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

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.

Evaluation of feeding periods of dietary conjugated linoleic acid supplementation on growth performance, nutrient digestibility, blood profiles, and meat quality in finishing pigs

This study was conducted to evaluate feeding periods of dietary conjugated linoleic acid (CLA) supplementation on growth performance, nutrient digestibility, blood profiles, and meat quality in finishing pigs. A total of 150 finishing pigs [(Yorkshire × Landrace) × Duroc] with an average body weight (BW) of 83.13 ± 1.91 kg were randomly allocated into one of three treatments (10 pens per treatment, five pigs per pen) based on their BW. Dietary treatments consisted of supplementing the basal diet with 1.0% CLA during 2, 3, and 4 wk prior to finishing. Pigs fed CLA diets 2 wk before finishing had a higher overall average daily gain (ADG) and gain-to-feed ratio (G/F) than those fed CLA diets 4 wk before finishing (P < 0.05). In the whole experiment, pigs fed CLA diets 2 wk before finishing had a higher serum low-density lipoprotein (LDL) than those fed CLA diets 3 and 4 wk before finishing. However, pigs that received CLA diets 4 wk before finishing had higher triglyceride levels (P < 0.05). Feeding 1% CLA diets 4 wk before finishing improved meat color and firmness. Taken together, feeding 1% CLA diet 4 wk before finishing increased ADG, G/F, and serum LDL, but reduced serum triglyceride.

Effect of dietary conjugated linoleic acid supplementation during late gestation on colostrum yield, fatty acid composition, and IgG concentrations in primiparous sows

This experiment was conducted to evaluate the effects of dietary conjugated linoleic acid (CLA) supplementation during late gestation on reproductive performance, colostrum yield, colostral fatty acid composition, and immunoglobulin G (IgG) concentrations in primiparous sows. Twenty-four primiparous Landrace × Large White pregnant sows were randomly selected and assigned to four dietary treatments: 0% (control), 0.75%, 1.50%, and 2.25% CLA supplementation from day 85 of gestation to parturition. During lactation, all sows were fed the same commercial diet. The preweaning mortality of suckling piglets born to dams fed supplemental CLA did decrease linearly (P = 0.01) during lactation. Administration of CLA during gestation increased linearly (P < 0.01) total saturated fatty acids and decreased linearly (P < 0.01) monounsaturated fatty acids and polyunsaturated fatty acids in colostrum. The concentrations of CLA isomers were higher (P < 0.01) in colostrum from primiparous sows fed CLA diets than in the control group. Feeding CLA increased (P < 0.05) colostral IgG concentrations, as well as that in the serum of neonatal piglets. In conclusion, 2.25% CLA supplementation in the diet of primiparous sows during late gestation could improve the passive immunity through colostral IgG and the survival of suckling piglets.