An impaired hepatic clock system effects lipid metabolism in rats with nephropathy

Abstract

Hyperlipidemia is a key clinical feature in patients with nephrotic syndrome (NS) that is associated with the incidence of cardiovascular events. Recent studies have suggested that the disorders of triglycerides, gluconeogenesis and liver glucose metabolism are associated with the abnormal transcription of clock genes. However, changes to the circadian rhythm of blood lipids in NS require further exploration, and the effects of NS on the hepatic clock system remain to be elucidated. In the present study, the impaired diurnal rhythm of the hepatic core clock genes (BMAL1, CLOCK, CRY1, CRY2, PER1 and PER2) significantly induced circadian rhythm abnormalities in liver-specific clock-controlled genes (LXR, CYP7A1, SREBP-1, ABCA1, DEC1 and DEC2; all P<0.05), which were significantly associated with the abnormal diurnal rhythms of triglyceride, total cholesterol, aspartate aminotransferase and alanine aminotransferase (all P<0.05) in rats with Adriamycin-induced nephropathy. Furthermore, a protein-protein interaction network was identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses based on the human database was conducted to obtain signaling pathway and correlation prediction analyses of overall human clock and clock-controlled gene correlations. Strong correlations of the aforementioned clock genes were detected (avg. local clustering coefficient, 0.849) which suggested significant enrichment in circadian rhythm signaling. The present results indicated that damage to hepatic clock systems may impact blood lipid circadian rhythm disorders in NS, and offer a starting point for understanding the crosstalk between peripheral organs and peripheral clock systems.

Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review

“…This is particularly problematic when animals treated with different diets are culled at different times over the day as this would dramatically alter the results and lead to erroneous interpretation [17]. The circadian control of Cyp7a1 , along with other clock associated genes, has also been shown to parallel changes in triglyceride and total cholesterol [18]. A summary of circadian genes involved in the regulation of Cyp7a1 is shown in Table 1.…”

Intestinal Flora Derived Metabolites Affect the Occurrence and Development of Cardiovascular Disease

“… 62 To be specific, the acidic pathway is that cholesterol is catalyzed by CYP7A1 to produce 7α hydroxycholesterol, which in turn catalyzes the production of primary bile acid as the initial product, namely chenodeoxycholic acid (CDCA) and cholic acid (CA), which then bind to glycine and taurine, followed by concentration and storage in the gallbladder. 63 Previous studies have shown that CYP7A1 is regulated by dietary cholesterol, 64 circadian rhythm, 65 transcription factors, 66 and microRNAs. 67 , 68 In the ileum, the conjugated bile acids are reabsorbed and transported to the liver through the portal vein, which is called enterohepatic circulation.…”

Elucidation of clinical implications Arising from circadian rhythm and insights into the tumor immune landscape in breast cancer

“…The circadian rhythm is a 24-h endogenous rhythm established by organisms to adapt to the Earth's rotation. As an important regulatory system for the maintenance of normal cell and tissue homeostasis, circadian rhythm plays a key role in processes associated with cancer [ [18] , [19] , [20] , [21] ]. This rhythm depends on the production of circadian genes and proteins regulated by the circadian clock.…”