Chronic everolimus treatment of high‐fat diet mice leads to a reduction in obesity but impaired glucose tolerance

Chang, Geng-Ruei; Hou, Po-Hsun; Wang, Chao-Ming; Wu, Ching-Feng; Su, Huang-Kai; Liao, Huei-Jyuan; Chen, To-Pang

doi:10.1002/prp2.732

Cited by 9 publications

(3 citation statements)

References 57 publications

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“…The exposure of diets extended for 12 weeks and were administered during adulthood. This dietary duration is consistent with other studies examining impacts of long-term high-fat and/or chronic sucrose interventions on rodent physiology ( Aoi et al, 2011 ; Chang et al, 2021 ; Odom et al, 2021 ). It was interesting, although not altogether unexpected, that the HS diet did not cause significant weight gain.…”

Section: Discussionsupporting

confidence: 90%

The Effect of Dietary Fat and Sucrose on Cognitive Functioning in Mice Lacking Insulin Signaling in Neuropeptide Y Neurons

Goodman

Tedesco

et al. 2022

Front. Physiol.

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Obesogenic diets can produce hippocampal insulin resistance and impairments to hippocampal-dependent cognition. This study investigated the effect of disrupted insulin signaling in Neuropeptide Y (NPY) neurons on diet-induced deficits in hippocampal-dependent memory. Wild-type mice and mice that had a targeted knockout of insulin receptors on NPY cells (IRlox/lox;NPYCre/+) were given ad libitum access to a high-fat diet (high fat; HF), 10% sucrose solution (high sugar; HS), both high-fat diet and sucrose solution (high fat, high sugar; HFHS), or a normal fat control chow for 12 weeks. Mice were tested in the Morris Water Maze (MWM), a hippocampal-dependent spatial memory task. Glucose homeostasis was assessed via a glucose tolerance test. Independent of genotype, consumption of HF, but not HS, diet increased energy intake, body weight, and plasma leptin, and impaired glucose tolerance. Disrupted insulin signaling in NPY cells and dietary interventions did not significantly affect the ability of mice to learn the location of the platform in the MWM. However, for IRlox/lox control mice, consumption of HF, but not HS, diet resulted in reduced time spent in the target quadrant during the probe trial, suggesting a hippocampal-dependent memory deficit. IRlox/lox;NPYCre/+ mice had poor performance in the probe trial regardless of diet, suggesting a floor effect. This study did not find adverse effects of chronic sucrose intake on metabolic outcomes or hippocampal-dependent memory. These data also suggest that the effects of HF diet on hippocampal-dependent memory may be dependent on insulin signaling in hippocampal NPY cells.

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Section: Discussionsupporting

confidence: 90%

The Effect of Dietary Fat and Sucrose on Cognitive Functioning in Mice Lacking Insulin Signaling in Neuropeptide Y Neurons

Goodman

Tedesco

et al. 2022

Front. Physiol.

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“…Of note is the comparison between the CMG and CEG schemes, which showed more numerous and more prominent VDs in the hepatocytes of rats exposed to the protocol including EVE, which is an mTOR inhibitor. Regarding other pathological alterations, according to Chang et al [52], EVE usage in mice resulted in decreased weight of the liver with a lowered accumulation of fat. There is data indicating that mTOR inhibitors increase the mortality of a fetus in animals.…”

Section: Discussionmentioning

confidence: 98%

Prenatal Exposition to Different Immunosuppressive Protocols Results in Vacuolar Degeneration of Hepatocytes

Wilk

Szypulska-Koziarska

Oszutowska–Mazurek

et al. 2023

Biology

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Immunosuppressive drugs are essential for transplant recipients, since they prolong proper function of graft; however, they affect the morphology and function of organs, including liver. One commonly observed alteration in hepatocytes is vacuolar degeneration. Numerous medications are contraindicated in pregnancy and breastfeeding, mostly due to a lack of data concerning their advert effects. The aim of the current study was to compare the effects of prenatal exposition to different protocols of immunosuppressants on vacuolar degeneration in the hepatocytes of livers of rats. Thirty-two livers of rats with usage of digital analysis of the images were examined. Area, perimeter, axis length, eccentricity and circularity regarding vacuolar degeneration were analysed. The most prominent vacuolar degeneration in hepatocytes in the aspects of presence, area and perimeter was observed in rats exposed to tacrolimus, mycophenolate mofetil and glucocorticoids, and cyclosporine A, everolimus with glucocorticoids.This is the first study that demonstrates the results of the influence of multidrug immnunosuppression distributed in utero on the hepatic tissue of offspring.

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“…Generally, a reduction in Akt phosphorylation and serum FGF21 level leads to the attenuation of insulin signaling, which impairs glucose homeostasis and enhances IR [33,39]. GLUT4 facilitates insulin-promoted glucose uptake into adipose tissue and muscle, and reduced GLUT4 expression levels lower insulin-mediated glucose uptake; exacerbated hyperglycemia may be the mechanism of action, as indicated by heightened glucose intolerance on the basis of an IPGTT [70]. Considerable basal glucose transport reductions suggest strong IR and glucose intolerance in mice that have diabetes and a selective deficiency of GLUT4 in their muscles [33].…”

Section: Discussionmentioning

confidence: 99%

Imipramine Accelerates Nonalcoholic Fatty Liver Disease, Renal Impairment, Diabetic Retinopathy, Insulin Resistance, and Urinary Chromium Loss in Obese Mice

Chang

Hou

Wang

et al. 2021

Veterinary Sciences

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Imipramine is a tricyclic antidepressant that has been approved for treating depression and anxiety in patients and animals and that has relatively mild side effects. However, the mechanisms of imipramine-associated disruption to metabolism and negative hepatic, renal, and retinal effects are not well defined. In this study, we evaluated C57BL6/J mice subjected to a high-fat diet (HFD) to study imipramine’s influences on obesity, fatty liver scores, glucose homeostasis, hepatic damage, distribution of chromium, and retinal/renal impairments. Obese mice receiving imipramine treatment had higher body, epididymal fat pad, and liver weights; higher serum triglyceride, aspartate and alanine aminotransferase, creatinine, blood urea nitrogen, renal antioxidant enzyme, and hepatic triglyceride levels; higher daily food efficiency; and higher expression levels of a marker of fatty acid regulation in the liver compared with the controls also fed an HFD. Furthermore, the obese mice that received imipramine treatment exhibited insulin resistance, worse glucose intolerance, decreased glucose transporter 4 expression and Akt phosphorylation levels, and increased chromium loss through urine. In addition, the treatment group exhibited considerably greater liver damage and higher fatty liver scores, paralleling the increases in patatin-like phospholipid domain containing protein 3 and the mRNA levels of sterol regulatory element-binding protein 1 and fatty acid-binding protein 4. Retinal injury worsened in imipramine-treated mice; decreases in retinal cell layer organization and retinal thickness and increases in nuclear factor κB and inducible nitric oxide synthase levels were observed. We conclude that administration of imipramine may result in the exacerbation of nonalcoholic fatty liver disease, diabetes, diabetic retinopathy, and kidney injury.

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Chronic everolimus treatment of high‐fat diet mice leads to a reduction in obesity but impaired glucose tolerance

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 9 publications

References 57 publications

The Effect of Dietary Fat and Sucrose on Cognitive Functioning in Mice Lacking Insulin Signaling in Neuropeptide Y Neurons

The Effect of Dietary Fat and Sucrose on Cognitive Functioning in Mice Lacking Insulin Signaling in Neuropeptide Y Neurons

Prenatal Exposition to Different Immunosuppressive Protocols Results in Vacuolar Degeneration of Hepatocytes

Imipramine Accelerates Nonalcoholic Fatty Liver Disease, Renal Impairment, Diabetic Retinopathy, Insulin Resistance, and Urinary Chromium Loss in Obese Mice

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