scholarly journals Effect of treadmill exercise on ER stress and insulin resistance in the hippocampus of high-fat diet fed rats

2015 ◽  
Vol 24 (2) ◽  
pp. 143-151
Author(s):  
Kang Eun Bum
Keyword(s):  
Insulin Resistance ◽  
Er Stress ◽  
High Fat Diet ◽  
Treadmill Exercise ◽  
High Fat

scholarly journals 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

2012 ◽  
Vol 302 (6) ◽  
pp. E654-E665 ◽  
Author(s):  
Banumathi K. Cole ◽  
Norine S. Kuhn ◽  
Shamina M. Green-Mitchell ◽  
Kendall A. Leone ◽  
Rebekah M. Raab ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Stress Markers ◽  
Deficient Mice

Central obesity is associated with chronic inflammation, insulin resistance, β-cell dysfunction, and endoplasmic reticulum (ER) stress. The 12/15-lipoxygenase enzyme (12/15-LO) promotes inflammation and insulin resistance in adipose and peripheral tissues. Given that obesity is associated with ER stress and 12/15-LO is expressed in adipose tissue, we determined whether 12/15-LO could mediate ER stress signals. Addition of 12/15-LO lipid products 12(S)-HETE and 12(S)-HPETE to differentiated 3T3-L1 adipocytes induced expression and activation of ER stress markers, including BiP, XBP-1, p-PERK, and p-IRE1α. The ER stress inducer, tunicamycin, upregulated ER stress markers in adipocytes with concomitant 12/15-LO activation. Addition of a 12/15-LO inhibitor, CDC, to tunicamycin-treated adipocytes attenuated the ER stress response. Furthermore, 12/15-LO-deficient adipocytes exhibited significantly decreased tunicamycin-induced ER stress. 12/15-LO action involves upregulation of interleukin-12 (IL-12) expression. Tunicamycin significantly upregulated IL-12p40 expression in adipocytes, and IL-12 addition increased ER stress gene expression; conversely, LSF, an IL-12 signaling inhibitor, and an IL-12p40-neutralizing antibody attenuated tunicamycin-induced ER stress. Isolated adipocytes and liver from 12/15-LO-deficient mice fed a high-fat diet revealed a decrease in spliced XBP-1 expression compared with wild-type C57BL/6 mice on a high-fat diet. Furthermore, pancreatic islets from 12/15-LO-deficient mice showed reduced high-fat diet-induced ER stress genes compared with wild-type mice. These data suggest that 12/15-LO activity participates in ER stress in adipocytes, pancreatic islets, and liver. Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity.

scholarly journals Exercise Alleviates Cognitive Functions by Enhancing Hippocampal Insulin Signaling and Neuroplasticity in High-Fat Diet-Induced Obesity

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1603 ◽  
Author(s):  
Hye-Sang Park ◽  
Sang-Seo Park ◽  
Chang-Ju Kim ◽  
Mal-Soon Shin ◽  
Tae-Woon Kim
Keyword(s):  
Insulin Resistance ◽  
Cognitive Function ◽  
Physical Exercise ◽  
Dentate Gyrus ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Treadmill Exercise ◽  
High Fat ◽  
Brain Functions ◽  
Impaired Cognitive Function

Obesity, caused by a high-fat diet (HFD), leads to insulin resistance, which is a precursor of diabetes and a risk factor for impaired cognitive function, dementia, and brain diseases, such as Alzheimer’s disease. Physical exercise has positive effects on obesity and brain functions. We investigated whether the decline in cognitive function caused by a HFD could be improved through exercise by examining insulin signaling pathways and neuroplasticity in the hippocampus. Four-week-old C57BL/6 male mice were fed a HFD or a regular diet for 20 weeks, followed by 12 weeks of treadmill exercise. To ascertain the effects of treadmill exercise on impaired cognitive function caused by obesity, the present study implemented behavioral testing (Morris water maze, step-down). Moreover, insulin-signaling and neuroplasticity were measured in the hippocampus and dentate gyrus. Our results demonstrated that HFD-fed obesity-induced insulin resistance was improved by exercise. In addition, the HFD group showed a decrease in insulin signaling and neuroplasticity in the hippocampus and the dentate gyrus and increased cognitive function impairment, which were reversed by physical exercise. Overall, our findings indicate that physical exercise may act as a non-pharmacologic method that protects against cognitive dysfunction caused by obesity by improving hippocampal insulin signaling and neuroplasticity.

scholarly journals Effect of BI-1 on insulin resistance through regulation of CYP2E1

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Geum-Hwa Lee ◽  
Kyoung-Jin Oh ◽  
Hyung-Ryong Kim ◽  
Hye-Sook Han ◽  
Hwa-Young Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Er Stress ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Stable Expression ◽  
Hepatic Insulin Resistance ◽  
Ros Production ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

Abstract Diet-induced obesity is a major contributing factor to the progression of hepatic insulin resistance. Increased free fatty acids in liver enhances endoplasmic reticulum (ER) stress and production of reactive oxygen species (ROS), both are directly responsible for dysregulation of hepatic insulin signaling. BI-1, a recently studied ER stress regulator, was examined to investigate its association with ER stress and ROS in insulin resistance models. To induce obesity and insulin resistance, BI-1 wild type and BI-1 knock-out mice were fed a high-fat diet for 8 weeks. The BI-1 knock-out mice had hyperglycemia, was associated with impaired glucose and insulin tolerance under high-fat diet conditions. Increased activity of NADPH-dependent CYP reductase-associated cytochrome p450 2E1 (CYP2E1) and exacerbation of ER stress in the livers of BI-1 knock-out mice was also observed. Conversely, stable expression of BI-1 in HepG2 hepatocytes was shown to reduce palmitate-induced ER stress and CYP2E1-dependent ROS production, resulting in the preservation of intact insulin signaling. Stable expression of CYP2E1 led to increased ROS production and dysregulation of insulin signaling in hepatic cells, mimicking palmitate-mediated hepatic insulin resistance. We propose that BI-1 protects against obesity-induced hepatic insulin resistance by regulating CYP2E1 activity and ROS production.

scholarly journals Fenofibrate Alleviates Insulin Resistance and Hepatic Steatosis via Modulation of let-7/ SERCA2b Axis

2020 ◽  
Author(s):  
Dan Zhang ◽  
Shan-zhuang Niu ◽  
Yi-cheng Ma ◽  
Bo Zhou ◽  
Yi Deng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Luciferase Reporter ◽  
Control Group ◽  
Chow Diet ◽  
High Fat ◽  
Alcoholic Fatty Liver

Abstract Background: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist, which is widely used in clinical practice to effectively ameliorates the development of NAFLD. However, the molecular mechanism remains largely unknown, the present study aimed to investigate the role and specific mechanism of fenofibrate on lipid metabolism disorders associated diseases.Methods: The male C57BL6/J mice were divided into 3 groups, the mice in control group (n=10) were fed with normal chow diet, and the mice in HFD-fed group (n =10) were fed with a high fat diet (HFD) for 14 weeks. For the fenofibrate +HFD-fed group (n =10), the mice fed HFD were orally gavaged with fenofibrate (40 mg/kg) daily for the last 4 weeks. Body weight and hip width were measured. Macrosteatosis and fat deposition in the liver were measured by H&E staining and Oil red O staining individually. The levels of serum and hepatic triglyceride were measured, and HOMA-IR, HOMA-ISI were analyzed. The levels of SCD-1, Bip, CHOP and SERCA2b were measured by western blotting. The expression of let-7 were analyzed by qPCR, and the complementarity between the 3′-UTR of SERCA2b gene and let-7 was measured by luciferase reporter assay.Results: Fenofibrate reduces hepatic steatosis and insulin resistance in HFD-fed mice. Fnofibrate alleviates endoplasmic reticulum stress (ER stress) of mice fed a high fat diet (HFD). Fenofibrate increases the levels of Sarco-endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) which serves as a regulator of ER stress. Further, the levels of let-7 microRNA is also regulated by fenofibrate, and let-7 directly targets 3’-UTR of SERCA2b. Conclusion: The present data suggests that fenofibrate alleviates ER stress through the let-7/SERCA2b axis to protect against excessive lipid accumulation in the liver of Non-alcoholic fatty liver disease (NAFLD) mice.

scholarly journals Osteocalcin Reverses Endoplasmic Reticulum Stress and Improves Impaired Insulin Sensitivity Secondary to Diet-Induced Obesity Through Nuclear Factor-κB Signaling Pathway

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1055-1068 ◽  
Author(s):  
Bo Zhou ◽  
Huixia Li ◽  
Lin Xu ◽  
Weijin Zang ◽  
Shufang Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Insulin Sensitivity ◽  
Er Stress ◽  
High Fat Diet ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
High Fat ◽  
Impaired Insulin

Abstract Osteocalcin, a synthetic osteoblast-specific protein, has recently emerged as an important regulator of energy metabolism, but the underlying mechanisms are not fully understood. In the present study, mice fed a high-fat diet and receiving osteocalcin showed reduced body weight gain, less fat pad gain, and improved insulin sensitivity as well as increased energy expenditure compared with mice fed a high-fat diet and receiving vehicle. Meanwhile, increased endoplasmic reticulum (ER) stress, defective insulin signaling, and mitochondrial dysfunction induced by obesity were also effectively alleviated by treatment with osteocalcin. Consistent with these findings, the addition of osteocalcin to the culture medium of 3T3-L1 adipocytes, Fao liver cells, and L6 muscle cells markedly reduced ER stress and restored insulin sensitivity. These effects were nullified by blockade of nuclear factor–κB (NF-κB) or phosphatidylinositol 3-kinase but not by U0126, a mitogen-activated protein kinase inhibitor, indicating the causative role of phosphatidylinositol 3-kinase/NF-κB in action of osteocalcin. In addition, the reversal effects of osteocalcin in cells deficient in X-box–binding protein-1, a transcription factor that modulates ER stress response, further confirmed its protective role against ER stress and insulin resistance. Our findings suggest that osteocalcin attenuates ER stress and rescues impaired insulin sensitivity in insulin resistance via the NF-κB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.

scholarly journals The Role of Skeletal Muscle Tribbles 3 (TRB3) on Endoplasmic Reticulum (ER) stress‐ and high fat diet‐induced insulin resistance

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Ho‐Jin Koh ◽  
Taro Toyoda ◽  
Michelle M Jung ◽  
Min‐Young Lee ◽  
Michael F Hirshman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
High Fat Diet ◽  
High Fat

Dapagliflozin not only improves hepatic injury and pancreatic endoplasmic reticulum stress, but also induces hepatic gluconeogenic enzymes expression in obese rats

2019 ◽  
Vol 133 (23) ◽  
pp. 2415-2430 ◽  
Author(s):  
Myat Theingi Swe ◽  
Laongdao Thongnak ◽  
Krit Jaikumkao ◽  
Anchalee Pongchaidecha ◽  
Varanuj Chatsudthipong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Er Stress ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
High Fat Diet ◽  
Plasma Glucose Level ◽  
Hepatic Injury ◽  
High Fat ◽  
Gluconeogenic Enzymes ◽  
Obese Rats

Abstract Background: With an increasing prevalence of obesity and metabolic syndrome, exploring the effects and delineating the mechanisms of possible therapeutic agents are of critical importance. We examined the effects of SGLT2 inhibitor-dapagliflozin on insulin resistance, hepatic gluconeogenesis, hepatic injury and pancreatic ER stress in high-fat diet-induced obese rats. Materials and methods: Male Wistar rats were fed with normal diet (ND) or high-fat diet for 16 weeks. Then high-fat rats were given vehicle (HF) or dapagliflozin (1 mg/kg/day; HFDapa) or metformin (30 mg/kg/day; HFMet) for another 4 weeks. Results: We found that dapagliflozin ameliorated high-fat diet-induced insulin resistance. The fasting plasma glucose level was comparable among groups, although dapagliflozin treatment led to substantial glycosuria. Hepatic gluconeogenic enzymes, PEPCK, G6Pase and FBPase, expression was not different in HF rats compared with ND rats. Meanwhile, dapagliflozin-treated group exhibited the elevation of these enzymes in parallel with the rise of transcription factor CREB, co-factor PGC1α and upstream regulator SIRT1. Hepatic oxidative stress, inflammation and NAFLD activity score as well as hepatic and pancreatic ER stress and apoptosis in obese rats were attenuated by dapagliflozin. Conclusion: We conclude that dapagliflozin improved obesity-related insulin resistance, hepatic and pancreatic injury independent of fasting plasma glucose level. Of note, dapagliflozin-induced glycosuria apparently triggered the up-regulation of hepatic gluconeogenic enzymes to prevent hypoglycemia.

scholarly journals RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance

2021 ◽  
Vol 14 (11) ◽  
pp. 1178
Author(s):  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Er Stress ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Metabolic Stress ◽  
Normal Diet ◽  
High Fat

Inflammation and immunity are linked to the onset and development of obesity and metabolic disorders. Pattern recognition receptors (PRRs) are key regulators of inflammation and immunity in response to infection and stress, and they have critical roles in metainflammation. In this study, we investigated whether RIG-I (retinoic acid-inducible gene I)-like receptors were involved in the regulation of obesity-induced metabolic stress in RIG-I knockout (KO) mice fed a high-fat diet (HFD). RIG-I KO mice fed an HFD for 12 weeks showed greater body weight gain, higher fat composition, lower lean body mass, and higher epididymal white adipose tissue (eWAT) weight than WT mice fed HFD. In contrast, body weight gain, fat, and lean mass compositions, and eWAT weight of MDA5 (melanoma differentiation-associated protein 5) KO mice fed HFD were similar to those of WT mice fed a normal diet. RIG-I KO mice fed HFD exhibited more severely impaired glucose tolerance and higher HOMA-IR values than WT mice fed HFD. IFN-β expression induced by ER stress inducers, tunicamycin and thapsigargin, was abolished in RIG-I-deficient hepatocytes and macrophages, showing that RIG-I is required for ER stress-induced IFN-β expression. Our results show that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, presenting a novel role of RIG-I in the development of obesity and metabolic disorders.

Sign in / Sign up

Export Citation Format

Share Document