Methylnaltrexone potentiates body weight and fat reduction with leptin

2018 ◽  
Vol 5 (6) ◽  
pp. 373-378 ◽  
Author(s):  
Chun-Su Yuan, MD, PhD ◽  
Shi Sun, PhD ◽  
Anoja Attele, MD ◽  
Chong-Zhi Wang, PhD ◽  
Robin Tong, BS ◽  
...  
Keyword(s):  
Body Weight ◽  
Neonatal Rat ◽  
Opioid Antagonist ◽  
Fat Pad ◽  
Reduced Body ◽  
Fat Reduction ◽  
Brown Adipose ◽  
The Right ◽  
Neonatal Rat Model ◽  
Daily Intraperitoneal Injection

Objective: Leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. In a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. As opioids increase feeding, opioid antagonists may decrease food intake and body weight. However, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. In this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats.Results: Compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p 0.01). Naloxone or methylnaltrexone significantly potentiated leptin’s effect on body weight (p 0.05 or p 0.01, respectively). After coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p 0.05 or p 0.01, respectively).Conclusions: The data suggest the existence of a peripheral opioid-related mechanism in leptinactive modulation of body weight.

scholarly journals Patchouli Alcohol from Pogostemon Cablin Prevents Development of Obesity and Improves Glucose Tolerance in High Fat Diet-induced Obese Mice (P06-107-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jihye Lee ◽  
Seong-Ho Lee
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Oral Glucose ◽  
Male Mice ◽  
Fat Pad ◽  
High Fat ◽  
Patchouli Alcohol ◽  
Brown Adipose ◽  
Pogostemon Cablin

Abstract Objectives Patchouli alcohol is a sesquiterpene alcohol found in Pogostemon cablin. Recently, we observed that patchouli alcohol reduced lipid accumulation in differentiated 3T3-L1 adipocytes and increased glucose uptake in differentiated C2C12 myocytes. This study was designed to investigate anti-obese and anti-diabetic activities of patchouli alcohol using high fat diet-induced obese mouse model. Methods Forty-eight 5-week old C57BL/6 J male mice were assigned into four groups and fed with 1) normal diet (control), 2) high fat diet, 3) high fat diet with gavaging 25 mg of patchouli alcohol/kg body weight and 4) high fat diet with gavaging 50 mg of patchouli alcohol/kg body weight. High fat diet or control diets were provided to each treatment group for four weeks and then different doses of patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered for following 8 weeks with the diet. At age of week 17, all animals were sacrificed, fat tissues were collected, and tissue weight was measured. In addition, twenty C57BL/6 J male mice were assigned into the same treatment groups above. At the end of the 8 weeks (age of week 17), the mice were fasted for 12 h and the oral glucose tolerance test was performed after intraperitoneal injection of 2 g of anhydrous glucose/kg body weight. The blood was collected from tail at 0, 15, 30, 90 and 120 min after injection and blood glucose level was analyzed using glucose meter. Results Treatment of patchouli alcohol (50 mg/kg body weight) significantly reduced body weight and accumulation of body fat pads which was highly induced by feeding of high fat diet. An analysis of individual fat pad weights (expressed as mg weight of fat pad/g body weight) revealed a significant decrease of epididymal and retroperitoneal fat pad in patchouli alcohol-treated mice whereas brown adipose tissue were not significantly altered. And, slightly improved glucose tolerance was observed at 90 and 120 minutes after glucose injection in mice treated with patchouli alcohol (50 mg/kg body weight) compared to those fed with high fat diet alone. Conclusions We propose a potential use of patchouli alcohol as an anti-obesity compound in obese population. Funding Sources NIFA Hatch grant. Supporting Tables, Images and/or Graphs

scholarly journals Energy homeostasis in apolipoprotein AIV and cholecystokinin-deficient mice

2017 ◽  
Vol 313 (5) ◽  
pp. R535-R548 ◽  
Author(s):  
Jonathan Weng ◽  
Danwen Lou ◽  
Stephen C. Benoit ◽  
Natalie Coschigano ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Fat Mass ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Lipid Transport ◽  
Fat Absorption ◽  
High Fat ◽  
Reduced Body ◽  
Brown Adipose

Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.

scholarly journals Establishment of a hypoxia ischemia reperfusion brain damage model in neonatal rats

2022 ◽  
Author(s):  
xiaoqin fu ◽  
tianlei zhang ◽  
wei lin ◽  
mengdie jiao ◽  
zhiwei zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Brain Tissue ◽  
Brain Damage ◽  
Rat Model ◽  
Ischemia Reperfusion ◽  
Neonatal Rat ◽  
Bridge Method ◽  
Hypoxia Ischemia ◽  
Group A ◽  
Neonatal Rat Model

Objective: Rice-Vannucci model has been widely used as HIE（Hypoxic ischemic encephalopathy ） animal model in the past forty years, but it does not mimic reperfusion injury that occurs during HIE. The aim of the present study was to establish a new neonatal rat model by simulating hypoxia ischemia reperfusion brain damage (HIRBD) through "common carotid artery (CCA) muscle bridge". Methods: Sixty 7-day-old male Sprague-Dawley rats were randomly assigned to group A (HIRBD groups, n=36), group B (Rice-Vannucci group, n=12), and group C (sham-operated group, n=12). Rats in group A were assigned to 3 subgroups (A1-A3, 12 animals/subgroup). Dynamic changes in cerebral blood flow (CBF) were evaluated by the laser speckle imaging system. The status of the CCA was observed under a stereomicroscope. Changes in body weight, gross morphology as well as pathological sections of brain tissue were examined to evaluate the feasibility of the model. Results: The results indicated that CCA muscle bridge successfully blocked the CBF. CBF was restored after removal of the CCA muscle bridge in HIRBD groups. The CCA was in good condition after removing the muscle bridge, and blood supply was not affected. Changes in body weight, gross morphology and pathological sections of brain tissue indicated that ischemia reperfusion induced by the CCA muscle bridge method caused varying degrees of brain damage. Conclusion: CCA muscle bridge method is effective for establishing a reliable, stable, and reproducible neonatal rat model for study of HIRBD.

scholarly journals Inhibition of Sam68 triggers adipose tissue browning

2015 ◽  
Vol 225 (3) ◽  
pp. 181-189 ◽  
Author(s):  
Junlan Zhou ◽  
Min Cheng ◽  
Chan Boriboun ◽  
Mariam M Ardehali ◽  
Changfei Jiang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Acid Oxidation ◽  
M2 Macrophage ◽  
Fat Depots ◽  
Reduced Body ◽  
Brown Adipose ◽  
The Difference

Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders.

scholarly journals Chronic Hindbrain Administration of Oxytocin Elicits Weight Loss in Male Diet-Induced Obese Mice

2021 ◽  
Author(s):  
Melise Marie Edwards ◽  
Ha Khanh Nguyen ◽  
Adam Jay Herbertson ◽  
Andrew Dale Dodson ◽  
Tomasz Wietecha ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Intake ◽  
Uncoupling Protein ◽  
Post Injection ◽  
Reduced Body ◽  
Brown Adipose ◽  
Pre Treatment

Previous studies indicate that oxytocin (OT) administration reduces body weight in high fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake and body composition. OT reduced body weight by approximately 4.5±1.4% in DIO mice relative to OT pre-treatment body weight (P<0.05). These effects were associated with reduced adiposity and adipocyte size (inguinal white adipose tissue (IWAT)] (P<0.05) and attributed, in part, to reduced energy intake (P<0.05) at a dose that did not increase kaolin intake (P=NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05<P<0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature (TIBAT). 4V OT (1 μg) elevated TIBAT at 0.75 (P=0.08), 1, and 1.25 h (P<0.05) post-injection; a higher dose (5 μg) elevated TIBAT at 0.75, 1, 1.25, 1.5, 1.75 (P<0.05), and 2-h (0.05<P<0.1) post-injection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.

Expression enhancement in brown adipose tissue of genes related to thermogenesis and mitochondrial dynamics after administration of pepsin egg white hydrolysate

2018 ◽  
Vol 9 (12) ◽  
pp. 6599-6607 ◽  
Author(s):  
S. Moreno-Fernández ◽  
M. Garcés-Rimón ◽  
J. A. Uranga ◽  
J. Astier ◽  
J. F. Landrier ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Dynamics ◽  
Egg White ◽  
Reduced Body ◽  
Brown Adipose

Pepsin egg white hydrolysate enhanced mitochondria proliferation on brown adipose tissue and thermogenesis. Reduced body weight and adiposity were observed.

Efficacy of exogenous recombinant murine leptin in lean and obese 10- to 12-mo-old female CD-1 mice

1998 ◽  
Vol 275 (4) ◽  
pp. R950-R959 ◽  
Author(s):  
Mary Ann Pelleymounter ◽  
Mary Jane Cullen ◽  
Denis Healy ◽  
Randy Hecht ◽  
Dwight Winters ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Obese Mice ◽  
Appetite Suppression ◽  
Specific Effects ◽  
Leptin Sensitivity ◽  
Fat Reduction ◽  
Body Weights ◽  
High Doses ◽  
The Right

Leptin efficacy was compared in obese and lean female CD-1 mice. Body weights in these 10- to 12-mo-old mice ranged from 29.7 to 62.0 g, and leptin levels correlated with body weight. Mice from the lean and obese ends of the weight distribution were treated with daily peripheral leptin injections (1–100 mg/kg) for a 33-day period. The half-maximal effective doses for weight loss and fat reduction were shifted 0.5–0.7 log to the right for obese mice. Leptin was less efficacious at low doses (1–3 mg/kg) in obese mice but equal to or more efficacious in obese than lean mice at high doses (30–100 mg/kg). Leptin’s initial effects on weight loss could be explained by appetite suppression in both groups, but its effects on fat reduction were greater in leptin-treated than pair-fed mice, particularly in the lean group. Leptin also prevented the elevations in serum corticosterone and ketones found in pair-fed lean mice. These data allow a quantitative comparison of leptin sensitivity in obese vs. lean CD-1 mice and suggest that in mice where obesity is a function of outbreeding and age, leptin sensitivity is moderately reduced. Furthermore, although appetite suppression has a clear role in leptin’s effects on body weight, leptin may also have specific effects on lipid metabolism and mobilization that are different from the metabolic compensations that normally occur with food deprivation.

scholarly journals Acetazolamide and SGLT2 inhibitor as potent drugs for a patient with diabetes mellitus and worsening chronic lymphedema: A case report

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hajime Kataoka
Keyword(s):  
Body Weight ◽  
Fluid Collection ◽  
Sglt2 Inhibitor ◽  
Chloride Concentration ◽  
Tissue Fluid ◽  
Fat Deposits ◽  
Serum Chloride ◽  
The Right ◽  
Chronic Lymphedema

Treatment of lymphedema using a pharmacologic approach is reported to have limited efficacy. Here, I report a patient with type 2 diabetes (T2DM) and acute worsening of her chronic lymphedema, in whom treatment with acetazolamide and a sodiumglucose cotransporter-2 inhibitor (SGLT2i) effectively improved the lymphedema. A 94-year-old woman, who was treated for T2DM, hyperlipidemia, and hypertension for 17 years at my hospital presented to the emergency room because of acute worsening of her chronic right leg lymphedema with increased swelling, tightness, and dull aching. A pharmacologic approach was used to treat her worsening lymphedema. Acetazolamide 500 mg/d was administered to treat the acute tissue fluid collection in the right lymphedematous leg. Ten days later, the patient’s body weight was markedly reduced by 3.2 kg, pitting in the right leg was markedly improved, and the circumference of right limb was decreased. On day 11, the glucose-lowering agent vildagliptin was switched to the SGLT2i empagliflozin 10 mg/d. On day 70, her body weight had decreased further by 2.8 kg, and the circumference of her right limb was greatly reduced compared with that under treatment with acetazolamide. Her serum chloride concentration was increased after treatment, but her hemoglobin and hematocrit values did not change during the study period. In conclusion, acetazolamide and an SGLT2i have acute diuretic effects for draining the excess tissue fluid in the lymphedematous limb without vascular contraction by enhancing vascular tonicity. Additionally, an SGLT2i may have chronic effects for reducing fat deposits in the lymphedematous limb.

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