Leptin applications in 2015

Farr, Olivia M.; Gavrieli, Anna; Mantzoros, Christos S.

doi:10.1097/med.0000000000000184

Cited by 180 publications

(87 citation statements)

References 112 publications

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“…The db/db mouse was selected because of its close representation to the phenotype observed in human diabetes and obesity. A feature of this model is hyperleptinemia from a mutation in the leptin receptor, rarely the culprit for the metabolic disturbances seen in human diabetes but nonetheless detected in diabetes 43. By including a dietary restriction component, we aimed to determine whether the defect in the OT–NP–NO system in the db/db heart could be prevented with ET.…”

Section: Discussionmentioning

confidence: 99%

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Jankowski

Gutkowska

2017

DMSO

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BackgroundRegular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)–natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity.MethodsFive-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks.ResultsAfter 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT–NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4), OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS) was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression.ConclusionOur data indicate that enhancement of eNOS by combined ET and CR may improve coronary endothelial vasodilator dysfunction in type 2 diabetes but did not prevent the downregulation of cardiac expression in the OT–NP system, possibly resulting from the sustained hyperglycemia and obesity in diabetic mice.

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Section: Discussionmentioning

confidence: 99%

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Jankowski

Gutkowska

2017

DMSO

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“…Hyperinsulinemia is a cardinal phenotype of obesity that can also lead to dysregulation of leptin signaling in adipocytes that normally acts to suppress secretion of insulin from the pancreas [112]. Leptin signaling from adipocytes serves as peripheral satiety signal and chronic elevated levels of glucocorticoids can lead to hyperleptinemia as well as to leptin resistance [113], both phenotypes associated with obesity [114]. …”

Section: Possible Mechanisms By Which Stress Exposure Alters E2’s Actmentioning

confidence: 99%

Stress-induced alterations in estradiol sensitivity increase risk for obesity in women

Michopoulos

2016

Physiology & Behavior

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The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity exclusively in females.

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“…Because this potential risk, blood pressure measurement assays were slated to be carried out immediately after efficacy testing. Although leptin treatment has since been shown to be inefficacious for weight loss in humans (16), it has been shown to have a role in the regulation of blood pressure (17). …”

Section: Resultsmentioning

confidence: 99%

ToxReporter: viewing the genome through the eyes of a toxicologist

Gosink

2016

Database

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One of the many roles of a toxicologist is to determine if an observed adverse event (AE) is related to a previously unrecognized function of a given gene/protein. Towards that end, he or she will search a variety of public and propriety databases for information linking that protein to the observed AE. However, these databases tend to present all available information about a protein, which can be overwhelming, limiting the ability to find information about the specific toxicity being investigated. ToxReporter compiles information from a broad selection of resources and limits display of the information to user-selected areas of interest. ToxReporter is a PERL-based web-application which utilizes a MySQL database to streamline this process by categorizing public and proprietary domain-derived information into predefined safety categories according to a customizable lexicon. Users can view gene information that is ‘red-flagged’ according to the safety issue under investigation. ToxReporter also uses a scoring system based on relative counts of the red-flags to rank all genes for the amount of information pertaining to each safety issue and to display their scored ranking as an easily interpretable ‘Tox-At-A-Glance’ chart. Although ToxReporter was originally developed to display safety information, its flexible design could easily be adapted to display disease information as well.Database URL: ToxReporter is freely available at https://github.com/mgosink/ToxReporter.

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Leptin applications in 2015

Cited by 180 publications

References 112 publications

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Stress-induced alterations in estradiol sensitivity increase risk for obesity in women

ToxReporter: viewing the genome through the eyes of a toxicologist

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