=0.005) in offspring of dams fed a HFD. These results suggest that maternal obesity increases body weight and fat mass in offspring fed a HFD, and reduces sleep time without altering food intake, VO2, EE, MA, or fasting glucose levels in adult mice (NHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428)Support or Funding InformationNHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Interrelationships among perceived stress, food addiction, and body mass index
Authors: Lin Yi‐Syuan , Yeh Jhih‐Han , Chien Yi‐wen 
Published: June 2021

The degree of perceived stress affects the emotional response of humans, leads to behavioral changes, and is more likely to trigger physical illness. Many studies have indicated that the level of stress and amount of stressors are related to overeating and unhealthy eating behavior, which will cause obesity in the long run. According to the statistics in Ministry of Health and Welfare, the number of visits for mentally stressful diseases in Taiwan has doubled year by year, and adults who are overweight and obese have continued to grow after reaching 43% in 2014. An assumption about whether perceived pressure is a factor affecting the obesity has made and whether food addiction is posing as an intermediate factor has yearn more and more attention in oversea studies. Therefore, the purpose of this study is to explore whether perceived stress affects the development of food addiction and body mass index. The study was conducted through online questionnaire, composed of the basic data form, the Perceived Stress Scale, the Beck Depression Inventory‐Short Form and the Yale Food Addiction Scale. We analyzed 1019 valid questionnaire. The results showed 132 participants met the food addiction criteria, accounting for 12.95% of the total sample. Among them, there were 54 overweight and obese people, accounting for 40.91% of the food addiction participants. Moreover, there were 22 people with mild depression among the samples meeting the food addiction criteria, 54 with moderate depression and 42 with severe depression, in which presented as proportion of 16.67%, 40.91% and 31.82%. By dividing the sum score of the perceived stress scale with the quartile method, 83.3% of the food addiction sample met the top quartile. The study expects that perceived stress level is positively correlated with the prevalence of food addiction, food addiction is positively correlated with BMI, and those with higher perceived stress but lower degree of depression have greater tendency of food addiction and greater BMI values than those with higher perceived stress and higher degree of depression.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex differences in the physiological response to coconut oil based high fat diets in C57BL/6J mice
Authors: Sitnick Mitchell , Wang Shari , den Hartigh Laura J 
Published: June 2021

It is well established that diets containing a high percentage of calories from fat leads to a myriad of metabolic issues from obesity, insulin resistance, and diabetes to an impaired skeletal muscle growth response. With the growing percentage of individuals considered overweight or obese, it is of critical importance that we understand the effect of fats on human physiology. One response to the rise in obesity is an increased promotion of products believed to promote weight management. This is true in the case of coconut oil. Products containing coconut oil have become popular due to a perceived benefit to human health which includes an ability to help control body weight an effect attributed to high levels of short‐ and medium‐chain fatty acids in the oil. While these classes of fatty acids on their own have been shown to be beneficial, the actual health benefits of dietary coconut oil remains unclear.In order to test the possible health benefits of coconut oil rich diets we fed both male and female, C57Bl/6J mice standard chow or a diet that contained either 10% (LFC) or 45% (HFC) kcal from coconut oil. Mice were fed for either 14 weeks or 30 weeks and multiple physiological parameters were measured. In response to the diets, preliminary analyses suggests that that while HFC led to a significant alterations in body and tissue weights compared to LFC, gender had a significant moderation effect on weight (β = −7.052, p<0.05) and other parameters (Subcutaneous fat, β =−1.926, P<0.027, Tibialis Anterior mass, β = 0.036, p<0.05).While further testing is needed, this data partially supports the idea that, in moderation, coconut oil could potentially serve as a beneficial fat source for certain populations. Further, these results provide additional evidence in support of the current initiative to account for sex as a biological variable in basic physiological studies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Saturated and Unsaturated Fat Diets Yield Different Disease Phenotypes in Mice
Authors: DeWitt Elizabeth , Dysinger Ian , Larmer Zachary , Kolwicz Stephen C 
Published: June 2021

Excessive consumption of unsaturated or saturated fatty acids have adverse effects on certain health parameters, namely increased risk of obesity, diabetes, and cardiovascular disease. Specifically, saturated fats are linked to increased cardiovascular risk while unsaturated fats are suggested to protect against cardiovascular disease. Our previous work suggested that various high fat diets have differential effects on cardiac hypertrophy and function. However, it was not clear whether a high saturated fat diet (HSFD) or high unsaturated fat diet (HUFD) could elicit different disease phenotypes. Therefore, the purpose of this study was to evaluate the effects of HSFD or HUFD on the development of obesity, diabetes, and cardiac lipotoxicity in mice. Male, C57BL/6J mice received normal chow (CON, n=12), HSFD (n=15) or HUFD (n=15) for 12 weeks. Body weight and food intake were measured weekly. After 12 weeks, the adipose tissue and heart were removed and weighed. Glucose, fatty acids, and cholesterol were analyzed in serum using biochemical assays. Cardiac triglycerides (TG) were measured in heart tissue extracts. Both HSFD and HUFD significantly increased body weight above CON. Interestingly, body weight increased by ~63% in the HUFD while the HSFD increased ~41% (P<0.05). Adipose tissue mass was increased 5‐fold in both HFD groups and was ~10% greater in the HUFD. Surprisingly, caloric intake was higher in the HSFD (15.3±0.8) compared to HUFD (12.8±0.1) and CON (11.9±0.7). Serum cholesterol levels were elevated in both HSFD and HUFD. Blood glucose was significantly increased only in the HUFD while serum fatty acids were increased only in the HSFD. Cardiac hypertrophy, assessed by the heart weight to tibia length ratio, was increased in the HSFD but not HUFD group. Cardiac TGs were ~25% higher in HSFD but <10% in HUFD compared to CON. These data show that excess consumption of saturated or unsaturated fats increased body weight and adiposity in mice. However, high consumption of unsaturated fatty acids resulted in a pronounced increase in body weight, body fat, and hyperglycemia, consistent with an obese and diabetic phenotype. Conversely, high consumption of saturated fatty acids caused elevated serum lipids, cardiac hypertrophy, and cardiac lipid accumulation, consistent with cardiac lipotoxicity. In conclusion, the fatty acid composition of diets may be critical in the development of disease phenotypes resulting from high fat feeding in mice.Support or Funding InformationThis work was supported by funding from the American Heart Association and Ursinus College.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Specific Differences in a Lipodystrophy‐induced Hypertension Mouse Model
Authors: Gatineau Eva , Su Wen , Gong Ming , Yiannikouris Frederique 
Published: June 2021

Obesity rate is higher in women than in men and is more strongly associated with hypertension in extremely obese women. However, the relative contribution of the adipose tissue itself to blood pressure control and to anti‐hypertensive drug's efficacy is not completely understood and is often difficult to assess because of its inter‐ and intra‐variability within subject and within sex.In the present study, we used a lipodystrophy‐induced hypertension mouse model, adipose prorenin receptor (PRR) KO mice, to investigate sex differences in the relative contribution of adipose tissue to hypertension and to antihypertensive drug's efficacy. Autonomic nervous system inhibitors and AT1R blockers (ARBs) were used to investigate whether the elevation of blood pressure observed in adipose PRR KO male and female mice was driven by the same mechanism. The decrease of systolic blood pressure (SBP) induced by losartan, an AT1R blocker, was exacerbated in high fat (HF)‐fed adipose PRR KO female mice compared with control female mice but not in male mice (Delta SPB: CTL male, −7.9±1.5 mmHg; KO male, − 6.4±3.1 mmHg; CTL female, −5.3±1.9 mmHg; KO female, −14.2±0.9 mmHg). In contrast, the contribution of the autonomic nervous system, assessed via injections of propranolol, atropine and chlorisondamine, revealed that the tachychardic response was significantly greater in HF‐fed adipose PRR‐KO male mice compared with control, but not in female mice (Delta heart rate: CTL male, +114.2±12.1 bpm; KO male, +156.0±11.1 bpm; CTL female, +84.8±10.1 bpm; KO female, +89.8±21.3 bpm). Together, our data indicated that SBP elevation was primarily mediated by an AngII‐dependent mechanism in HF‐fed adipose PRR‐KO female mice whereas it was mainly driven by the para‐sympathetic nervous system in HF‐fed male adipose PRR‐KO mice. The present study also suggested that the presence of an expanded adipose tissue decreased the ability of female to respond to ARBs whereas it decreased the ability of male to respond to autonomic nervous system inhibitors. Interestingly, plasma sPRR, the soluble form of PRR, is higher in female than in obese male mice (CTL: Male: 2.8 ± 0.3 ng/ml; Female: 5.1 ± 0.5 ng/ml) and in HF‐fed adipose PRR KO female than in adipose PRR KO male mice (KO: Male: 7.1 ± 0.1 ng/ml; Female: 11.6 ± 2.4 ng/ml). Whether sPRR contributes to obesity‐hypertension and to the phenotype observed in adipose PRR‐KO mice through a sex specific mechanism is currently under investigation. Together our data support the importance of personalized medicine for antihypertensive treatment choices.Support or Funding InformationNational Institutes of Health Grants (R01‐HL‐130463), American Heart Association (13SDG17230008), National Institute of General Medical Sciences (P20‐GM103527), University of Kentucky, Center for Clinical and Translational Sciences (UL1TR000117)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Maternal and Sex‐Specific Fetal Characteristics of Three Different Mouse Models for Fetal Programming by Preeclampsia
Authors: Plösch Torsten , Dijkstra Dorieke J. , Stojanovska Violeta , Verkaik‐Schakel Rikst Nynke , Scherjon Sicco A. 
Published: June 2021

Epidemiological data shows that preeclampsia increases the susceptibility for cardiovascular and metabolic diseases later in life in mother and offspring. This is usually referred to as “fetal programming” or “epigenetic programming”. However, conclusive data on causative factors and molecular mechanisms is lacking. This could potentially be examined in animal models, but preeclampsia is a multifactorial disease for which the perfect animal model does not exist. Here we compare the maternal and fetal status at the end of preeclamptic pregnancy in several mouse models, in order to unravel the mechanisms possibly involved in long‐term programming of health.We employed three C57Bl/6 mouse models mimicking specific parts of the phenotype of preeclampsia: the sFlt+LPS model, a combination of an antiangiogenic and a proinflammatory factor; the L‐NAME model, where vasoconstriction is induced; and the LXR agonist model, which is shown to induce metabolic distortion and antiangiogenesis. Interventions took place at gestational day 8 or 10. Right before delivery, at gestational day 18, we compared maternal and fetal phenotypes between the models.Elevated maternal systolic blood pressure was found in sFlt+LPS and L‐NAME dams, while to our surprise blood pressure was decreased in the LXR agonist model. Albuminurea was only found in the sFlt+LPS model. Maternal circulating insulin, an important fetal growth factor, was found decreased in the LXR agonist model, while no changes were found in free thiols, a measure of oxidative status.Consequences for fetuses were model‐ and sex‐specific. LXR agonist and sFlt+LPS fetuses were growth restricted, with brain sparing taking place in male fetuses only. Placental efficacy, as measured by body weight/placenta ratio, was lower for male LXR agonist and L‐NAME fetuses. Disturbed fetal growth is known to have long‐lasting metabolic consequences for the fetus.To conclude, we show here that different animal models for preeclampsia result in different maternal and fetal characteristics, with the sFlt+LPS model showing the most resemblance with clinical preeclampsia. A long‐term study in the sFlt+LPS model will give insight in programming effects and programming mechanisms of preeclampsia for both mother and offspring.Support or Funding InformationThis work was supported by the Netherlands Organization for Health Research and Development (ZonMW, grant number 91211053 to T.P.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex‐specific Computational Models for Blood Pressure Regulation in the Rat
Authors: Ahmed Sameed , Leete Jessica , Hernandez Francisco Lopez , Layton Anita 
Published: June 2021

Renal hemodynamics play a critical role in blood pressure regulation, while renal autoregulatory mechanisms maintain kidney function for varying blood pressure. Computational models have been developed of the cardiovascular system to simulate blood pressure regulation in humans, including the seminal model by Guyton et al. (Ann Rev Physiol 1972). Although the Guyton model and its many variants represent mechanisms for renal autoregulation, they appear to fail to adequately maintain glomerular filtration rate for a sufficiently wide range of blood pressure. Additionally, while such human models have clinical values in that they can be used to assess the effects and reveal mechanisms of hypertensive therapeutic treatments, rodent models would be more useful in assisting the interpretation of animal experiments. Finally, despite well‐known sexual dimorphism in blood pressure regulation, all published models are gender neutral Given these observations, the goal of this project is to develop the first sex‐specific computational models of blood pressure regulation for the rat. The resulting models represent the interplay between cardiovascular function, renal hemodynamics, and kidney function. They also include the actions of the renal sympathetic nerve activity and the renin‐angiotensin‐aldosterone system. We applied the models to investigate the cardiovascular effects of antihypertensive treatments including diuretics, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blocker (ARB), and of nonsteroidal anti‐inflammatory drugs (NSAIDs). Simulations were conducted to identify risks factors for acute kidney injury following the administration of a combination of these treatments.Support or Funding InformationThis research was supported by the Canada 150 Research Chair program and by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, grant R01DK106102.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.