Implications of peroxisome proliferator-activated receptor gamma (PPARY) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice

Author(s):  
Gwyndolin M. Vail ◽  
Sabrina N. Walley ◽  
Ali Yasrebi ◽  
Angela Maeng ◽  
Thomas J. Degroat ◽  
...  
2005 ◽  
Vol 21 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Ralph L. House ◽  
Joseph P. Cassady ◽  
Eugene J. Eisen ◽  
Thomas E. Eling ◽  
Jennifer B. Collins ◽  
...  

Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice ( n = 185) were allotted to a 2 × 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) by day 14 was 12% lower in CLA- compared with LA-fed mice ( P < 0.0001). By day 14, t10c12-CLA reduced weights of epididymal, mesenteric, and brown adipose tissues, as a percentage of BW, in both lines by 30, 27, and 58%, respectively, and increased liver weight/BW by 34% ( P < 0.0001). Total RNA was isolated and pooled (4 pools per tissue per day) from epididymal adipose ( days 5 and 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides representing >20,000 genes. Numbers of genes differentially expressed by greater than or equal to twofold in epididymal adipose ( days 5 and 14) were 29 and 125, respectively. It was concluded that, in adipose tissue, CLA increased expression of uncoupling proteins (1 and 2), carnitine palmitoyltransferase system, tumor necrosis factor-α ( P < 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-γ, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 ( P < 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation.


Foods ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1494
Author(s):  
Garam Yang ◽  
Eunjeong Hong ◽  
Sejong Oh ◽  
Eungseok Kim

In this study, the role of non-viable Lactobacillus johnsonii JNU3402 (NV-LJ3402) in diet-induced obesity was investigated in mice fed a high-fat diet (HFD). To determine whether NV-LJ3402 exhibits a protective effect against diet-induced obesity, 7-week-old male C57BL/6J mice were fed a normal diet, an HFD, or an HFD with NV-LJ3402 for 14 weeks. NV-LJ3402 administration was associated with a significant reduction in body weight gain and in liver, epididymal, and inguinal white adipose tissue (WAT) and brown adipose tissue weight in HFD-fed mice. Concomitantly, NV-LJ3402 administration to HFD-fed mice also decreased the triglyceride levels in the plasma and metabolic tissues and slightly improved insulin resistance. Furthermore, NV-LJ3402 enhanced gene programming for energy dissipation in the WATs of HFD-fed mice as well as in 3T3-L1 adipocytes with increased peroxisome proliferator-activated receptor-γ (PPARγ) transcriptional activity, suggesting that the PPARγ pathway plays a key role in mediating the anti-obesity effect of NV-LJ3402 in HFD-fed mice. Furthermore, NV-LJ3402 administration in HFD-fed mice enhanced mitochondrial levels and function in WATs and also increased the body temperature upon cold exposure. Together, these results suggest that NV-LJ3402 could be safely used to develop dairy products that ameliorate diet-induced obesity and hyperlipidemia.


2014 ◽  
Vol 53 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Xiaoting Jiang ◽  
Xin Ye ◽  
Wei Guo ◽  
Hongyun Lu ◽  
Zhanguo Gao

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor whose activation is dependent on a ligand. PPARγ activation by exogenous ligands, such as thiazolidinediones (TZDs), is a strategy in the treatment of type 2 diabetes mellitus for the improvement of insulin sensitivity. In addition to a ligand, PPARγ function is also regulated by posttranslational modifications, such as phosphorylation, sumoylation, and ubiquitination. Herein, we report that the PPARγ protein is modified by acetylation, which induces the PPARγ function in the absence of an external ligand. We observed that histone deacetylase 3 (HDAC3) interacted with PPARγ to deacetylate the protein. In immunoprecipitation assays, the HDAC3 protein was associated with the PPARγ protein. Inhibition of HDAC3 using RNAi-mediated knockdown or HDAC3 inhibitor increased acetylation of the PPARγ protein. Furthermore, inhibition of HDAC3 enhanced the expression of PPARγ target genes such as adiponectin and aP2. The expression was associated with an increase in glucose uptake and insulin signaling in adipocytes. HDAC3 inhibition enhanced lipid accumulation during differentiation of adipocytes. PPARγ acetylation was also induced by pioglitazone and acetylation was required for PPARγ activation. In the absence of TZDs, the acetylation from HDAC3 inhibition was sufficient to induce the transcriptional activity of PPARγ. Treating diet-induced obesity mice with HDAC3 inhibitor or pioglitazone for 2 weeks significantly improved high-fat-diet-induced insulin resistance. Our results indicate that acetylation of PPARγ is a ligand-independent mechanism of PPARγ activation. HDAC3 inhibitor is a potential PPARγ activator for the improvement of insulin sensitivity.


2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Catherine D. Shelton ◽  
Mariana X. Byndloss

ABSTRACT In high-income countries, the leading causes of death are noncommunicable diseases (NCDs), such as obesity, cancer, and cardiovascular disease. An important feature of most NCDs is inflammation-induced gut dysbiosis characterized by a shift in the microbial community structure from obligate to facultative anaerobes such as Proteobacteria. This microbial imbalance can contribute to disease pathogenesis by either a depletion in or the production of microbiota-derived metabolites. However, little is known about the mechanism by which inflammation-mediated changes in host physiology disrupt the microbial ecosystem in our large intestine leading to disease. Recent work by our group suggests that during gut homeostasis, epithelial hypoxia derived from peroxisome proliferator-activated receptor γ (PPAR-γ)-dependent β-oxidation of microbiota-derived short-chain fatty acids limits oxygen availability in the colon, thereby maintaining a balanced microbial community. During inflammation, disruption in gut anaerobiosis drives expansion of facultative anaerobic Enterobacteriaceae, regardless of their pathogenic potential. Therefore, our research group is currently exploring the concept that dysbiosis-associated expansion of Enterobacteriaceae can be viewed as a microbial signature of epithelial dysfunction and may play a greater role in different models of NCDs, including diet-induced obesity, atherosclerosis, and inflammation-associated colorectal cancer.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ehsan Badawy ◽  
Nabila A. El-laithy ◽  
Safaa M. Morsy ◽  
Magdi N. Ashour ◽  
Tahany R. Elias ◽  
...  

Abstract Background Exercise benefits a variety of organ systems in mammals, and some of the best recognized effects of exercise on muscle are mediated by the transcriptional peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α). The regulatory effect of swimming on muscle PGC-1α, FNDC5 mRNA expression, and subsequently irisin levels is more controversial. This study aimed to investigate the role of swimming as an exercise on the expression of peroxisome proliferator-activated receptor-gamma coactivator1 alpha (PGC-1α) and Fibronectin type III domain containing 5 (FNDC5) mRNA in skeletal muscle and assessment of serum omentin, adropin, irisin, and PGC-1α levels in high carbohydrate high fat (HCHF) diet induced obesity in rats. Sixty male albino rats are randomly divided into 4 groups (15 rats/group). In the first group (control), rats are fed with standard diet. The 2nd group (cont + swim) is fed on standard diet and made swimming exercise. The 3rd group of rats is fed on HCHF, whereas in the 4th group (HCHF + swim) is also fed on HCHF diet and made swimming exercise for 20 weeks. Blood glucose, insulin, HOMA-IR, lipid profile, omentin, irisin, adropin, and PGC-1α were measured. Also, FNDC5 and PGC-1α are extracted and purified from muscle tissue samples measured by PCR test. Results Our results showed significant increase in glucose, insulin, insulin resistance, cholesterol, and triglycerides with significant decrease in omentin, irisin, adropin, PGC-1α, and HDL in HCHF group as compared to the control group. These results improved after exercise in all parameter in HCHF + swim group compare to HCHF group. Also, there was inverse correlation between omentin and fasting glucose and HOMA-IR in HCHF + swim group. Conclusions It concluded that swimming exercise improved all the above measured parameters in serum and tissues which might have been promising for the prevention of metabolic diseases.


2020 ◽  
Vol 21 (17) ◽  
pp. 6243 ◽  
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Yukihiro Miwa ◽  
Xiaoyan Jiang ◽  
Masayuki Ohta ◽  
...  

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaobo Ding ◽  
Shengjie Fan ◽  
Yan Lu ◽  
Yu Zhang ◽  
Ming Gu ◽  
...  

Obesity is a common nutritional disorder associated with type 2 diabetes, cardiovascular diseases, dyslipidemia, and certain cancers. In this study, we investigated the effects ofCitrus ichangensispeel extract (CIE) in high-fat (HF) diet-induced obesity mice. Female C57BL/6 mice were fed a chow diet or an HF diet alone or supplemented with 1% w/w CIE for 8 weeks. We found that CIE treatment could lower blood glucose level and improve glucose tolerance. In the HF+CIE group, body weight gain, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels, and liver triglyceride (TG) and TC concentrations were significantly (P<0.05) decreased relative to those in the HF group. To elucidate the mechanism of CIE on the metabolism of glucose and lipid, related genes expression in liver were examined. In liver tissue, CIE significantly decreased the mRNA expression levels of peroxisome proliferator-activated receptorγ(PPARγ) and its target genes, such as fatty acid synthase (FAS) and acyl-CoA oxidase (ACO). Moreover, CIE also decreased the expression of liver X receptor (LXR)αandβwhich are involved in lipid and glucose metabolism. These results suggest that CIE administration could alleviate obesity and related metabolic disorders in HF diet-induced obesity mice through the inhibition of PPARγand LXR signaling.


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