To control these diseases, research in rodent models that closely mimic. Rodent models of metabolic syndrome have significantly advanced our understanding of this. A mouse model of the metabolic syndrome american diabetes. Hasty 1, 1 departments of molecular physiology and biophysics, vanderbilt university. Differential effects of diet and geneticallyinduced.
The prevalence of metabolic syndrome varies by defini tion used and population studied. Metabolic syndrome, obesity, high fat diet, genetic model. Metabolic syndrome markers in wistar rats of different. Metabolomics of oncogenespecific metabolic reprogramming. The most frequently used animal model to study these atherogenic processes and interorgan. Oct 17, 2019 source data are provided as a source data file. Molecular models of metabolic syndrome authorstream presentation. It is one of few models that combine many aspects of metabolic syndrome and can be useful for testing new therapeutic approaches for combating obesity complications, particularly cardiomyopathy. Mice with hyperlong telomeres show less metabolic aging and. Insulin signaling, resistance, and metabolic syndrome. Being a multifactorial condition with alarming rate of prevalence nowadays, establishment of appropriate experimental animal. Background and aims increased efficiency of energy harvest, due to alterations in the gut microbiota increased firmicutes and decreased bacteroidetes, has been implicated in obesity in mice and humans. Mouse models of metabolic liver injury article pdf available in laboratory animals 491 suppl. Animal models have enriched understanding of the physiological basis of metabolic disorders and advanced identification of genetic risk factors underlying the metabolic syndrome mets.
Animal models provide an opportunity to examine correlations among different metabolic parameters to understand why metabolic complications sometimes cluster and sometimes do not. Cardiac metabolic pathways affected in the mouse model of. Klinefelter syndrome ks, caused by xxy karyotype, is characterized by low testosterone, infertility, cognitive deficits, and increased prevalence of health problems including obesity and diabetes. Cardiolipin cl is a mitochondrial phospholipid essential for electron transport chain etc integrity. May 05, 2020 peripheral cb1 receptor antagonist for therapeutic use in metabolic syndrome obesity has dramatically increased in the united states in recent decades. It has been difficult to separate direct genetic effects from hormonal effects in human studies or in mouse models of ks because low testosterone levels are confounded. The intestines of obese humans and mice are enriched with erysipelotrichi, a class within the firmicutes.
Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome. Oncogenespecific metabolic reprogramming during breast cancer some of the oncogenespecific metabolic profiles are consistent with known phenotypes and signaling pathways of the specific oncogenes. At 6 months of age, wild type, apoe and apoearko c57bl6 mice were inoculated with the murine breast cancer cell line e0771. The sex chromosome trisomy mouse model of xxy and xyy.
Of mouse models of mast cell deficiency and metabolic syndrome. Hasty 1, 1 departments of molecular physiology and biophysics, vanderbilt university medical center, nashville, tn 37232, usa. Parasitic nematodeinduced modulation of body weight and. Composition and energy harvesting capacity of the gut.
Frontiers mouse models for atherosclerosis research. Metabolic syndrome components in murine models bentham. Reprinted with permission from animallabnews march 2007. The proadipogenic and metabolic effects of dht in our mouse model may also be partly explained by the absence of estrogen production by the noncycling ovaries, because it has been shown that a lack of estrogens or estrogen receptor.
Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Metabolic abnormalities in williamsbeuren syndrome journal. Jci chop deletion reduces oxidative stress, improves. Basal blood glucose level at 25 weeks and the intraperitoneal glucose tolerance test in 11weekold mice showed no significant differences between wt animals and. The double knockout apoearko mouse displays all features of metabolic syndrome. Tsh was measured in all mouse models at 25 weeks of age.
Therefore, we explored the effect of a highfat hf diet and genetically determined. A panel for early detection, management, and risk stratification in the west virginian population krithika srikanthan 1, andrew feyh, haresh visweshwar, joseph i. A mouse model of the metabolic syndrome the metabolic syndrome syndro the metabolic syndrome syndrome x is a cluster of risk factors for cardiovascular disease and type 2 diabetes, that includes hypertension, obesity, insulin resistance, and dyslipidemia. Mouse models of the metabolic syndrome pdf download mouse models of the metabolic syndrome pdf read online computational modeling of metabolic syndrome can provide new insights into its development, but previous the researchers found that their modeling approach correctly predicted progression of metabolic syndrome in the mice, as well as development of comorbidities, such as fatty liver. Mouse models of the metabolic syndrome disease models.
Development of a metabolic syndrome mouse model of reast. Metabolic syndrome mets is a clustering of metabolic complications representing a premorbid condition that is a substantial public health burden. Frontiers mouse models for atherosclerosis researchwhich. Atp iii, adult treatment panel iii based on the national cholesterol education. A model of metabolic syndrome and related diseases with.
The precise definition of mets, the relationships of its metabolic features, and what initiates it, are debated. This chronic immunometabolic disease evolves during decades in humans and encompasses different organs and immune cell types, as well as local and systemic processes that promote the progression of the disease. Metabolic abnormalities in williamsbeuren syndrome. Mitochondria dysfunction is often described as a cause of cardiac impairment but its extent may depend on the type of experimental diabetes. Cldeficiency in humans is caused by mutations in the tafazzin taz gene and results in a multisystem pediatric disorder, barth syndrome bths. The use of mouse models in medical research has greatly contributed to our understanding of the development of type 2 diabetes mellitus and the mechanisms of disease progression in the context of insulin resistance and. In ovariectomized mice, a model of postmenopausal obesity. Highfat diets for dietinduced obesity models in order to gain a greater understanding of human obesity, rats and mice are commonly used models as they will readily gain weight when provided with a highfat diet and also develop other risk factors associated with the ms.
Parasitic nematode infection induces a polarized th2 cytokine response and has been explored to treat autoimmune diseases. Noninvasive liquid diet delivery of stable isotopes into. Apr 12, 2019 atherosclerosis is one of the primary causes of cardiovascular disease and mortality. Hasty 1, 1 departments of molecular physiology and biophysics, vanderbilt. Murine models are especially appropriate for this type of research, and are an excellent resource not only for identifying candidate genomic regions. Pdf metabolic syndrome mets consists of several medical conditions that collectively predict the risk for cardiovascular disease better than. Brief summary of dietinduced metabolic disease models. Here, we report a noninvasive method of administering c 6glucose to mouse models via liquid diet feeding to achieve deep metabolic network coverage. The gut microbiome is altered in a letrozoleinduced mouse. We investigated the effects of nematode infection against obesity and the associated metabolic. In ovariectomized mice, a model of postmenopausal obesity, g1 agonist treatment increased energy. As with fructose, sucrose induced lipogenesis in rats along with increased plasma concentrations of insulin. The metabolic syndrome is an emerging global epidemic characterized by clustering of metabolic abnormalities leading to increased cardiovascular risk. The quest continues article pdf available in journal of applied physiology 102 6.
Background williamsbeuren syndrome wbs, omim194050 is a neurodevelopmental disorder with multisystemic manifestations caused by a 1. Modelling agerelated metabolic disorders in the mouse. A new mouse model of metabolic syndrome and associated. Mouse models of the metabolic syndrome pdf vrcollector. Peripheral cb1 receptor antagonist for therapeutic use in. Clostridium ramosum, a member of the erysipelotrichi, has been linked to symptoms of the metabolic syndrome. Previous studies in multiple ad mouse models have altogether shown the exacerbation of amyloid pathology by dietinduced metabolic abnormalities. It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex. Animal models and programming of the metabolic syndrome. Dietinduced metabolic syndrome in rodent models angela m. Both environmental and genetic factors are thought to play a role in the etiology of. Atherosclerosis is one of the primary causes of cardiovascular disease and mortality. Longitudinal studies in humans have several limitations due to the invasive nature of certain analyses and the size and randomness of the study populations. Clostridium ramosum promotes highfat dietinduced obesity in.
The risk of developing mets in human depends on synergy of both genetic and environmental factors. Attenuation of metabolic syndrome in the obob mouse model by resistant starch intervention is dose dependent anqi wang, a min liu, a wenting shang, a jinguang liu, a zhen dai, a padraig strappe b and zhongkai zhou ac. To adapt and validate the clarke and gold questionnaires and the edinburgh hypoglycemia symptom scale ehss to brazilian portuguese. Peripheral cb1 receptor antagonist for therapeutic use in metabolic syndrome obesity has dramatically increased in the united states in recent decades. Thus, the suppression of class iia hdacs in mouse models of type 2 diabetes.
Dehydroepiandrosterone dhea has been widely used to generate pcos animal models in mice and rats 8. Recently, reports of the application of this technique in conscious, unrestrained mice have increased and have the potential to widen its use to many transgenic mouse models of metabolic disorders, as covered in further detail by several. Highfat diet induces significant metabolic disorders in a. Comments that contribute to the discussion of the article will be posted. Metabolic syndrome model includes miniature brain, heart, kidney, liver, artery, pancreas. Development of a metabolic syndrome mouse model of reast ancer. Effects of some treatment strategies on rodent models of metabolic syndrome. Lu d, willard d, patel ir, kadwell s, overton l, kost t, luther m, chen w, woychik rp, wilkison wo, et al.
The nmf15 mouse model provides a new entry point into pathways mediating leptin resistance and obesity. Animal models of dietinduced metabolic syndrome have classically. Reported endocrine and metabolic abnormalities include transient hypercalcaemia of infancy, subclinical hypothyroidism in. The large intestine contains a complex community of microorganisms the gut microbiome that is dysregulated in humans with obesity and type 2 diabetes. Frontiers the vascular consequences of metabolic syndrome. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. In both genetic and dietinduced models of insulin resistance, chop deficiency improved. Metabolic syndrome, liver, nuclear receptors, adipokines, mouse models, gene therapy.
Obesity is associated with a chronic lowgrade inflammation characterized by increased levels of proinflammatory cytokines that are implicated in disrupted metabolic homeostasis. Edwards school of medicine, marshall university, usa 2. Thus, animal models that are able to mimic human physiological responses could aid in investigating. Here we proposed to compare drug or dietinduced models of diabetes in terms of metabolic features, cardiac and mitochondrial. Jan 29, 2020 estrogen is known to have positive effects on obesity and metabolism. Sucrose is a dietary source of fructose, thus sucrose feeding has been used to mimic human metabolic syndrome in animal models. Only pd mice had a significant increase in tsh levels compared with wt p0. Obesity can lead to a variety of complications, including insulin resistance, buildup of fat in the liver and high cholesterol. To gain a better understanding of the pathogenesis of pcos, it is important to have a suitable animal model that replicates many or most reproductive and metabolic features of this syndrome.
Estrogen is known to have positive effects on obesity and metabolism. The purpose of this study was to discuss advantages and disadvantages of different models of obesity and metabolic syndrome in rats. Independently, the components of metabolic syndrome each have the potential to affect the endothelium to cause vascular dysfunction and disrupt vascular homeostasis. Thus, determination of metabolic syndrome would be inferior to the use of a specific risk assessment method such as the diabetes predicting model, which takes family history into account. The metabolic syndrome mets is characterized by obesity concomitant with other metabolic abnormalities such as hypertriglyceridemia, reduced highdensity lipoprotein levels, elevated blood pressure and raised fasting glucose levels. In some models, changes in enzymes responsible for either a. All relevant data are within the paper and its supporting information files. Animal models and programming of the metabolic syndrome british. Methods and models for metabolic assessment in mice.
It is considered a multiplex cardiovascular risk factor, in that each component of the cluster of abnormalities is a risk factor in its own right. Reproductive and metabolic phenotype of a mouse model of. Results typical metabolic syndrome ms, nonalcoholic fatty liver disease. In fact, with the economic, technological, and agricultural developments of the last century, access to adequate food supplies is the most widespread in human history. Metabolic syndrome mets consists of several medical conditions that collectively predict the risk for cardiovascular disease better than the sum of individual conditions. Alternatively, other metabolic profiles are unique to this dataset and might point us towards new directions to study how these mouse models mimic. Preclinical efficacy of the gperselective agonist g1 in. Nov 01, 2014 to gain a better understanding of the pathogenesis of pcos, it is important to have a suitable animal model that replicates many or most reproductive and metabolic features of this syndrome.
Cardiac contractile function and mitochondrial respiration. In one study, the presence of four or more metabolic syndrome risk factors was associated with a 3. Use of mouse models in studying type 2 diabetes mellitus. In recent decades, metabolic syndrome has become a public health problem throughout the world. Similar to fructose, sucrose feeding has shown variable results, especially with obesity 116, 117.
Clostridium ramosum, a member of the erysipelotrichi, is associated with symptoms of the metabolic syndrome in humans. Being a multifactorial condition with alarming rate of prevalence nowadays, establishment of. According to the data there are dietary, genetic and pharmacological models. Attenuation of metabolic syndrome in the obob mouse model. Recently, reports of the application of this technique in conscious, unrestrained mice have increased and have the potential to widen its use to many transgenic mouse models of metabolic disorders, as covered in further detail by several recent studies ye et al. Metabolic syndrome is characterized by visceral obesity, dyslipidemia, hyperglycemia and hypertension, and affects over one billion people. Reproductive and metabolic phenotype of a mouse model of pcos. Nov 21, 2017 here, we report a noninvasive method of administering c 6glucose to mouse models via liquid diet feeding to achieve deep metabolic network coverage. Rodent models of metabolic syndrome have significantly. Pathophysiological processes underlying diabeticrelated cardiomyopathies are complex. We assessed the effect of chop deletion in multiple mouse models of type 2 diabetes and found that chop mice had improved glycemic control and expanded. Mice with hyperlong telomeres show less metabolic aging. Introduction metabolic syndrome is a complex disorder and an emerging clinical challenge.
Mets in humans, the animal models frequently rely on manipulating the. Features of the metabolic syndrome nutritionally induced ir develops as metabolic adaptation to circulating ffas from intraabdominal fat stores. Request pdf of mouse models of mast cell deficiency and metabolic syndrome guidelines for submitting commentspolicy. The application of mouse models to the studying of metabolic derangements due to overfeeding and obesity recently assumed even more importance. Gpi anatomicals 940 north shore drive lake bluff, il 60044. To clarify the possible obesogenic potential of this bacterial species and to unravel the underlying mechanism, we investigated the role of c. Metabolic syndrome components in murine models bentham science. The number of metabolic syndrome components also influences the degree of risk. Molecular models of metabolic syndrome authorstream. Women with polycystic ovary syndrome pcos have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. It has been difficult to separate direct genetic effects from hormonal effects in human studies or in mouse models of ks because low testosterone levels are confounded with sex chromosome. A valid question is whether the mouse disease models created by genetic engineering accurately reflect the clinical features of metabolic syndrome and type 2 diabetes. In general, obesity and insulin resistance ir coincide in mouse models. Clostridium ramosum promotes highfat dietinduced obesity.
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