Effect of High Fat Diet and Exercise Training on Endoplasmic Reticulum (ER) Stress of Skeletal Muscle in Rat

AbstractIntroductionExercise training is beneficial for reducing obesity. In particular, exercise training can lower the catecholamine concentration in circulation. Renalase, whose expression was first confirmed in the kidneys, is a physiologically active substance that decomposes circulating catecholamines; additionally, it has been reported to be present in the skeletal muscles. The aim of this study was to clarify the expression of renalase in the skeletal muscles and kidneys after high-intensity exercise training in obese mice.Material and methodsThe mice were divided into four groups: normal diet and sedentary, normal diet and exercise training, high-fat diet and sedentary, and high-fat diet and exercise training, and the test was performed for 8 weeks.ResultsBody weight and skeletal muscle wet weight were reduced by high-fat diet intake but were rescued by training. Skeletal muscle renalase gene expression was significantly increased by exercise training. However, in the kidneys the gene expression of renalase was significantly increased by high-fat diet intake and exercise training. No significant changes were observed in the gene expression of catecholamine-degrading enzymes, catechol-O-methyltransferase and monoamine oxidase A and B.ConclusionWe demonstrated that exercise training increased the gene expression of renalase in the skeletal muscles and kidneys, thus lowering circulating catecholamine levels. This may lead to amelioration of obesity as catecholamines are lipolytic.

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

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1154.5 ◽

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

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SUN-LB118 Mice With Skeletal Muscle-Specific DRP1 Deficiency Are Resistant to Obesity and Diabetes Induced by a High Fat Diet

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2320 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Renato Daniel Jensen ◽

Joshua Peterson ◽

Benjamin Allington ◽

Alayna Dieter ◽

Linhai Cheng ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Endoplasmic Reticulum ◽

Energy Expenditure ◽

Er Stress ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Expression Of Genes ◽

Obesity And Diabetes

Abstract The skeletal muscle of type 2 diabetics exhibits mitochondrial dysfunction associated with increased mitochondrial fission. Dynamin-related protein 1 (DRP1) is responsible for mitochondrial division, whereas mitochondrial-endoplasmic reticulum contacts (MERCs) mark mitochondrial sites where fission occurs. Here, we have shown that skeletal muscle-specific DRP1 knock out (KO) mice are partly protected from high fat diet-induced obesity and diabetes, and exhibit increased insulin and glucose tolerance along with lower insulinemia. We also found that KO mice exhibit increased energy expenditure per unit of lean mass. Isolated DRP1-deficient skeletal muscle fibers from KO mice fed high fat diet have reduced respiratory capacity when exposed to ADP and palmitoyl-carnitine, but not when exposed to ADP, pyruvate, and malate. Additionally, the skeletal muscle of KO mice fed normal chow exhibited altered expression of genes associated with MERCs and increased expression of genes linked to ER stress. We observed substantial increases in gene expression of FGF21, a downstream signal of the ER stress response, in KO mice. However, FGF21 plasma concentration in KO mice was not elevated. Additionally, changes in MERC gene expression could potentially alter calcium signaling between the mitochondria and endoplasmic reticulum, changing insulin sensitivity in KO mice. In conclusion, we have shown that skeletal muscle-specific DRP1 KO mice are resistant to high fat diet-induced obesity and diabetes, perhaps due to elevated energy expenditure and differential mitochondrial respiratory adaptations to different substrates. Although FGF21 does not appear to contribute to this effect, it is possible that other ER-stress signals might help explain the observed phenotype in KO mice.

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

Journal of Molecular Endocrinology ◽

10.1530/jme-17-0056 ◽

2017 ◽

Vol 59 (1) ◽

pp. 81-92 ◽

Cited By ~ 7

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.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00373.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. E654-E665 ◽

Cited By ~ 35

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.

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