scholarly journals Elaiophylin reduces body weight and lowers glucose levels in obese mice by activating AMPK

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruoxuan Bao ◽  
Yongmei Meng ◽  
Haibo Zhang ◽  
Chen Yang ◽  
Wei Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Chronic Diseases ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Pharmacological Intervention ◽  
Obese Mouse ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Treatment Of Obesity

AbstractObesity is an epidemic affecting 13% of the global population and increasing the risk of many chronic diseases. However, only several drugs are licensed for pharmacological intervention for the treatment of obesity. As a master regulator of metabolism, the therapeutic potential of AMPK is widely recognized and aggressively pursued for the treatment of metabolic diseases. We found that elaiophylin (Ela) rapidly activates AMPK in a panel of cancer-cell lines, as well as primary hepatocytes and adipocytes. Meanwhile, Ela inhibits the mTORC1 complex, turning on catabolism and turning off anabolism together with AMPK. In vitro and in vivo studies showed that Ela does not activate AMPK directly, instead, it increases cellular AMP/ATP and ADP/ATP ratios, leading to AMPK phosphorylation in a LKB1-dependent manner. AMPK activation induced by Ela caused changes in diverse metabolic genes, thereby promoting glucose consumption and fatty acid oxidation. Importantly, Ela activates AMPK in mouse liver and adipose tissue. As a consequence, it reduces body weight and blood glucose levels and improves glucose and insulin tolerance in both ob/ob and high-fat diet-induced obese mouse models. Our study has identified a novel AMPK activator as a candidate drug for the treatment of obesity and its associated chronic diseases.

scholarly journals PHARMACOLOGICAL SCREENING OF ANTI-OBESITY POTENTIAL OF ACORUS CALAMUS LINN. IN HIGH FAT CAFETERIA DIET FED OBESE RATS

2017 ◽  
Vol 10 (4) ◽  
pp. 384 ◽  
Author(s):  
Athesh K ◽  
Joshi G
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
Acorus Calamus ◽  
Dependent Manner ◽  
Fat Pad ◽  
High Fat ◽  
Dose Levels ◽  
Dose Dependent

Objective: To study the anti-obesity potential of aqueous rhizome extract of Acoruscalamus Linn. (AREAC)in high fat diet fed obese rats.Methods: Adult strain male Wistar rats used in this study were fed with High Fat Diet (HFD) for 60 days. For the treatment groups,AREAC was administered in a dose levels of100, 200 and 300 mg/kgbw, orally once a day along with HFD. Rats fed with normal pellet chow were served as normal control. The effect of AREAC on physical parameterssuch as body weight, organ weight, fat pad weights and various biochemical parameterslike serum glucose, insulin, leptin,lipid profile, liver markers, kidney markers and oxidative stress markers were analysed.In-vitro pancreatic lipase inhibition assay of AREAC was also studied.Results: Data of in-vivo studies revealedsignificant (p<0.05) reduction in percentage body weight gain, organ weights, fat pad weights and levels of serum glucose, insulin and leptin after treatment with AREAC in a dose dependent manner. Also, administration of AREAC significantly inhibited the increases in the concentrations of triglycerides, total cholesterol, LDL-cholesterol, VLDL-cholesterol, free-fatty acid and phospholipids in a dose dependent manner whereas, the level of HDL-cholesterol was found to be elevated on treatment. Moreover, on treatment with test drug,the elevated levels of serum liver and kidney markerssuch as AST, ALT, ALP, urea, creatinine were also brought back to near normalcy. Antioxidant status was found to be enhanced in liver tissues after treatment.In-vitro studies showed significant inhibition in the activity of pancreatic lipaseby AREAC.Conclusion: The data of the results obtained clearly depicted that AREAC was found to have pronounced anti-obesity activity particularly at the dose levels of 300 mg/kg bw.Key Words: Obesity, High Fat Diet, Leptin, AcoruscalamusLinn., Orlistat.  

scholarly journals Betulinic acid inhibits glioma cell viability by downregulation of NF-κB and enhancement of apoptosis

2021 ◽  
Vol 19 (12) ◽  
pp. 2545-2551
Author(s):  
Zhu Yaozu ◽  
Yang Liu ◽  
Huang Zhao ◽  
Peng Peng ◽  
Zhang Tingbao ◽  
...  
Keyword(s):  
Betulinic Acid ◽  
Therapeutic Potential ◽  
Annexin V ◽  
In Vivo Studies ◽  
Proliferative Potential ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Diphenyltetrazolium Bromide ◽  
Inhibitory Potential

Purpose: To determine the inhibitory potential of betulinic acid on pro-survival signaling pathway in glioblastoma.Methods: Changes in viabilities of glioma cells and primary astrocytes were measured using 3-(4, 5dimethylthiazol-2-yl)-2,  5-diphenyltetrazolium bromide (MTT) assay. Apoptotic changes were analyzed using Hoechst 33342 staining and Annexin V-FITC/PI kits. Western blotting was used for assaying the protein expressions of various pro-apoptotic and anti-apoptotic factors.Results: The proliferative potential of U87MG and A172 cells were significantly reduced on treatment with betulinic acid in a concentration- and time-dependent manner. Treatment with betulinic acid at a dose of 8.75 µg/mL increased apoptosis in U87MG and A172 cells to 41.8 ± 0.5 and 48.8 ± 0.5%, respectively (p < 0.05). Betulinic acid significantly decreased intracellular levels of NFκB p65 andsuppressed levels of survivin, XIAP and Bcl-2 in U87MG and A172 cells (p < 0.05). However, betulinic acid significantly increased the levels of Bax and activated caspase-9 and caspase-3 in U87MG and A172 cells (p < 0.05).Conclusion: Betulinic acid inhibited the proliferation of U87MG and A172 glioblastoma cells and mediated their apoptosis. There is need for in vivo studies for validation of the therapeutic potential of betulinic acid as an anti-glioblastoma drug. Keywords: Glioblastoma, Betulinic acid, Proliferation, Apoptosis, Chemotherapy, Intracranial malignancy

scholarly journals Erythropoietin treatment leads to reduced blood glucose levels and body mass: insights from murine models

2010 ◽  
Vol 205 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Odelia Katz ◽  
Matthew Stuible ◽  
Nathalia Golishevski ◽  
Lilach Lifshitz ◽  
Michel L Tremblay ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Murine Models ◽  
Erythroid Precursor ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Diabetes And Obesity

Erythropoietin (EPO) regulates proliferation and differentiation of erythroid precursor cells into erythrocytes. The last decade has revealed non-renal sites of EPO production and extrahematopoietic expression of the EPO receptor, thus suggesting that EPO has pleiotropic functions. Here, we addressed the interplay between EPO/glucose metabolism/body weight by employing a panel of relevant experimental murine models. The models focused on situations of increased EPO levels, including EPO-injected C57BL/6 and BALB/c mice, as well as transgenic mice (tg6) constitutively overexpressing human EPO, thus exposed to constantly high EPO serum levels. As experimental models for diabetes and obesity, we employed protein Tyr phosphatase 1B (PTP1B) knockout mice associated with resistance to diabetes (PTP1B−/−), and ob/ob mice susceptible to diabetes and obesity. The data presented herein demonstrate EPO-mediated decrease in blood glucose levels in all mice models tested. Moreover, in the ob/ob mice, we observed EPO-mediated attenuation of body weight gain and reduction of hemoglobin A1c. Taken together, our data bear significant clinical implications of EPO treatment in the management of a wide range of metabolic diseases, thus adding an important novel therapeutic potential to this pleiotropic hormone.

scholarly journals Metabolaid® Combination of Lemon Verbena and Hibiscus Flower Extract Prevents High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1204 ◽  
Author(s):  
Young-Sil Lee ◽  
Won-Kyung Yang ◽  
Hwa Kim ◽  
Bokkee Min ◽  
Nuria Caturla ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Synergistic Effects ◽  
Liver Weight ◽  
Acid Oxidation ◽  
High Fat ◽  
Related Factors ◽  
Lippia Citriodora ◽  
Glucose Levels ◽  
Treatment Of Obesity ◽  
Lemon Verbena

Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in traditional medicine formulations to treat asthma and diabetes in South America and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in traditional Chinese medicine in the form of a tea to treat hypertension and inflammation. In the present study, we examined the synergistic effects of a formula of Metabolaid® (MetA), a combination of lemon verbena and hibiscus-flower extracts, on obesity and its complications in high-fat-diet (HFD)-induced obese mice. The results showed that MetA decreased body weight, white adipose tissue (WAT), and liver weight. Additionally, serum and hepatic lipid profiles, glucose levels, glucose tolerance, and cold-induced thermogenesis were significantly improved. Appetite-regulating hormones adiponectin and leptin were significantly increased and decreased, respectively, while the inflammatory-related factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated by MetA. Adipogenesis-activating gene expression was decreased, while increased thermogenesis-inducing genes were upregulated in the WAT, correlating with increased phosphorylation of AMPK and fatty-acid oxidation in the liver. Taken together, these results suggest that MetA decreased obesity and its complications in HFD mice. Therefore, this formula may be a candidate for the prevention and treatment of obesity and its complications.

scholarly journals Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 855 ◽  
Author(s):  
Thomas Murphy ◽  
Bernard Le Foll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Obese Subjects ◽  
Treatment Of Obesity ◽  
Psychiatric Side Effects ◽  
Preclinical And Clinical Studies ◽  
The Impact

Obesity rates are increasing worldwide and there is a need for novel therapeutic treatment options. The endocannabinoid system has been linked to homeostatic processes, including metabolism, food intake, and the regulation of body weight. Rimonabant, an inverse agonist for the cannabinoid CB1 receptor, was effective at producing weight loss in obese subjects. However, due to adverse psychiatric side effects, rimonabant was removed from the market. More recently, we reported an inverse relationship between cannabis use and BMI, which has now been duplicated by several groups. As those results may appear contradictory, we review here preclinical and clinical studies that have studied the impact on body weight of various cannabinoid CB1 drugs. Notably, we will review the impact of CB1 inverse agonists, agonists, partial agonists, and neutral antagonists. Those findings clearly point out the cannabinoid CB1 as a potential effective target for the treatment of obesity. Recent preclinical studies suggest that ligands targeting the CB1 may retain the therapeutic potential of rimonabant without the negative side effect profile. Such approaches should be tested in clinical trials for validation.

scholarly journals Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα

2017 ◽  
Vol 162 (1) ◽  
pp. 212-224 ◽  
Author(s):  
Elizabeth A Krumm ◽  
Vipa J Patel ◽  
Taylor S Tillery ◽  
Ali Yasrebi ◽  
Jianliang Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Dependent Manner ◽  
Hormone Levels ◽  
Glucose Levels ◽  
Insulin Tolerance ◽  
Plasma Hormone ◽  
Liver Gene

Abstract Flame retardants (FRs) such as polybrominated diphenyl ethers and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ERs). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ERα KO mice. Intact WT and KO males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2.5 μg/kg), 2,2’, 4,4-tetrabromodiphenyl ether (BDE-47, 1 or 10 mg/kg), or an OPFR mixture {1 or 10 mg/kg of tris(1, 3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate each} for 28 days. Body weight, food intake, body composition, glucose and insulin tolerance, plasma hormone levels, and hypothalamic and liver gene expression were measured. Expression of neuropeptides, receptors, and cation channels was differentially altered between WT males and females. OPFR suppressed body weight and energy intake in males. FR increased fasting glucose levels in males, and BDE-47 augmented glucose clearance in females. Liver gene expression indicated FXR activation by BDE-47 and PXR and CAR activation by OPFR. In males, OPFR increased ghrelin but decreased leptin and insulin independent of body weight. The loss of ERα reduced the effects of both FR on hypothalamic and liver gene expression and plasma hormone levels. The physiological implications are that males are more sensitive than ovariectomized females to OPFR exposure and that these effects are mediated, in part, by ERα.

scholarly journals Hibiscus noldea (Malvaceae) Aqueous Extract Prevents Insulin Resistance and Protects Pancreatic Islets From Dexamethasone Damages in Rat.

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Ngueguim Tsofack Florence ◽  
Djientcheu Tientcheu Jean Philippe ◽  
Donfack Jean Hubert ◽  
Gounoue Kamkumo Raceline ◽  
Dzeufiet Djomeni Paul Desire ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Blood Glucose ◽  
Lipid Profile ◽  
Pancreatic Islets ◽  
Aqueous Extract ◽  
Hepatic Glycogen ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Blood Glucose Levels

<p><em>Hibiscus noldea</em> leaves-stems aqueous extract is used in Cameroonian traditional medecine to manage diabetes. To investigate the preventive effect of <em>Hibiscus noldea</em> aqueous extract on dexamethasone-induced insulin resistance, the animals received one of the following treatments: distilled water (10 mL/kg), metformine (200 mg/kg), or <em>H. noldea</em> (100 or 200 mg/kg) concomitantly with dexamethasone (0.5 mg/kg, ip) for ten days. Body weight was evaluated daily and blood glucose levels were measured. At the end of experiment, insulin sensitivity test was performed and lipid profile, transaminases Aspartate amino transferase, Alanin amino transferase, malondialdehyde, superoxide dismutase, catalase, and reduced glutathione were evaluated. Histological analysis of the liver was investigated to estimate glycogen content using Periodic Acid Schiff coloration and histomorphometry of pancreatic islets area was performed.</p><p>The administration of dexamethasone during ten days induced body weight loss, hyperglycaemia, insulinresistance, an imbalance in lipid profile, an increase in transaminases and oxidative stress. Dexamethasone treatment also induced an increase in the pancreatic islets area and depletion in the levels of hepatic glycogen. Concomitant administration of dexamethasone and the aqueous plant extract prevented the rise in blood glucose levels, reduced insulinresistance, improved lipid profile and oxidative status. The aqueous extract of <em>H. noldea</em> prevented the use of glycogen storage and the increase in pancreatic islet area in dose dependent manner.</p><p>Conclusion: The stem leaves aqueous extract from <em>Hibiscus noldea</em> have the ability to reduce insulinresistance via its antihyperglycaemic, hypolipidemic and antioxidant activities. These results justify the use of this extract in the management of diabetic state.</p>

scholarly journals Toxicological implications of Margaritaria discoidea aqueous seed extract on Na+, K+-ATPase specific activity, glucose and serum electrolytes level in wistar rats

2016 ◽  
Vol 4 (2) ◽  
pp. 210
Author(s):  
Chimaraoke Onyeabo ◽  
Polycarp Nnacheta
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Specific Activity ◽  
Lethal Dose ◽  
Seed Extract ◽  
Albino Rats ◽  
Dependent Manner ◽  
Sodium Potassium ◽  
Glucose Levels ◽  
Dose Dependent

The effect of aqueous seed extract of Margaritaria discoidea on Na+ K+ ATPase activity and toxicity studies of its seed extract were investigated in albino rats. The study involved oral administration of different doses of the aqueous extract to groups of male albino rats at 25, 50,100, and 200mg/kg body weight resulted in significant (p<0.05) decrease in sodium, potassium and glucose levels while chloride and calcium ions showed a significant (p<0.05) increase relative to control. The seed extract also showed significant (p<0.05) decrease in Na+ K+ ATPase specific activity in a dose dependent manner relative to control. The median lethal dose (LD50) of this extract in mice was established at 316.2mg/kg body weight using probit of mortality. The results showed that the acute toxicity potency of the aqueous extract of the seeds was practically non-toxic. The study showed that seeds of Margaritaria discoidea could be toxic if not consumed in moderate quantities.

scholarly journals Role of Medium- and Short-Chain L-3-Hydroxyacyl-CoA Dehydrogenase in the Regulation of Body Weight and Thermogenesis

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4641-4651 ◽  
Author(s):  
Nadja Schulz ◽  
Heinz Himmelbauer ◽  
Michaela Rath ◽  
Michel van Weeghel ◽  
Sander Houten ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Body Temperature ◽  
Knockout Mice ◽  
Fuel Efficiency ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Obese Mouse ◽  
Acid Oxidation ◽  
Trait Locus

Dysregulation of fatty acid oxidation plays a pivotal role in the pathophysiology of obesity and insulin resistance. Medium- and short-chain-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (SCHAD) (gene name, hadh) catalyze the third reaction of the mitochondrial β-oxidation cascade, the oxidation of 3-hydroxyacyl-CoA to 3-ketoacyl-CoA, for medium- and short-chain fatty acids. We identified hadh as a putative obesity gene by comparison of two genome-wide scans, a quantitative trait locus analysis previously performed in the polygenic obese New Zealand obese mouse and an earlier described small interfering RNA-mediated mutagenesis in Caenorhabditis elegans. In the present study, we show that mice lacking SCHAD (hadh−/−) displayed a lower body weight and a reduced fat mass in comparison with hadh+/+ mice under high-fat diet conditions, presumably due to an impaired fuel efficiency, the loss of acylcarnitines via the urine, and increased body temperature. Food intake, total energy expenditure, and locomotor activity were not altered in knockout mice. Hadh−/− mice exhibited normal fat tolerance at 20 C. However, during cold exposure, knockout mice were unable to clear triglycerides from the plasma and to maintain their normal body temperature, indicating that SCHAD plays an important role in adaptive thermogenesis. Blood glucose concentrations in the fasted and postprandial state were significantly lower in hadh−/− mice, whereas insulin levels were elevated. Accordingly, insulin secretion in response to glucose and glucose plus palmitate was elevated in isolated islets of knockout mice. Therefore, our data indicate that SCHAD is involved in thermogenesis, in the maintenance of body weight, and in the regulation of nutrient-stimulated insulin secretion.

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