scholarly journals Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase

Toxics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 130
Author(s):  
Oscar Samuel Ávila-Rosales ◽  
Mauricio Díaz-Muñoz ◽  
Rafael Camacho-Carranza ◽  
Elvia Coballase-Urrutia ◽  
José Pedraza-Chaverri ◽  
...  

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity.

2012 ◽  
Vol 39 (6) ◽  
pp. 7095-7104 ◽  
Author(s):  
Simone Altmann ◽  
Eduard Murani ◽  
Cornelia C. Metges ◽  
Manfred Schwerin ◽  
Klaus Wimmers ◽  
...  

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sorim Choung ◽  
Kyong Hye Joung ◽  
Bo Ram You ◽  
Sang Ki Park ◽  
Hyun Jin Kim ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.


2019 ◽  
Author(s):  
Felice Amato ◽  
Alice Castaldo ◽  
Giuseppe Castaldo ◽  
Gustavo Cernera ◽  
Gaetano Corso ◽  
...  

AbstractPatients with cystic fibrosis (CF) have low cholesterol absorption and, despite enhanced endogenous biosynthesis, low serum cholesterol. Herein, we investigated cholesterol metabolism in a murine CF model in comparison to wild type (WT) testing serum and liver surrogate biomarkers together with the hepatic expression of genes involved in cholesterol metabolism. CF mice display lower sterols absorption and increased endogenous biosynthesis. Subsequently, we evaluated the effects of a cholesterol-supplemented diet on cholesterol metabolism in CF and WT mice. The supplementation in WT mice determines biochemical changes similar to humans. Instead, CF mice with supplementation did not show significant changes, except for serum phytosterols (−50%), liver cholesterol (+35%) and TNFα mRNA expression, that resulted 5-fold higher than in CF without supplementation. However, liver cholesterol in CF mice with supplementation resulted significantly lower compared to WT supplemented mice. This study shows that in CF mice there is a vicious circle in which the altered bile salts synthesis/secretion contribute to reduce cholesterol digestion/absorption. The consequence is the enhanced liver cholesterol biosynthesis that accumulates in the cell triggering inflammation.


2019 ◽  
Vol 317 (5) ◽  
pp. R684-R695
Author(s):  
David M. Presby ◽  
L. Allyson Checkley ◽  
Matthew R. Jackman ◽  
Janine A. Higgins ◽  
Kenneth L. Jones ◽  
...  

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.


2020 ◽  
Vol 124 (4) ◽  
pp. 396-406 ◽  
Author(s):  
Hongyang Yao ◽  
Chaonan Fan ◽  
Xiuqin Fan ◽  
Yuanyuan Lu ◽  
Yuanyuan Wang ◽  
...  

AbstractAberration in leptin expression is one of the most frequent features in the onset and progression of obesity, but the underlying mechanisms are still unclear and need to be clarified. This study investigated the effects of the absence of gut microbiota on body weight and the expression and promoter methylation of the leptin. Male C57 BL/6 J germ-free (GF) and conventional (CV) mice (aged 4–5 weeks) were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for 16 weeks. Six to eight mice from each group, at 15 weeks, were administered exogenous leptin for 7 d. Leptin expression and body weight gain in GF mice were increased by NFD with more CpG sites hypermethylated at the leptin promoter, whereas there was no change with HFD, compared with CV mice. Adipose or hepatic expression of genes associated with fat synthesis (Acc1, Fas and Srebp-1c), hydrolysis and oxidation (Atgl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was lower, and hypothalamus expression of Pomc and Socs3 was higher in GF mice than levels in CV mice, particularly with NFD feeding. Exogenous leptin reduced body weight in both types of mice, with a greater effect on CV mice with NFD. Adipose Lep-R expression was up-regulated, and hepatic Fas and hypothalamic Socs3 were down-regulated in both types of mice. Expression of fat hydrolysis and oxidative genes (Atgl, Hsl, Cpt1a, Cpt1c, Ppar-α and Pgc-1α) was up-regulated in CV mice. Therefore, the effects of gut microbiota on the leptin expression and body weight were affected by dietary fat intake.


2014 ◽  
Vol 14 (1) ◽  
pp. 89-100
Author(s):  
Włodzimierz Nowak ◽  
Robert Mikuła ◽  
Ewa Pruszyńska-Oszmałek ◽  
Barbara Stefańska ◽  
Paweł Maćkowiak ◽  
...  

AbstractThe aim of the study was to investigate experimentally the effects of restricted or ad libitum feeding in the far-off period on performance of dairy cows. Two groups of Polish Holstein-Friesian cows having 19 animals in each group were allotted to two planes of nutrition in the far-off period from -56 to -22 days. The ADLIB group was fed ad libitum (DMI 12.9 kg) while in the RES group the dry matter intake was restricted by 3 kg DM compared to the average dry matter during the last 7 days in the ADLIB group. Average daily energy intake decreased from 8.90 UFL in the ADLIB to 6.83 UFL in the RES group. In the close-up period and after parturition, the cows of both groups were given the same diet. In restrictively fed cows, there was a tendency to a greater decrease in BCS during both the dry period (P=0.09) and lactation (P=0.07). After parturition milk production, fertility indices and blood concentration of IGF-1, insulin and glucose were not significantly affected by the far-off treatment. In the RES group, lower BHBA 3 days before calving and on day 5 of lactation and lower NEFA on day 28 of lactation were recorded. Also in this group higher levels of glucose 3 days before calving, triiodothyronine (T3) on days -30 and 5, and thyroxine (T4) on days -3 and 28 were observed. It is concluded that restricted feeding in the far-off period positively affected blood indicators of lipomobilization during the transition period, but had little effect on performance of lactating cows. In spite of low energy, high-fibre diet offered ad libitum in the faroff period resulted in the energy overfeeding compared to the INRA system recommendation.


2013 ◽  
Vol 221 ◽  
pp. S170
Author(s):  
Albert Braeuning ◽  
Pascal Schulthess ◽  
Alexandra Löffler ◽  
Nils Blüthgen ◽  
Michael Schwarz

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