scholarly journals Discordant Dose-Dependent Metabolic Effects of Eicosapentanoic Acid in Diet-Induced Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1342
Author(s):  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Emily K. Miller ◽  
Hanna Davis ◽  
Shane Scoggin ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Serum Insulin ◽  
Metabolic Effects ◽  
Obese Mice ◽  
Metabolic Phenotyping ◽  
Metabolic Outcomes ◽  
High Doses ◽  
Dose Dependent ◽  
Study Dose ◽  
Lowered Body

Obesity is a widespread epidemic that increases the risk for several metabolic diseases. Despite several beneficial health effects of eicosapentaenoic acid (C20:5n-3, EPA), previous studies have used very high doses of EPA. In this study, dose-dependent effects of EPA on metabolic outcomes were determined in diet-induced obese mice. We used B6 male mice, fed high-fat diet (HF, 45% kcal fat) or HF diet supplemented with 9, 18, and 36 g/kg of EPA-enriched fish oil for 14 weeks. We conducted metabolic phenotyping during the feeding period, and harvested tissues and blood at termination. Only mice fed 36 g/kg of EPA significantly (p < 0.05) lowered body weight, fat content and epididymal fat pad weight, compared to HF. Both 18 and 36 g/kg doses of EPA significantly increased glucose clearance and insulin sensitivity, compared to HF or 9 g/kg of EPA. Locomotor activity was significantly increased with both 18 and 36 g/kg doses of EPA. Interestingly, all doses of EPA compared to HF, significantly increased energy expenditure and oxygen consumption and significantly reduced serum insulin, leptin, and triglycerides levels. These results demonstrate weight- and adiposity-independent metabolic benefits of EPA, at doses comparable to those currently used to treat hypertriglyceridemia.

Dose‐Dependent Anti‐Inflammatory and Metabolic Effects of Eicosapentaenoic Acid in Diet‐Induced Obese Mice

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Mandana Pahlavani ◽  
Hanna Davis ◽  
Emily Miller ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
...  
Keyword(s):  
Eicosapentaenoic Acid ◽  
Metabolic Effects ◽  
Obese Mice ◽  
Anti Inflammatory ◽  
Dose Dependent

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

Prophylactic Effects of Metoprolol on the Prevention of Atrial Fibrillation after Cardiac Surgery Are Dose Dependent

2014 ◽  
Vol 17 (1) ◽  
pp. 54 ◽  
Author(s):  
Nan Cheng ◽  
Changqing Gao
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Surgery ◽  
Heart Surgery ◽  
Beta Blockers ◽  
Open Heart Surgery ◽  
Asian Patients ◽  
Different Response ◽  
Prolonged Hospital ◽  
Dose Dependent ◽  
Study Dose

Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. Many studies have reported an incidence of 20%-40% in patients undergoing open heart surgery, and the peak incidence usually occurs between the postoperative days [Fuller 1989; Aranki 1996; Svedjeholm 2000; Maisel 2001]. AF is commonly self-limited and rarely results in postoperative death. However, postoperative AF (POAF) is often associated with complications, including stroke, heart failure, prolonged hospital stay, and increased costs [Maisel 2001; Bramer 2010]. Many pharmacological methods have been used to prevent this complication, and beta-blockers, which have been investigated in several studies, have demonstrated effectiveness [Ali 1997; Connolly 2003; Crystal 2004; Halonen 2006; Imren 2007]. There is currently a consensus in the use of beta-blockers for the prevention of POAF. However, whether the effect of beta-blockers on POAF is dose dependent has not been widely studied [Coleman 2004; Lucio 2004]. In addition, patients with different racial backgrounds have a different response to metoprolol based on body shape. In addition, the CYP2D6 genotypes are different among white and Asian patients. In this study dose-dependent prophylactic effects of beta-blockers, which were obtained in a single center.

scholarly journals Association between breakfast skipping and metabolic outcomes by sex, age, and work status stratification

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jun Heo ◽  
Won-Jun Choi ◽  
Seunghon Ham ◽  
Seong-Kyu Kang ◽  
Wanhyung Lee
Keyword(s):  
Regression Analysis ◽  
Negative Binomial ◽  
Metabolic Diseases ◽  
Young Male ◽  
Negative Binomial Regression ◽  
Final Analysis ◽  
Work Status ◽  
Breakfast Skipping ◽  
Metabolic Outcomes ◽  
Binomial Regression

Abstract Background The association between breakfast skipping and abnormal metabolic outcomes remains controversial. A comprehensive study with various stratified data is required. Objective The aim of this study was to investigate the relationship between abnormal metabolic outcomes and breakfast skipping by sex, age, and work status stratification. Methods We used data from the Korea National Health and Nutrition Examination Surveys from 2013 to 2018. A total of 21,193 (9022 men and 12,171 women) participants were included in the final analysis. The risk of metabolic outcomes linked to breakfast skipping was estimated using the negative binomial regression analysis by sex, work status, and age stratification. Results A total of 11,952 (56.4%) participants consumed breakfast regularly. The prevalence of abnormal metabolic outcomes was higher among those with irregular breakfast consumption habits. Among young male workers, negative binomial regression analysis showed that irregular breakfast eaters had a higher risk of abnormal metabolic outcomes, after adjusting for covariates (odds ratio, 1.15; 95% confidence interval, 1.03–1.27). Conclusions The risk of abnormal metabolic outcomes was significant in young men in the working population. Further studies are required to understand the association of specific working conditions (working hours or shift work) with breakfast intake status and the risk of metabolic diseases.

EFFECT OF INTRAVENTRICULAR ADMINISTRATION OF NORADRENALINE ON WATER DIURESIS IN GOATS

1975 ◽  
Vol 66 (3) ◽  
pp. 375-383 ◽  
Author(s):  
G. VANDEPUTTE-VAN MESSOM ◽  
G. PEETERS
Keyword(s):  
Intraventricular Administration ◽  
Excretion Ratio ◽  
Dose Response Relationship ◽  
Water Diuresis ◽  
3Rd Ventricle ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
High Doses ◽  
Excretion Rates ◽  
Dose Dependent

SUMMARY During water diuresis in conscious goats, noradrenaline (NA), its antagonists phentolamine, phenoxybenzamine and propranolol and also atropine were administered into the 3rd ventricle. The subsequent effects on water diuresis and on the excretion rates of Na+, K+ and Cl− were investigated. Infusion of NA into the 3rd ventricle induced a strong and significant antidiuretic response and a decrease in the Na+: K+ excretion ratio; these effects were dose-dependent. High doses of NA produced a significant increase in urinary K+ excretion. Similar results were observed after i.v. administration of arginine-vasopressin. Pretreatment with phentolamine injected into the 3rd ventricle produced a dose-dependent inhibition of the NA-induced antidiuretic effects. Phenoxybenzamine also blocked the response to NA but a dose-response relationship was not apparent. Atropine and propranolol did not block the response to NA.

scholarly journals The metabolic effects of a commercially available chicken peri-peri (African bird’s eye chilli) meal in overweight individuals

2015 ◽  
Vol 117 (5) ◽  
pp. 635-644 ◽  
Author(s):  
Jacolene Kroff ◽  
David J. Hume ◽  
Paula Pienaar ◽  
Ross Tucker ◽  
Estelle V. Lambert ◽  
...  
Keyword(s):  
Core Body Temperature ◽  
Resting Energy Expenditure ◽  
High Sensitivity ◽  
Normal Glucose Tolerance ◽  
Metabolic Effects ◽  
Microvascular Reactivity ◽  
Reactive Protein ◽  
Metabolic Outcomes ◽  
Normal Glucose ◽  
Hs Crp

AbstractA growing body of evidence suggests that capsaicin ingestion may lead to desirable metabolic outcomes; however, the results in humans are equivocal. Whether or not benefits may be gained from ingestion of capsaicin via a commercially available meal has not been determined. The objectives of this randomised, cross-over intervention study were to compare the 2 h postprandial effects of a standard commercially prepared meal containing chilli (HOT, 5·82 mg total capsaicinoids) with a similar meal with no chilli (CON, <1·0 mg total capsaicinoids) on resting energy expenditure, plasma insulin, glucose, serum high sensitivity C-reactive protein (hs-CRP) concentrations, core body temperature and forearm microvascular reactivity responses in overweight individuals. A total of thirty-four apparently healthy individuals (sixteen men and eighteen women) between 18 and 50 years of age, with a BMI >25 kg/m2 and a waist circumference >94 cm (men) or 80 cm (women), were studied. Participants had normal glucose tolerance and were accustomed, but were not regular chilli eaters. A paired t test indicated that insulin AUC was smaller following the HOT meal (P=0·002). Similarly, there was a tendency for glucose AUC to be reduced following the HOT meal (P=0·056). No discernable effects of the HOT meal were observed on metabolic rate, core temperature, hs-CRP concentrations and endothelial-dependent microvascular reactivity. The results from this study indicate that a standard restaurant meal containing a relatively small dose of capsaicin delivered via African bird’s eye chilli, which is currently available to the public, results in lower postprandial insulin concentrations in overweight individuals, compared with the same meal without chilli.

Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 691-705 ◽  
Author(s):  
C. Tickle ◽  
A. Crawley ◽  
J. Farrar
Keyword(s):  
Retinoic Acid ◽  
Gap Junctions ◽  
Time Course ◽  
Apical Ectodermal Ridge ◽  
Threshold Response ◽  
Epithelial Morphology ◽  
Early Effects ◽  
High Doses ◽  
Columnar Cells ◽  
Dose Dependent

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139–169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.

Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats

1995 ◽  
Vol 269 (3) ◽  
pp. R662-R668 ◽  
Author(s):  
T. Ando ◽  
T. Ichijo ◽  
T. Katafuchi ◽  
T. Hori
Keyword(s):  
Prostaglandin E2 ◽  
Sympathetic Nerve ◽  
Time Course ◽  
Sympathetic Nerve Activity ◽  
Dependent Manner ◽  
Central Administration ◽  
Nerve Activity ◽  
High Doses ◽  
Alpha Chloralose ◽  
Dose Dependent

The effects of central administration of prostaglandin E2 (PGE2) and its selective agonists on splenic sympathetic nerve activity (SNA) were investigated in urethan- and alpha-chloralose-anesthetized rats. An intra-third-cerebroventricular (13V) injection of PGE2 (0.1-10 nmol/kg) increased splenic SNA in a dose-dependent manner. An I3V injection of an EP1 agonist, 17-phenyl-omega-trinor PGE2 (1-30 nmol/kg), also resulted in a dose-dependent increase in splenic SNA, with a time course similar to that of PGE2-induced responses. In contrast, EP2 agonists, butaprost (10-100 nmol/kg I3V) and 11-deoxy-PGE1 (10-100 nmol/kg I3V), had no effect on splenic SNA. An I3V injection of M & B-28767 (an EP3/EP1 agonist, EP3 >> EP1) increased splenic SNA only at high doses (10-100 nmol/kg). Pretreatment with an EP1 antagonist, SC-19220 (200 and 500 nmol/kg), completely blocked the responses of splenic SNA to PGE2 (0.1 nmol/kg) and M & B-28767 (10 nmol/kg), respectively. These findings indicate that brain PGE2 increases splenic SNA through its action on EP1 receptors.

Lateral hypothalamus and sympathetic firing rate

1988 ◽  
Vol 255 (3) ◽  
pp. R507-R512 ◽  
Author(s):  
T. Sakaguchi ◽  
M. Takahashi ◽  
G. A. Bray
Keyword(s):  
Firing Rate ◽  
Lateral Hypothalamus ◽  
Sympathetic Nerves ◽  
Hypothalamic Area ◽  
Interscapular Brown Adipose Tissue ◽  
Gold Thioglucose ◽  
Brown Adipose ◽  
Bilateral Lesions ◽  
Dose Dependent ◽  
Lowered Body

Measurements of sympathetic firing rate have been made after the acute microinjection of glucose or insulin into the lateral hypothalamic area as well as after ablation of this area with locally injected gold thioglucose. Injection of glucose into the lateral hypothalamus (LH) produced a small but significant and dose-dependent reduction in the firing rate of efferent sympathetic nerves to interscapular brown adipose tissue. Injection of insulin into the same region produced a very short-lived increase in efferent sympathetic firing rate. Bilateral lesions in the lateral hypothalamus produced by microinjection and gold thioglucose lowered body weight more than sham injections into the LH of control animals. There was an increase in basal sympathetic firing rate at 3, 9, and 24 h after LH lesions. There was also an increase in firing rate at 1 and 3 days, but by 7 days firing rate had returned to control levels. The data support the hypothesis that LH lesions enhance sympathetic activity but show only very limited modulation by glucose or insulin.

Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures

2004 ◽  
Vol 17 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Merav Kedmi ◽  
Arthur L. Beaudet ◽  
Avi Orr-Urtreger
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Mutant Mice ◽  
Wild Type ◽  
Nicotinic Acetylcholine ◽  
Nocturnal Frontal Lobe Epilepsy ◽  
Wide Range ◽  
High Doses ◽  
Dose Dependent ◽  
Rate Of Response

Nicotine, the main addictive component of tobacco, evokes a wide range of dose-dependent behaviors in rodents, and when administrated in high doses, it can induce clonic-tonic seizures. Nicotine acts through the nicotinic acetylcholine receptors (nAChRs). Mutations in the human α4- and the β2-nAChR subunit genes cause autosomal dominant nocturnal frontal lobe epilepsy. Using transgenic mice with mutations in nAChR subunits, it was demonstrated previously that the α4-, α5-, and α7-subunits are involved in nicotine-induced seizures. To examine the possibility that the β4-subunit is also involved in this phenotype, we tested mice with homozygous β4-subunit deficiency. The β4 null mice were remarkably resistant to nicotine-induced seizures compared with wild-type and α5 null mice. We also generated mice with double deficiency of both α5- and β4-nAChR subunits and demonstrated that they were more resistant to nicotine’s convulsant effect than either the α5 or the β4 single mutant mice. In addition, the single α5 mutants and the double α5β4-deficient mice exhibited a significantly shorter latency time to seizure than that of the wild-type mice. Our results thus show that β4-containing nAChRs have a crucial role in the pathogenesis of nicotine-induced seizures. Furthermore, by comparing multiple mutant mice with single and double subunit deficiency, we suggest that nicotinic receptors containing either α5- or β4-subunits are involved in nicotine-induced seizures and that receptors containing both subunits are likely to contribute to this phenomena as well. However, the α5-subunit, but not the β4-subunit, regulates the rate of response to high doses of nicotine.

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