Bulleyaconitine A Inhibits Morphine-Induced Withdrawal Symptoms, Conditioned Place Preference, and Locomotor Sensitization Via Microglial Dynorphin A Expression

Bulleyaconitine A (BAA), a C19-diterpenoid alkaloid, has been prescribed as a nonnarcotic analgesic to treat chronic pain over four decades in China. The present study investigated its inhibition in morphine-induced withdrawal symptoms, conditioned place preference (CPP) and locomotor sensitization, and then explored the underlying mechanisms of actions. Multiple daily injections of morphine but not BAA up to 300 μg/kg/day into mice evoked naloxone-induced withdrawal symptoms (i.e., shakes, jumps, genital licks, fecal excretion and body weight loss), CPP expression, and locomotor sensitization. Single subcutaneous BAA injection (30–300 μg/kg) dose-dependently and completely attenuated morphine-induced withdrawal symptoms, with ED50 values of 74.4 and 105.8 μg/kg in shakes and body weight loss, respectively. Subcutaneous BAA (300 μg/kg) also totally alleviated morphine-induced CPP acquisition and expression and locomotor sensitization. Furthermore, subcutaneous BAA injection also specifically stimulated dynorphin A expression in microglia but not astrocytes or neurons in nucleus accumbens (NAc) and hippocampal, measured for gene and protein expression and double immunofluorescence staining. In addition, subcutaneous BAA-inhibited morphine-induced withdrawal symptoms and CPP expression were totally blocked by the microglial metabolic inhibitor minocycline, dynorphin A antiserum, or specific KOR antagonist GNTI, given intracerebroventricularly. These results, for the first time, illustrate that BAA attenuates morphine-induced withdrawal symptoms, CPP expression, and locomotor sensitization by stimulation of microglial dynorphin A expression in the brain, suggesting that BAA may be a potential candidate for treatment of opioids-induced physical dependence and addiction.

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SAT-655 Bile Acid Sequestration Synergistically Accelerates Glucagon Receptor-Stimulated Body Weight Loss in Diet-Induced Obese Mice

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1106 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Teayoun Kim ◽

Shelly R Nason ◽

Jessica Antipenko ◽

Natalie Presedo ◽

Brian Finan ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Bile Acid ◽

Glucose Intolerance ◽

Body Weight Loss ◽

Farnesoid X Receptor ◽

Fecal Excretion ◽

Complete Suppression ◽

Obese Mice ◽

Glucagon Receptor

Abstract Glucagon, an essential regulator of glucose and lipid metabolism, also promotes weight loss in obese mice. We have shown that hepatic Farnesoid X Receptor (FXR, a bile acid receptor) and bile acids (BA) play an important role in the anti-obesity effect of glucagon in mice. Specifically, glucagon-receptor (GCGR) agonism is a potent regulator of BA metabolism, increasing total plasma BA levels and preferentially raising cholic and chenodeoxycholic acid levels. These findings led us to hypothesize that BA, signaling via hepatic FXR, contributes to GCGR-stimulated weight loss. Furthermore, we reasoned that BA sequestration may impair GCGR-mediated weight loss by reducing the availability of BA to stimulate FXR-action. Thus, to elucidate the role of BA in GCGR-mediated weight loss, we utilized anion-exchange BA-binding resins (BARS; Cholestyramine and Colesevelam) to prevent intestinal (ileal) re-uptake and reduce plasma total cholesterol, LDL, and BAs via fecal excretion. Diet-induced obese (DIO) C57Bl/6J mice were randomized to groups matched for body-weight and administered daily GCGR agonism (IUB288, 10 nmol/kg, s.c.) or vehicle, in the presence or absence of BARS. Consistent with our prior findings, IUB288-treatment reduced body weight in DIO mice. Counter to our original hypothesis, IUB288+Cholestyramine (3% in high fat diet, HFD [58% kcal%]) enhanced IUB288-stimulated weight loss. Similar body-weight loss effects following combined IUB288 and BARS treatment were replicated both at a lower dose of Cholestyramine (1.5% in HFD), as well as in combination with both low- (2% in HFD) and high- (4% in HFD) dose Colesevelam. IUB288-stimulated weight loss is accompanied by suppression of food intake (FI), while Colesevelam alone did not significantly lower FI at either dose (2 or 4% in HFD). However, 4% Colesevelam with IUB288 completely suppressed FI, while 2% Colesevelam stimulated a reduced, though not complete suppression. GCGR agonism is a potent stimulus of weight loss; however, its impairment of glucose tolerance reduces its value as a monotherapy. Excitingly, Cholestyramine (3% in HFD) rescued IUB288-induced glucose intolerance, restoring glucose excursion to levels observed in control (vehicle-treated) mice. Together these studies suggest BARS may enhance the anti-obesity effect of GCGR agonism, beneficially regulate feeding behaviors, and prevent GCGR-stimulated glucose dysregulation in DIO mice. Furthermore, these studies argue that GCGR agonsim combined with BARS treatment may represent a novel therapeutic approach for obesity and obesity-associated glucose intolerance.

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Effect of Chaihu-jia-Longgu-Muli decoction on withdrawal symptoms in rats with methamphetamine-induced conditioned place preference

Bioscience Reports ◽

10.1042/bsr20211376 ◽

2021 ◽

Author(s):

Zifa Li ◽

Yuchen Qi ◽

Kun Liu ◽

Yiming Cao ◽

Hao Zhang ◽

...

Keyword(s):

Body Weight ◽

Conditioned Place Preference ◽

Open Field Test ◽

Control Model ◽

Place Preference ◽

Withdrawal Symptoms ◽

Control Group ◽

Model Group ◽

Low Dosage ◽

Preference Experiment

Traditional Chinese medicine detoxification prescription Chaihu-jia-Longgu-Muli decoction (CLMD) relieves depressive symptoms in patients withdrawing from methamphetamine. In this study, we assessed the effects of CLMD on methamphetamine withdrawal in rats. A methamphetamine-intoxicated rat model was established. Rats were randomly divided into the control, model, high-dosage, medium-dosage, and low-dosage groups, receiving high, medium, and low doses of CLMD, respectively. Weekly body weight measurements revealed that rats treated with methamphetamine had the lowest body weight. The conditioned place preference experiment revealed that methamphetamine-intoxicated rats stayed significantly longer in the drug-paired chamber than the control rats. However, after administering high-dosage CLMD, the amount of time the rats spent in the drug-paired chamber was significantly less than that of the model rats. Our open-field test revealed that the model group had lower crossing and rearing scores than the control group. Additionally, rats that received CLMD treatment exhibited higher crossing and rearing scores than the model rats. Striatal DA, 5-HT, and β-EP and serum IL-1α and IL-2 concentrations were estimated. Rats in the model group had lower striatal DA, 5-HT, and β-EP and higher serum IL-1α and IL-2 concentrations than those in the control group. High-dosage CLMD administration significantly changed the concentrations of these molecules, such that they approached normal concentrations. In general, CLMD could prevent the development of methamphetamine-induced withdrawal symptoms in rats by increasing the DA, 5-HT, and β-EP and lowering the IL-1α and IL-2 concentrations.

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1965-P: Glucagon Receptor Agonism Stimulates Body Weight Loss in Antibiotic Treatment in Obese Mice

Diabetes ◽

10.2337/db19-1965-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1965-P

Author(s):

TEAYOUN KIM ◽

JESSICA P. ANTIPENKO ◽

SHELLY NASON ◽

NATALIE PRESEDO ◽

WILLIAM J. VAN DER POL ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Antibiotic Treatment ◽

Body Weight Loss ◽

Obese Mice ◽

Glucagon Receptor

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Relation between change in treatment for central diabetes insipidus and body weight loss

Minerva Endocrinologica ◽

10.23736/s0391-1977.18.02718-9 ◽

2018 ◽

Vol 44 (1) ◽

Author(s):

Ayako Ito ◽

Aya Nozaki ◽

Ichiro Horie ◽

Takao Ando ◽

Atsushi Kawakami

Keyword(s):

Weight Loss ◽

Body Weight ◽

Diabetes Insipidus ◽

Body Weight Loss ◽

Central Diabetes Insipidus

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Responder analysis of subjects achieving HbA1c reduction ≥1% and body weight loss ≥5% across SUSTAIN 1–5 clinical trials

10.26226/morressier.59d51847d462b80296ca3c25 ◽

2017 ◽

Author(s):

Ho Thien

Keyword(s):

Weight Loss ◽

Clinical Trials ◽

Body Weight ◽

Body Weight Loss ◽

Responder Analysis

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Prognostic value of body weight loss and tissue components in patients with chronic heart failure and reduced left ventricular ejection fraction

UMJ Heart & Vessels ◽

10.30978/hv2019-3-34 ◽

2019 ◽

Vol 0 (3) ◽

pp. 34-42

Author(s):

L. G. Voronkov ◽

K. V. Voitsekhovska ◽

S. V. Fedkiv ◽

V. I. Koval

Keyword(s):

Heart Failure ◽

Weight Loss ◽

Body Weight ◽

Chronic Heart Failure ◽

Left Ventricular Ejection Fraction ◽

Prognostic Value ◽

Body Weight Loss ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction

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Chemicals Causing 10% or Greater Body Weight Loss in F344 Strains of Rats

Chemical Effects in Biological Systems (CEBS) ◽

10.22427/ntp-data-022-00002-0027-000-5 ◽

2020 ◽

Author(s):

Keyword(s):

Weight Loss ◽

Body Weight ◽

Body Weight Loss

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Isoquinoline Alkaloids in Sows’ Diet Reduces Body Weight Loss during Lactation and Increases IgG in Colostrum

Animals ◽

10.3390/ani11082195 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2195

Author(s):

Ester Arévalo Sureda ◽

Xuemei Zhao ◽

Valeria Artuso-Ponte ◽

Sophie-Charlotte Wall ◽

Bing Li ◽

...

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Body Weight ◽

Body Weight Loss ◽

Muscle Thickness ◽

Passive Immunity ◽

Isoquinoline Alkaloids ◽

Back Muscle ◽

Fat Thickness ◽

And Performance

Isoquinoline alkaloids (IQ) exert beneficial antimicrobial and anti-inflammatory effects in livestock. Therefore, we hypothesized that supplementing sows’ diets with IQ during gestation would decrease farrowing stress, affecting the piglets’ development and performance. Sows were divided into: IQ1, supplemented with IQ from gestation day 80 (G80) to weaning; IQ2, supplemented from gestation day 110 (G110) to weaning, and a non-supplemented (NC) group. Sow body weight (BW), feed intake, back-fat thickness and back-muscle thickness were monitored. Cortisol, glucose and insulin were measured in sows’ blood collected 5 d before, during, and after 7 d farrowing. Protein, fat, IgA and IgG were analyzed in the colostrum and milk. Piglets were monitored for weight and diarrhea score, and for ileum histology and gene expression 5 d post-weaning. IQ-supplemented sows lost less BW during lactation. Glucose and insulin levels were lower in the IQ groups compared to NC-sows 5 d before farrowing and had higher levels of protein and IgG in their colostrum. No other differences were observed in sows, nor in the measured parameters in piglets. In conclusion, IQ supplementation affected sows’ metabolism, reducing body weight loss during lactation. Providing IQ to sows from their entrance into the maternity barn might be sufficient to induce these effects. IQ improved colostrum quality, increasing the protein and IgG content, improving passive immunity for piglets.

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