Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice

Recent studies have suggested a role for nitric oxide (NO) in the regulation of food intake. The present studies were undertaken to examine the effects of the administration of a nitric oxide synthetase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on food intake and weight loss. Two genetically obese mice, the ob/ob and db/db strains, and their lean heterozygote littermate controls, ob/c and db/c, served as subjects. In the first experiment, we demonstrated that L-NAME (100 micrograms/kg) given twice over a feeding period of 7 h/day produced a small but significant weight loss in ob/ob mice but not in their lean-genotype controls (P < 0.05). In the second experiment, a higher dose of L-NAME (100 mg/kg), given twice daily, produced a marked effect on body weight, with the ob/ob mice losing approximately 10% of their body weight in 9 days. The ob/c mice showed a lesser decrease in body weight. Food intake was decreased on all 9 days in the ob/ob mice (P < 0.01). A small decrease in body weight and food intake was seen in db/db and db/c mice receiving L-NAME. These studies provide further evidence for a role of nitric oxide in the modulation of food intake and weight gain.

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PACAP ameliorates the fertility of obese mice through PAC1/PKA/ERK/Nrf2 signal axis

Journal of Endocrinology ◽

10.1530/joe-20-0316 ◽

2021 ◽

Author(s):

Wailan Shan ◽

Shiyin Lu ◽

Biqian Ou ◽

Jia Feng ◽

Zixian Wang ◽

...

Keyword(s):

Body Weight ◽

Inflammatory Response ◽

Male Infertility ◽

Cell Model ◽

Male Reproduction ◽

Obese Mice ◽

High Fat ◽

Pac1 Receptor

Obesity is strongly linked to male infertility. Apoptotic inflammatory response caused by oxidative stress in testicular spermatogenic cells is one of the important causes of obesity-related male infertility. Pituitary adenylate cyclase activating polypeptide (PACAP) as a bioactive peptide secreted by the pituitary gland, has a powerful triple role of anti-oxidation, anti-apoptosis and anti-inflammation, and is involved in male reproduction regulation, but the specific mechanism remains unknown. The purpose of the current study is to explore the role of PACAP in obesity-related male infertility. In cell-level experiments, Mouse spermatocytes (GC-2) were treated with palmitate (PA) to establish an high-fat injury cell model in vitro and then treated with PACAP. In animal-level experiments, C57BL/6 male mice were fed with a high-fat diet (HFD) to induce obesity and then treated with PACAP. The cell mechanism studies showed that PACAP selectively binds to the PAC1 receptor to attenuate palmitic acid-induced mouse spermatogenic cell (GC-2) oxidative damage and apoptotic inflammatory response via the PKA/ERK/Nrf2 signaling axis. However, this mechanism was inhibited in GC-2 cells inhibiting the activity of Nrf2. The animal experiment studies showed that PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes/body weight, serum lipids levels, and reproductive hormone levels in vivo. Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology and sperm parameters via Keap1/Nrf2/ARE pathway. These beneficial effects of PACAP were abolished in obese mice with testis-specific knockdown of Nrf2.

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Abstract 5085: Formerly obese mice display increased mmtv-wnt-1 tumor growth despite normalization of body weight: The role of mTOR

10.1158/1538-7445.am10-5085 ◽

2010 ◽

Author(s):

Rebecca E. De Angel ◽

Rajeshwar R. Tekmal ◽

Susan N. Perkins ◽

Linda A. deGraffenried ◽

Steve D. Hursting

Keyword(s):

Body Weight ◽

Tumor Growth ◽

Obese Mice

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Abstract 397: HMOX1 Ameliorates Fatty Liver and Metabolic Syndrome by Reduction of Hepatic Heme and PGC1a

Hypertension ◽

10.1161/hyp.62.suppl_1.a397 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Komal Sodhi ◽

Wade G Douglas ◽

Stephen J Peterson ◽

Larry Dial ◽

Imran T Khawaja ◽

...

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Body Weight ◽

Blood Glucose ◽

Fatty Liver ◽

Obese Mice ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Lipid Droplet Size

Introduction: Nonalcoholic fatty liver (NAFLD) occurs in a setting of high fat diets, insulin resistance, obesity and dyslipidemia. Individuals with NAFLD have an increased risk of developing metabolic syndrome. Heme oxygenase-1 (HMOX1), a major cytoprotective enzyme, attenuates oxidative stress and obesity and increases insulin sensitivity. The antioxidant effect of HMOX1 is due to an increase in ferritin, and bilirubin and a decrease in heme, a pro-oxidant. The aim of this study was to examine the role of increased hepatic HMOX activity in decreasing steatosis, adiposity and vascular dysfunction and to determine the mechanism underlying these metabolic changes in obese mice. Methods: Obese mice were administered cobalt protoporphyrin (CoPP) and HMOX activity inhibitor stannous mesoporphyrin (SnMP) for 6 weeks. Blood pressure, body weight and blood glucose levels were measured in all the groups. Glycogen content, hepatic fibrosis, heme levels, fatty acid synthase (FAS) and lipid droplet size in liver were also assessed. Results: CoPP administration increased hepatic HMOX1 protein levels and HMOX activity, decreased blood pressure, body weight, blood glucose levels, hepatic heme content (p<0.05) as compared to obese mice. Our results also showed that HMOX1 induction causes a significant decrease in lipid steatosis ( lipid droplet size and FAS levels; p<0.01) as compared to obese mice. Densitometry analysis showed increased expression of PPARα and Glut 1 along with decreased expression of PGC1α in hepatic tissue. These beneficial effects were reversed by administration of SnMP. Conclusion: This novel study demonstrates the role of hepatic HMOX1 in attenuating the fatty liver and metabolic homeostasis by decreasing PGC1α and heme content and enhancing glycogen levels. Pharmacological agents that increase HMOX1 levels or gene targeting of HMOX1 offer a promising therapeutic target for NAFLD and suggest the existence of a significant link between the heme-HMOX system and the extent and severity of heme-dependent fatty liver.

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Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.76.1.28 ◽

2006 ◽

Vol 76 (1) ◽

pp. 28-33 ◽

Cited By ~ 7

Author(s):

Yukari Egashira ◽

Shin Nagaki ◽

Hiroo Sanada

Keyword(s):

Body Weight ◽

Urinary Excretion ◽

Enzyme Activities ◽

Treated Group ◽

Control Group ◽

Puromycin Aminonucleoside ◽

Low Level ◽

Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

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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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Recent Advances in Obesity: The Role of Turmeric Tuber and Its Metabolites in the Prophylaxis and Therapeutical Strategies

Current Medicinal Chemistry ◽

10.2174/0929867324666161118095443 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4837-4853 ◽

Cited By ~ 4

Author(s):

Agata Jarząb ◽

Wirginia Kukula-Koch

Keyword(s):

Body Weight ◽

21St Century ◽

The Body ◽

Excess Body Weight ◽

Inflammatory Reactions ◽

Drug Candidates ◽

Scientific Papers ◽

Important Health ◽

High Concern

Background: Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern. Objective: This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber – a commonly used spice - as an anti-obesity agent. Methods: Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants’ regulatory properties in obesity was summarized. Particular attention was paid to curcumin – the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed. Results: Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties. Conclusions: This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

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Protective role of Sterculia tragacantha aqueous extract on pancreatic gene expression and oxidative stress parameters in streptozotocin-induced diabetic rats

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2021-0020 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Basiru Olaitan Ajiboye ◽

Babatunji Emmanuel Oyinloye ◽

Jennifer Chidera Awurum ◽

Sunday Amos Onikanni ◽

Adedotun Adefolalu ◽

...

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Protective Role ◽

Diabetic Rats ◽

Gene Expressions ◽

Ki 67 ◽

Oxidative Stress Parameters ◽

And Oxidative Stress ◽

Stress Parameters

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.

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Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.2.h751 ◽

1994 ◽

Vol 267 (2) ◽

pp. H751-H756 ◽

Cited By ~ 7

Author(s):

A. W. Cowley ◽

E. Szczepanska-Sadowska ◽

K. Stepniakowski ◽

D. Mattson

Keyword(s):

Body Weight ◽

Arginine Vasopressin ◽

Plasma Catecholamines ◽

Plasma Osmolality ◽

Sprague Dawley ◽

Prolonged Administration ◽

Chronic Stimulation ◽

Sustained Hypertension ◽

Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

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Pineal denervation by cervical sympathetic ganglionectomy suppresses the role of photoperiod on pregnancy or pseudopregnancy, body weight and moulting periods in the mink (Mustela vison)

Journal of Endocrinology ◽

10.1677/joe.0.1070031 ◽

1985 ◽

Vol 107 (1) ◽

pp. 31-39 ◽

Cited By ~ 19

Author(s):

L. Martinet ◽

D. Allain ◽

Y. Chabi

Keyword(s):

Body Weight ◽

Environmental Factors ◽

Prolactin Secretion ◽

Corpora Lutea ◽

Progesterone Secretion ◽

Cervical Ganglion ◽

Cervical Sympathetic ◽

Implantation Period ◽

Short Days

ABSTRACT In mink, termination of the delayed implantation period, following reactivation of the corpora lutea, and onset of the spring moult are associated with a rise in prolactin secretion triggered by increasing daylength, while decreasing daylength induces the autumn moult. To establish whether suppression of the function of the pineal rendered the mink unresponsive to daylength changes, the superior cervical ganglion was removed bilaterally 2–4 weeks before mating. Intact and operated females were then left outdoors or were put under a lighting regime of either 15 h light: 9 h darkness (15L: 9D) or 8L: 16D. In July, at the end of the spring moult, the 15L: 9D lighting regime was changed to one of 8L: 16D. Under artificial photoperiods ganglionectomy suppressed the stimulatory role of long days and the inhibitory role of short days on prolactin secretion, and consequently on progesterone secretion and spring moult. Neither was the autumn moult, induced early in intact females by the change to a short photoperiod, advanced in ganglionectomized females, showing that the latter were unresponsive to the artificial modification of the photoperiod. However, in animals kept outdoors, prolactin and progesterone secretion and spring moult were not changed by ganglionectomy. Increase in body weight and autumn moult were only slightly delayed by the operation suggesting that other environmental factors had replaced the synchronizing effect of the daylength changes. Alternatively the desynchronization between intact females responsive to photoperiodism and those rendered unresponsive may be too slow to be observed soon after ganglionectomy. J. Endocr. (1985) 107, 31–39

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