Per1/Per2 double knockout transcriptome analysis reveals circadian regulation of hepatic lipid metabolism

Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout(DKO)on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid(DHA)substitution. Methods and results: Both wild type(WT)and DKO male C57BL/6 mice were fed with normal chow diet(CON), HFD, or HFD with DHA substitution(AO)for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time(ZT)0(7:00 am)or ZT12(7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/-mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.

Chronic consumption of thermally processed palm oil or canola oil modified gut microflora of rats

Dietary oils have critical influences on human health,and thermally cooking or frying modify the components and nutritional functions of oils.Palm oil was the most widely used oil in food processing industry,but its health effects remain debatable.In the current study,we aimed to compare the effects of thermally oxidized palm oil and canola oil on gut microbiota.Palm oil or canola oil were heated at 180°C for 10 h to prepare high-fat diets.Rats were fed high-fat diets for 3 months,and hematological properties,gut microflora composition and intestinal gene expression were examined.The results indicated that heated canola oil consumption elevated plasma total cholesterol and LDL-c levels compared with unheated canola oil,but heated palm oil do not had these effects;and consumption of heated palm oil significantly elevated the relative abundance of Lactobacillucs and Roseburia in gut,compared with non-heated palm oil or two canola oil groups.Moreover,intestinal expression of IL-22 was increased in heated palm oil fed animal,though ZO-1 and GPR41 were reduced.In conclusion,heating process may enhance the effects of palm oil on proliferation of probiotics Lactobacillucs,and weaken the effects of canola oil on cholesterol transport and metabolism.