scholarly journals Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jongwan Kim ◽  
Eun-Young Yun ◽  
Fu-Shi Quan ◽  
Seung-Won Park ◽  
Tae-Won Goo
Keyword(s):  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Central Administration ◽  
High Fat ◽  
Signal Transducers ◽  
Diet Induced Obesity ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
The Central Nervous System

Theα-glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).

scholarly journals Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

2017 ◽  
Vol 59 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Long The Nguyen ◽  
Sonia Saad ◽  
Yi Tan ◽  
Carol Pollock ◽  
Hui Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Mrna Level ◽  
Metabolic Stress ◽  
High Fat ◽  
Chemical Chaperone ◽  
Protein Levels

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

scholarly journals Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma
Keyword(s):  
Body Weight ◽  
Body Temperature ◽  
Total Cholesterol ◽  
High Fat Diet ◽  
Moringa Oleifera ◽  
Chronic Administration ◽  
The Body ◽  
Atherogenic Index ◽  
High Fat ◽  
Diet Induced Obesity

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.

High-fat diet leads to elevated lipid accumulation and endoplasmic reticulum stress in oocytes, causing poor embryo development

2020 ◽  
Vol 32 (14) ◽  
pp. 1169
Author(s):  
Arpitha Rao ◽  
Aparna Satheesh ◽  
Guruprasad Nayak ◽  
Pooja Suresh Poojary ◽  
Sandhya Kumari ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
Developmental Potential ◽  
Diet Induced Obesity ◽  
Activating Transcription Factor ◽  
Elevated Lipid

The present study was designed to investigate the effect of diet-induced obesity on endoplasmic reticulum (ER) stress in oocytes. Swiss albino mice (3 weeks old) were fed with a high-fat diet (HFD) for 8 weeks. Oocytes were assessed for lipid droplet accumulation, oxidative stress, ER stress and their developmental potential invitro. High lipid accumulation (P&lt;0.01) and elevated intracellular levels of reactive oxygen species were observed in both germinal vesicle and MII oocytes of HFD-fed mice (P&lt;0.05 and P&lt;0.01 respectively compared with control). Further, expression of the ER stress markers X-box binding protein 1 (XBP1), glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4) and activating transcription factor 6 (ATF6) was significantly (P&lt;0.001) higher in oocytes of the HFD than control group. Oocytes from HFD-fed mice exhibited poor fertilisation and blastocyst rates, a decrease in total cell number and high levels of DNA damage (P&lt;0.01) compared with controls. In conclusion, diet-induced obesity resulted in elevated lipid levels and higher oxidative and ER stress in oocytes, which contributed to the compromised developmental potential of embryos.

scholarly journals Reversal of Diet-Induced Obesity Increases Insulin Transport into Cerebrospinal Fluid and Restores Sensitivity to the Anorexic Action of Central Insulin in Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1047-1054 ◽  
Author(s):  
Denovan P. Begg ◽  
Joram D. Mul ◽  
Min Liu ◽  
Brianne M. Reedy ◽  
David A. D'Alessio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
High Fat Diet ◽  
Male Rats ◽  
Control Group ◽  
Chow Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Insulin Transport ◽  
The Central Nervous System

Abstract Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

scholarly journals Differential Effects of Combined Soluble Epoxide Hydrolase Inhibitor t-TUCB and n-3 Epoxides in Diet-Induced Obesity

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1260-1260
Author(s):  
Yang Yang ◽  
Xinyun Xu ◽  
Christophe Morisseau ◽  
Bruce Hammock ◽  
Ahmed Bettaieb ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Protein Expression ◽  
Cold Tolerance ◽  
High Fat Diet ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Brown Adipose

Abstract Objectives Brown adipose tissue (BAT) is a promising target for obesity prevention. N-3 epoxides are fatty acid epoxides produced from n-3 polyunsaturated fatty acids and shown to be beneficial for health. However, these epoxides are unstable and quickly metabolized by the cytosolic soluble epoxide hydrolase (sEH). Here, we investigated the effects of sEH inhibitor (t-TUCB) alone or combined with two different n-3 epoxides on BAT activation in the development of diet-induced obesity and associated metabolic disorders. Methods Male C57BL6/J mice were fed a high-fat diet and received either of the following treatment: the vehicle control, t-TUCB alone (T), or t-TUCB combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) via osmotic minipump delivery near the interscapular BAT for 6 weeks. Mice were examined for changes in body weight, food intake, glucose, insulin, and cold tolerance tests, and indirect calorimetry. Blood and tissue biochemical analyses were also performed to assess changes in metabolic homeostasis. Results Although no differences in food intake were observed, there were small but significant increases in body weight in both T and T + EDP groups. Mice in the T + EDP and T + EEQ groups showed significant decreases in fasting glucose and serum TG levels, higher core body temperature, and better cold tolerance compared to the controls. However, heat production was significantly increased only in the T + EEQ group. Thermogenic UCP1 protein expression showed a moderate, but not significant, increase in the T + EEQ group. On the other hand, PGC1 α protein expression was significantly increased in the T, T + EDP, and T + EEQ groups compared to the controls. Perilipin protein expression and phosphorylation were also significantly increased in the three treated groups. In contrast, protein expression of FABP4 and HSL was only increased in the T and T + EDP groups, and CD36 protein expression was only increased in the T + EEQ group. Conclusions Our results suggest that sEH pharmacological inhibition by t-TUCB combined with n-3 epoxides may prevent high-fat diet-induced glucose and lipid disorders, in part through increased thermogenesis and upregulating of protein expression of thermogenic and lipid metabolic genes. Funding Sources The work was supported by NIH grants to L.Z., A.B., and B.D.H.

scholarly journals Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity

2019 ◽  
Vol 8 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Anna C Simcocks ◽  
Kayte A Jenkin ◽  
Lannie O’Keefe ◽  
Chrishan S Samuel ◽  
Michael L Mathai ◽  
...  
Keyword(s):  
Body Weight ◽  
G Protein ◽  
High Fat Diet ◽  
Chow Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
G Protein Coupled Receptor ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
G Protein Coupled

Atypical cannabinoid compounds O-1602 and O-1918 are ligands for the putative cannabinoid receptors G protein-coupled receptor 55 and G protein-coupled receptor 18. The role of O-1602 and O-1918 in attenuating obesity and obesity-related pathologies is unknown. Therefore, we aimed to determine the role that either compound had on body weight and body composition, renal and hepatic function in diet-induced obesity. Male Sprague–Dawley rats were fed a high-fat diet (40% digestible energy from lipids) or a standard chow diet for 10 weeks. In a separate cohort, male Sprague–Dawley rats were fed a high-fat diet for 9 weeks and then injected daily with 5 mg/kg O-1602, 1 mg/kg O-1918 or vehicle (0.9% saline/0.75% Tween 80) for a further 6 weeks. Our data demonstrated that high-fat feeding upregulates whole kidney G protein receptor 55 expression. In diet-induced obesity, we also demonstrated O-1602 reduces body weight, body fat and improves albuminuria. Despite this, treatment with O-1602 resulted in gross morphological changes in the liver and kidney. Treatment with O-1918 improved albuminuria, but did not alter body weight or fat composition. In addition, treatment with O-1918 also upregulated circulation of pro-inflammatory cytokines including IL-1α, IL-2, IL-17α, IL-18 and RANTES as well as plasma AST. Thus O-1602 and O-1918 appear not to be suitable treatments for obesity and related comorbidities, due to their effects on organ morphology and pro-inflammatory signaling in obesity.

scholarly journals Evaluation of voglibose on body weight in rats

2019 ◽  
Vol 8 (6) ◽  
pp. 1159
Author(s):  
Sarita Mulkalwar ◽  
Tanya Gupta ◽  
Vishwanath Kulkarni ◽  
A. V. Tilak ◽  
B. T. Rane ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
High Fat Diet ◽  
Normal Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Obesity Drugs

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.

Different Responses to a High-Fat Diet in IL-6 Conditional Knockout Mice Driven by Constitutive GFAP-Cre and Synapsin 1-Cre Expression

2019 ◽  
Vol 109 (2) ◽  
pp. 113-130 ◽  
Author(s):  
Olaya Fernández-Gayol ◽  
Paula Sanchis ◽  
Kevin Aguilar ◽  
Alicia Navarro-Sempere ◽  
Gemma Comes ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Control Diet ◽  
Conditional Knockout ◽  
Mrna Levels ◽  
High Fat ◽  
Significant Difference ◽  
Cellular Source ◽  
The Central Nervous System ◽  
Synapsin 1

Background/Aims: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, at least in part through actions in the central nervous system (CNS) from local sources. Methods: We herewith report results obtained in conditional IL-6 KO mice for brain cells (Il6ΔGfap and Il6ΔSyn). Results: The reporter RiboTag mouse line demonstrated specific astrocytic expression of GFAP-dependent Cre in the hypothalamus but not in other brain areas, whereas that of synapsin 1-dependent Cre was specific for neurons. Feeding a high-fat diet (HFD) or a control diet showed that Il6ΔGfap and Il6ΔSyn mice were more prone and resistant, respectively, to HFD-induced obesity. Energy intake was not altered in HFD experiments, but it was reduced in Il6ΔSyn male mice following a 24-h fast. HFD increased circulating insulin, leptin, and cholesterol levels, decreased triglycerides, and caused impaired responses to the insulin and glucose tolerance tests. In Il6ΔGfap mice, the only significant difference observed was an increase in insulin levels of females, whereas in Il6ΔSyn mice the effects of HFD were decreased. Hypothalamic Agrp expression was significantly decreased by HFD, further decreased in Il6ΔGfap, and increased in Il6ΔSyn female mice. Hypothalamic Il-6 mRNA levels were not decreased in Il6ΔSyn mice and even increased in Il6ΔGfapmale mice. Microarray analysis of hypothalamic RNA showed that female Il6ΔGfap mice had increased interferon-related pathways and affected processes in behavior, modulation of chemical synaptic transmission, learning, and memory. Conclusion: The present results demonstrate that brain production of IL-6 regulates body weight in the context of caloric excess and that the cellular source is critical.

scholarly journals Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization

2016 ◽  
Vol 310 (7) ◽  
pp. R640-R658 ◽  
Author(s):  
James E. Blevins ◽  
Benjamin W. Thompson ◽  
Vishwanath T. Anekonda ◽  
Jacqueline M. Ho ◽  
James L. Graham ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Short Term ◽  
Satiety Response ◽  
Diet Induced Obesity ◽  
Sustained Reduction ◽  
Oxytocin Infusion ◽  
Term Administration ◽  
The Central Nervous System

Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.

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