scholarly journals Dietary Conjugated Linoleic Acid Modulates the Hepatic Circadian Clock Program via PPARα/REV-ERBα-Mediated Chromatin Modification in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Hao-Yu Liu ◽  
Haotian Gu ◽  
Yanwei Li ◽  
Ping Hu ◽  
Yatian Yang ◽  
...  

Scope: Disruptions of circadian rhythm cause metabolic disorders and are closely related to dietary factors. In this study, we investigated the interplays between the dietary conjugated linoleic acid (CLA)-induced hepatic steatosis and the circadian clock regulation, in association with lipid homeostasis.Methods and Results: Exposure of mice to 1.5% dietary CLA for 28 days caused insulin resistance, enlarged livers, caused hepatic steatosis, and increased triglyceride levels. Transcriptional profiling showed that hepatic circadian clock genes were significantly downregulated with increased expression of the negative transcription factor, REV-ERBα. We uncovered that the nuclear receptor (NR) PPARα, as a major target of dietary CLA, drives REV-ERBα expression via its binding to key genes of the circadian clock, including Cry1 and Clock, and the recruitment of histone marks and cofactors. The PPARα or REV-ERBα inhibition blocked the physical connection of this NR pair, reduced the cobinding of PPARα and REV-ERBα to the genomic DNA response element, and abolished histone modifications in the CLA-hepatocytes. In addition, we demonstrated that CLA promotes PPARα driving REV-ERBα transcriptional activity by directly binding to the PPAR response element (PPRE) at the Nr1d1 gene.Conclusions: Our results add a layer to the understanding of the peripheral clock feedback loop, which involves the PPARα-REV-ERBα, and provide guidance for nutrients optimization in circadian physiology.

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Diwakar Vyas ◽  
Anil Kumar G. Kadegowda ◽  
Richard A. Erdman

Objective. To summarize the recent studies on effect of conjugated linoleic acid (CLA) on hepatic steatosis and hepatic and adipose lipid metabolism highlighting the potential regulatory mechanisms.Methods. Sixty-four published experiments were summarized in whichtrans-10,cis-12 CLA was fed either alone or in combination with other CLA isomers to mice, rats, hamsters, and humans were compared.Summary and Conclusions. Dietarytrans-10,cis-12 CLA induces a severe hepatic steatosis in mice with a more muted response in other species. Regardless of species, when hepatic steatosis was present, a concurrent decrease in body adiposity was observed, suggesting that hepatic lipid accumulation is a result of uptake of mobilized fatty acids (FA) from adipose tissue and the liver's inability to sufficiently increase FA oxidation and export of synthesized triglycerides. The potential role of liver FA composition, insulin secretion and sensitivity, adipokine, and inflammatory responses are discussed as potential mechanisms behind CLA-induced hepatic steatosis.


2021 ◽  
Vol 48 (2) ◽  
pp. 1359-1370
Author(s):  
Ali Jalilian ◽  
Taghi Golmohammadi ◽  
Reza Meshkani ◽  
Mehdi Koushki ◽  
Neda Eivazi ◽  
...  

2001 ◽  
Vol 86 (5) ◽  
pp. 549-555 ◽  
Author(s):  
Hyun S. Park ◽  
Ji H. Ryu ◽  
Yeong L. Ha ◽  
Jung H. Y. Park

One of the objectives of the present study was to investigate whether 1 % conjugated linoleic acid (CLA) in the diet reduced tumour incidence in the colon of 1,2-dimethylhydrazine (DMH)-treated rats. Colon cancer was induced by injecting 6-week-old, male, Sprague–Dawley rats with 15 mg/kg DMH twice per week for 6 weeks. They were fed either 1 % CLA or a control diet ad libitum for 30 weeks. Dietary CLA significantly decreased colon tumour incidence (P<0·05). Our second objective was to investigate whether apoptosis in the colon mucosa of DMH-treated rats was affected by the amount of dietary CLA and whether the changes in apoptosis were related to those in fatty acid-responsive biomarkers. For this purpose, rats were killed after being fed a diet containing 0 %, 0·5 %, 1 % or 1·5 % CLA for 14 weeks. CLA was undetected in the mucosa of rats fed the 0 % CLA diet and increased to 5·9 mg/g phospholipid in rats fed the 0·5 % diet. The apoptotic index estimated by the terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling technique was increased by 251 % and the 1,2-diacylglycerol content was decreased by 57 % in rats fed 0·5 % CLA. No further changes in these variables were observed when CLA in the diet was raised to 1·0 % or 1·5 %. However, dietary CLA decreased mucosal levels of prostaglandin E2, thromboxane B2 and arachidonic acid in a dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanisms probably involving increased apoptosis.


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