Policosanol alleviates hepatic lipid accumulation by regulating bile acids metabolism in C57BL6/mice through AMPK-FXR-TGR5 cross-talk.

Policosanol exhibits a lipid accumulation alleviating effect, but the underlying mechanisms remains unclear. Bile acids are a significant factor in regulating cholesterol and lipid metabolism homeostasis in mammals. This study was aimed to elucidate the alleviating effect and underlying mechanisms of policosanol on hepatic lipid accumulation through bile acid (BA) metabolism. Policosanol supplementation significantly reduced hepatic triglycerides (19.29%), cholesterol (30.38%) in high fat diet (HFD) induced obese mice (P < 0.05). Furthermore, compared with the control group, HFD decreased the levels of total BAs (TBAs, 37.67%) and cholic acid (CA, 62.74%) in the serum of mice (P < 0.05). Meanwhile, compared to HFD group, policosanol also increased the level of secondary BAs (SBAs) and muricholic acids (MCAs, P < 0.05). qRT-PCR combined with protein level analysis revealed that policosanol significantly decreased sterol regulatory element-binding protein (SREBP-1c) and CD36, and increased the expression level of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 Family 27 Subfamily A Member 1 (CYP27A1, P < 0.05). Additionally, in the liver, policosanol was found downregulated the expression of farnesoid X receptor (FXR)-small heterodimer partner (SHP), and activate the Takeda G-coupled protein receptor 5 (TGR5)-adenosine-monophosphate-activated protein kinase (APMK) signaling pathway (P < 0.05). Peroxisome proliferator activated receptor (PPAR)-α, hormone sensitive lipase (HSL), and carnitine palmitoyltransferase (CPT)-1α also significantly increased in HP group (P < 0.05). The aforementioned results reveal that the potential mechanism of policosanol in alleviating liver lipid accumulation is to promote BA synthesis and lipolysis through regulating the cross-talk of the AMPK-FXR-TGR5. New insight for the application of policosanol as an anti-fatty liver functional food ingredient or supplement is also provided. PRACTICAL APPLICATION: Policosanol is an important active component of cereals and insect waxes (15-80%). However, almost no policosanol in refined foods such as clear corn germ oil and wheat flour. This study showed that oral administration of policosanol can significantly reduce triglyceride and cholesterol levels in the liver through affecting AMPK-TGR5-FXR cross-talk, whereas no significant toxicological effect is reported in human and mouse models. This study may provide theoretical support for the theory of dietary structure and the development of dietary supplements to improve lipid metabolism targeting the "bile acid-AMPK-TGR5" pathway.

Integrated Metagenomics and Metabolomics to Reveal the Effects of Policosanol on Modulating the Gut Microbiota and Lipid Metabolism in Hyperlipidemic C57BL/6 Mice.

The aim of the study was to investigate the regulatory effects of policosanol on hyperlipidemia, gut microbiota and metabolic status in a C57BL/6 mouse model. A total of 35 C57BL/6 mice were assigned to 3 groups, chow (n=12), high fat diet (HFD, n=12) and HFD+policosanol (n=11), then treated for 18 weeks. Policosanol supplementation significantly reduced serum triglycerides and total cholesterol, as well as the weight of brown adipose tissue (BAT) (p<0.05), without affecting body weight in HFD-fed mice (p>0.05). Combined 16S rRNA gene sequencing and untargeted metabolomic analysis demonstrated that policosanol had regulatory effects on gut microbiota and serum metabolism in mice. In obese mice, policosanol increased the proportion of Bacteroides, decreased the proportion of Firmicutes, and increased the ratio of Bacteroides to Firmicutes (p<0.05). Policosanol promoted lipolysis and thermogenesis process, including tricarboxylic acid (TCA) cycle and pyruvate cycle, correlated with the increasing level of Bacteroides, Parasutterella, and decreasing level of Lactobacillus and Candidatus_Saccharimonas. Moreover, policosanol decreased fatty acid synthase (FAS) in the iWAT of obese mice. Policosanol also increased peroxisome proliferators-activated receptor-γ (PPARγ), uncoupling Protein-1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PR domain containing 16 (PRDM16) in brown adipose tissue (BAT) obese mice (p<0.05). This study presents the new insight that policosanol may inhibit the synthesis of fatty acids, and promote lipolysis, thermogenesis related gene expression and regulate gut microbiota constituents, which provides potential for policosanol as an antihyperlipidemia functional food additive and provide new evidence for whole grain food to replace refined food.

Maternal dietary uridine supplementation reduces diarrhea incidence in piglets by regulating the intestinal mucosal barrier and cytokine profiles.

BACKGROUND: Nucleotides play an important role in the regulation of cellular energy and protein homeostasis, which facilitate the repair, recovery and repletion of tissue function. This study tested the effects of maternal uridine (UR) supplementation during late pregnancy and lactation of sows on the immune function of the small intestine in neonatal and suckling piglets. RESULTS: Results showed that compared to the control group, maternal dietary UR supplementation significantly decreased incidence of diarrhea in suckling piglets (P < 0.01); and increased both duodenal and ileal average villus height (P < 0.01) as well as villus height/crypt depth in ileum (P = 0.017) in neonatal piglets. RT-qPCR results showed that maternal UR supplementation decreased mRNA expression of claudin-1 in jejunum and ileum of neonatal piglets (P < 0.05), while significantly increased mRNA expression of claudin-1 in duodenum and jejunum of suckling piglets. Furthermore, in suckling piglets, maternal dietary UR supplementation increased mRNA expression of IL-6, IL-8 and IL-1ß in duodenum, jejunum and ileum (P < 0.05), increased IL-10 expression in both jejunal and ileal mucosa (P < 0.05) and increased mRNA expression of IKB and TLR4 in ileal mucosa (P < 0.05). CONCLUSIONS: These results suggest that maternal dietary supplementation with UR contributed to reducing incidence of diarrhea by regulating cytokine secretion and intestinal mucosal barrier function in suckling piglets. © 2020 Society of Chemical Industry.

Dietary arginine supplementation enhances immune responses to inactivated Pasteurella multocida vaccination in mice.

The present study was conducted to determine the adjuvant effect of arginine in mice immunised with inactivated vaccine. Mice immunised with an inactivated Pasteurella multocida vaccine and fed diets supplemented with 0·2 % (vaccine-0·2 %) or 0·5 % (vaccine-0·5 %) arginine exhibited 100 % protection from a challenge with P. multocida serotype A (CQ2) at a dose of 4·4 × 105 colony-forming units (2LD50; median lethal dose), when compared with mice receiving no arginine supplementation. Meanwhile, antibody titres in the vaccine-0·2 % arginine group were much higher than those in the vaccine-oil adjuvant group before challenge and at 36 h post-infection. Furthermore, immunisation with the inactivated vaccine and dietary supplementation with 0·2 % arginine increased serum levels of glutathione peroxidase, in comparison with immunisation with the inactivated vaccine and an oil adjuvant. Collectively, dietary arginine supplementation confers an immunostimulatory effect in mice immunised with the inactivated P. multocida vaccine. The present results also indicate that optimal supplemental doses of arginine are 0·2-0·5 % in the mouse model.