scholarly journals Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

2015 ◽  
Vol 284 (2) ◽  
pp. 101-112 ◽  
Author(s):  
Rita S. Strakovsky ◽  
Huan Wang ◽  
Nicki J. Engeseth ◽  
Jodi A. Flaws ◽  
William G. Helferich ◽  
...  
2020 ◽  
Vol 44 (11) ◽  
pp. 2323-2334
Author(s):  
Belén Chanclón ◽  
Yanling Wu ◽  
Milica Vujičić ◽  
Marco Bauzá-Thorbrügge ◽  
Elin Banke ◽  
...  

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.


2013 ◽  
Vol 109 (9) ◽  
pp. 1590-1597 ◽  
Author(s):  
Min Young Um ◽  
Mi Kyeong Moon ◽  
Jiyun Ahn ◽  
Tae Youl Ha

Coumarin is a natural compound abundant in plant-based foods such as citrus fruits, tomatoes, vegetables and green tea. Although coumarin has been reported to exhibit anti-coagulant, anti-inflammation and cholesterol-lowering properties, the effect of coumarin on hepatic lipid metabolism remains unclear. In the present study, we evaluated the ability of coumarin to protect against hepatic steatosis associated with a high-fat diet (HFD) and investigated potential mechanisms underlying this effect. C57BL/6J mice were fed a normal diet, HFD and HFD containing 0·05 % courmarin for 8 weeks. The present results showed that coumarin reduced weight gain and abdominal fat mass in mice fed the HFD for 8 weeks (P< 0·05). Coumarin also significantly reduced the HFD-induced elevation in total cholesterol, apoB, leptin and insulin (P< 0·05). In the liver of HFD-fed mice, coumarin significantly reduced total lipids, TAG and cholesterol (38, 22 and 9 % reductions, respectively; P< 0·05), as well as lipid droplet number and size. Additionally, thiobarbituric acid-reactive substance levels, as an indicator of hepatic steatosis, were attenuated by coumarin (P< 0·05). Finally, coumarin suppressed the HFD-induced up-regulation in fatty acid synthase (FAS) activity, and the expression of sterol regulatory element-binding protein-1, FAS, acetyl-CoA carboxylase 1, PPARγ and CCAAT/enhancer-binding protein-α in the liver. Taken together, these results demonstrate that coumarin could prevent HFD-induced hepatic steatosis by regulating lipogenic gene expression, suggesting potential targets for preventing hepatic steatosis.


Appetite ◽  
2011 ◽  
Vol 57 ◽  
pp. S15
Author(s):  
E.R. Ewald ◽  
B. Sun ◽  
R.H. Purcell ◽  
R.S. Lee ◽  
J.B. Potash ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100214 ◽  
Author(s):  
Marta García-Arevalo ◽  
Paloma Alonso-Magdalena ◽  
Junia Rebelo Dos Santos ◽  
Ivan Quesada ◽  
Everardo M. Carneiro ◽  
...  

2019 ◽  
Author(s):  
Ilona Binenbaum ◽  
Hanifa Abu-Toamih Atamni ◽  
Georgios Fotakis ◽  
Georgia Kontogianni ◽  
Theodoros Koutsandreas ◽  
...  

Abstract Background: The CC mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, the underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population. Results: We established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrate these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms. Conclusion: Integration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity differ in female and male mice. The clear distinction we observe in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 452-452
Author(s):  
Gavin Pierce ◽  
Mariana Buranelo Egea ◽  
Neil Shay

Abstract Objectives Red raspberries are rich in polyphenols, fiber, and volatile compounds, and have been demonstrated to have favorable effects on energy homeostasis in mice. We made two extracts from red raspberries, enriched in either hydrophilic (R25) or hydrophobic (R80) polyphenols. We tested the hypothesis that these polyphenol extracts would differentially alter and improve physiological measures and the hepatic transcriptome of C57BL/6J male mice fed a obesigenic high fat diet (HF). Methods Raspberry polyphenol extracts were obtained using FPX-66 resin, and eluting with 25% (R25) and 80% (R80) ethanol (v/v); eluates were then dried. Mice were provided a low fat diet (LF, 10% kcal fat, n = 12), high fat diet (HF, 45% kcal fat, n = 12), HF with raspberry puree concentrate (RPC, n = 8), HF with R25 (n = 8), or HF with R80 (n = 8) ad libitum for 10 weeks. Body weights, food intake, and fasting glucose levels were measured. Post mortem, serum was collected for ELISA, organ weights were recorded, and liver tissue was collected for triglyceride analysis and differential expression analysis. Results Energy efficiency and liver weights in the R25 and R80 groups were intermediate to the LF and HF controls. Fasting blood glucose, serum triglycerides, and adipose tissue weights did not differ between treatment groups. A trend toward significance was seen in reduction of weight gain in the raspberry treatment groups. Differential gene expression analysis revealed that the R25 diet acted agonistically towards the constitutive androstane receptor (CAR) and reduced the relative levels of several sterol regulatory binding protein-regulated genes. Notably, the R80 diet robustly increased levels of Cyp4a14, a peroxisome proliferator-activated receptor alpha (PPAR-α)-regulated gene. Conclusions Supplementation of a high fat diet with raspberry polyphenol extracts modified hepatic gene expression and energy efficiency in C57BL/6J mice. The two extracts had a differential impact on hepatic gene expression. For example, the R25 extract behaved as an agonist for CAR, while the R80 extract behaved as an agonist for PPAR-α. These findings suggest that select polyphenols found within red raspberries may serve as nutraceuticals that specifically act via PPAR-α, CAR, and other targets in liver. Funding Sources National Processed Raspberry Commission and Washington Red Raspberry Commission.


Sign in / Sign up

Export Citation Format

Share Document