Murine Models of Obesity

Martins, Tânia; Castro-Ribeiro, Catarina; Lemos, Sílvia; Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Rosa, Eduardo; Oliveira, Paula A.; Antunes, Luís

doi:10.3390/obesities2020012

Cited by 15 publications

(6 citation statements)

References 168 publications

(341 reference statements)

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“…42,54 In fact, these models reproduce key morphological, biochemical, and molecular features of the corresponding human condition. 42,55 Spermatogenesis is a key process in male reproduction, involving many cellular (somatic cell populations, Leydig, Sertoli, and peritubular myoid cells) and molecular (gonadotropins, testosterone, and estrogen) players, which are essential factors in a process that culminates on differentiation of the germinative epithelium to mature sperm cells. 56,57 This complex process can be severely impaired by external conditions, including WD intake and its resulting comorbidities.…”

Section: Discussionmentioning

confidence: 99%

A mixture of glyphosate and 2,4‐D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice

Valente,

de Matos Manoel,

Reis

et al. 2023

Environmental Toxicology

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The consumption of Western diet (WD) – enriched in fats and sugars – is associated with overweight, obesity and male reproductive disorders. In addition to WD intake, crops and dairy products display residues of herbicides, including glyphosate and 2,4‐D that are widely applied worldwide. The concomitant exposure to WD and herbicides – mimicking contemporary scenarios – is not fully investigated. Thus, we evaluated the effects of glyphosate and 2,4‐D, alone or in mixture, on WD‐induced alterations in the male genital system. Male C57BL6J mice were submitted to WD (chow containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D‐fructose and D‐glucose) for 6 months. Concomitantly to WD, the animals received glyphosate (0.05, 5, or 50 mg/kg/day), 2,4‐D (0.02, 2 or 20 mg/kg/day) or their mixture (0, 05 + 0.02, 5 + 2, or 50 + 20 mg/kg/day) by intragastrical administration (5×/week). Doses were based on Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) values. Herbicide exposure did not alter the WD‐induced obesity, hypercholesterolemia and hyperglycemia. WD induced sperm cell abnormalities, reduced the number, volume and area of Leydig cells, enhanced the frequency of epididymal abnormalities, decreased the proliferation in both germinal and epididymal epithelia, and reduced the number of androgen receptor (AR) positive epididymal cells. Remarkably, the herbicide mixtures promoted such WD‐induced effects: increased the frequency of sperm cell and epididymal abnormalities (absence of sperm, cytoplasmic vacuoles, and clear cell hypertrophy) (5 + 2 and 50 + 20 doses); decreased Leydig cell nuclei volume and area (5 + 2 and 50 + 20 doses), reduced epididymal cell proliferation (all mixtures), and AR expression (50 + 20 dose). In addition, herbicide mixtures reduced serum testosterone levels (5 + 2 and 50 + 20 doses). Our findings indicate that the mixture of glyphosate and 2,4‐D herbicides, mimicking environmentally relevant scenarios, promotes WD‐induced changes in the male genital system.

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Section: Discussionmentioning

confidence: 99%

A mixture of glyphosate and 2,4‐D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice

Valente,

de Matos Manoel,

Reis

et al. 2023

Environmental Toxicology

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“…Preclinical animal models have been broadly applied to study the underlying cellular and molecular mechanisms of obesity and to evaluate the treatment effectiveness of medicines. The murine models of obesity have been well-summarized in another paper [ 165 ].…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

The Related Metabolic Diseases and Treatments of Obesity

2022

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Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting more than 1 billion people worldwide. Obesity is commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, chronic kidney disease, and cancers. Factors such as a sedentary lifestyle, overnutrition, socioeconomic status, and other environmental and genetic conditions can cause obesity. Many molecules and signaling pathways are involved in the pathogenesis of obesity, such as nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled receptors (GPCRs), programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and sirtuin 1 (SIRT1). Commonly used strategies of obesity management and treatment include exercise and dietary change or restriction for the early stage of obesity, bariatric surgery for server obesity, and Food and Drug Administration (FDA)-approved medicines such as semaglutide and liraglutide that can be used as monotherapy or as a synergistic treatment. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gut microbiota plays an important role in obesity and its comorbidities, and gut microbial reprogramming by fecal microbiota transplantation (FMT), probiotics, prebiotics, or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are ongoing to evaluate the therapeutic effects of different treatments. Currently, prevention and early treatment of obesity are the best options to prevent its progression to many comorbidities.

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“…These models have low mortality and may closely resemble the human surgical procedures in that post-operative outcomes may be observed that allow for evaluation of the physiological effects of bariatric surgery in obese mice and rats. Obesity in rodents may be induced using high fat, high carbohydrate or Western "cafeteria" diets (25), which stimulates significantly altered immune responses (26), gut microbiota changes (27) and inherent airway hyperresponsiveness (28). When combined with acute or chronic allergic challenge, models of obesity demonstrate that marked changes to pulmonary inflammation, remodeling and responsiveness occur that are distinct from changes induced by allergen exposures alone (26).…”

Section: Introductionmentioning

confidence: 99%

Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity

Womble¹,

Ihrie²,

Mcquade³

et al. 2023

Front. Endocrinol.

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IntroductionAsthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of beta-2-adrenergic agonists and inhaled corticosteroids; however, a subset of patients with comorbid obesity experience resistance to currently available therapeutics. Patients with asthma and comorbid obesity are also at a greater risk for severe disease, contributing to increased risk of hospitalization. Bariatric surgery improves asthma control and airway hyperresponsiveness in patients with asthma and comorbid obesity, however, the underlying mechanisms for these improvements remain to be elucidated. We hypothesized that vertical sleeve gastrectomy (VSG), a model of metabolic surgery in mice, would improve glucose tolerance and airway inflammation, resistance, and fibrosis induced by chronic allergen challenge and obesity.MethodsMale C57BL/6J mice were fed a high fat diet (HFD) for 13 weeks with intermittent house dust mite (HDM) allergen administration to induce allergic asthma, or saline as control. At week 11, a subset of mice underwent VSG or Sham surgery with one week recovery. A separate group of mice did not undergo surgery. Mice were then challenged with HDM or saline along with concurrent HFD feeding for 1-1.5 weeks before measurement of lung mechanics and harvesting of tissues, both of which occurred 24 hours after the final HDM challenge. Systemic and pulmonary cytokine profiles, lung histology and gene expression were analyzed.ResultsHigh fat diet contributed to increased body weight, serum leptin levels and development of glucose intolerance for both HDM and saline treatment groups. When compared to saline-treated mice, HDM-challenged mice exhibited greater weight gain. VSG improved glucose tolerance in both saline and HDM-challenged mice. HDM-challenged VSG mice exhibited an increase in airway hyperresponsiveness to methacholine when compared to the non-surgery group.DiscussionThe data presented here indicate increased airway hyperresponsiveness in allergic mice undergoing bariatric surgery.

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Murine Models of Obesity

Cited by 15 publications

References 168 publications

A mixture of glyphosate and 2,4‐D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice

A mixture of glyphosate and 2,4‐D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice

The Related Metabolic Diseases and Treatments of Obesity

Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity

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