Animal models of obesity in rodents. An integrative review

Han

BioMed Research International

et al. 2018

To investigate the role of the peroxisome proliferator-activated receptor-γ (PPARγ) in the progression of cholesterol gallstone disease (CGD), C57bl/6J mice were randomized to the following groups (n=7/group): L (lithogenic diet, LGD), LM (LGD+pioglitazone), CM (chow diet+pioglitazone), and NC (normal control, chow diet). Gallbladder stones were observed by microscopy. Histological gallbladder changes were assessed. Bile acids (BA) and cholesterol were measured in the serum, bile, and feces. Proteins and mRNA expression of genes involved in BA metabolism and enterohepatic circulation were assessed by western blotting and real-time RT-PCR. PPARγ activation was performed in LO2 cell by lentivirus transfection and in Caco2 cell by PPARγ agonist treatment. Downregulation of farnesoid X receptor (FXR) by small interference RNA (siRNA) was performed in L02 cells and Caco2 cells, respectively. Results showed that pharmacological activation of PPARγ by pioglitazone prevents cholesterol gallstone formation by increasing biliary BA synthesis and enterohepatic circulation. Activated PPARγ induced the expression of genes involved in enterohepatic circulation and bile acid synthesis (like PCG1α, BSEP, MRP2, MRP3, MRP4, NTCP, CYP7A1, CYP27A1, ASBT, OSTα, and OSTβ). Downregulation of FXR repressed expression of partial genes involved in BA enterohepatic circulation. These findings suggest a new function of PPARγ in preventing CGD by handling BA synthesis and transport through a FXR dependent or independent pathway.

Section: Discussionsupporting

confidence: 64%

Peroxisome Proliferator-Activated Receptor-γPrevents Cholesterol Gallstone Formation in C57bl Mice by Regulating Bile Acid Synthesis and Enterohepatic Circulation

Han

BioMed Research International

et al. 2018

“…These constellations of symptoms mimic major parameters of MetS. In the literature, HF mice have been widely used to model MetS or its individual parameters such as obesity [ 56 ], prediabetes [ 38 ], hyperlipidemia [ 57 ] or MetS [ 58 ]. In the current study, HF mice did not have significant hypertriglyceridemia within the duration of our experiment at an early stage.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome

et al. 2018

Painful neuropathy (PN) is a prevalent condition in patients with metabolic syndrome (MetS). However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN) remain unclear. In the current study, high-fat-fed mice (HF mice) were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF) mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, and interleukin (IL)-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG) of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

“…Rodents which have the ability to develop obesity through genetic changes, such as leptin signaling defects (ob / ob mouse) or an autosomal recessive mutation in the fatty ( fa ) gene on chromosome 5 ( Zucker - fa / fa –fatty rat) have mainly been used [ 8 ]. In addition, hypercaloric diets are most frequently used to generate obese rodent models because they resemble the genesis of obesity in humans [ 9 ]. Cao et al (2012) [ 10 ] have demonstrated that high-fat diets vary between 30–60% of calories coming from saturated fat, such as lard, beef tallow or coconut oil, while the sugar content, for which sucrose and fructose are generally used [ 11 , 12 ] typically comprises 60–65%.…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of High Sugar, High Lard or a Combination of Both on Nutritional, Hormonal and Cardiovascular Metabolic Profiles of Rodents

et al. 2018

Background: Dietary interventions in rodents can induce an excess of adipose tissue and metabolic disorders that resemble human obesity. Nevertheless, these approaches are not standardized, and the phenotypes may vary distinctly among studies. The aim of this study was to investigate the effects of different dietary interventions on nutritional, metabolic, biochemical, hormonal, and cardiovascular profiles, as well as to add to development and characterization of an experimental model of obesity. Methods: Male Wistar rats were randomized into four groups: control diet (C), high-sugar (HS), high-fat (HF), or high-sugar and high-fat (HFHS). Weekly measurements of body weight, adiposity, area under the curve (AUC) for glucose, blood pressure (BP) and serum triglycerides, total cholesterol level, and leptin were performed. Results: HF and HFHS models were led to obesity by increases in adipose tissue deposition and the adiposity index. All hypercaloric diets presented systolic BP increases. In addition, the AUC for glucose was greater in HF and HFHS than in C, and only the HF group presented hyperleptinemia. Conclusions: HF and HFHS diet approaches promote obesity and comorbidities, and thus represent a useful tool for studying human obesity-related disorders. By contrast, the HS model did not prove to be a good model of obesity.