Genistein activated adenosine 5'-monophosphate-activated protein kinase-sirtuin1/peroxisome proliferator-activated receptor γ coactivator-1α pathway potentially through adiponectin and estrogen receptor ß signaling to suppress fat deposition in broiler chickens.

Genistein can be used as a dietary additive to control fat deposition in animals, while its mechanism is poorly understood. In this study, a total of 144 male broilers were randomly divided into 4 groups. Birds were fed standard diets supplemented with 0, 50, 100 or 150 mg of genistein/kg from 21 to 42 d of age. Results showed that genistein treatment decreased the relative weight of abdominal fat and triglyceride contents in broiler chickens. Genistein downregulated hepatic lipid droplets accumulation and upregulated the activity of lipoprotein lipase and hepatic lipase and the concentration of adiponectin. Furthermore, the liver X receptor α, sterol regulatory element-binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA expressions were decreased, whereas adiponectin receptor 2, peroxisome proliferator-activated receptor α, adipose triglyceride lipase, and carnitine palmitoyl transferase-I (CPT-I) mRNA abundances were increased in the liver of broilers treated with genistein. In addition, genistein increased the NAD+ concentration and NAD+/NADH ratio in the liver. Genistein increased estrogen receptor ß (ERß), forkhead box O1, nicotinamide phosphoribosyl transferase, sirtuin1 (SIRT1), phospho (p)-adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), p-ACC, and CPT-I protein levels, whereas the SREBP-1c and FAS levels were decreased. These data indicated that genistein might reduce fat accumulation in broiler chickens via activating the AMPK-SIRT1/PGC-1α signaling pathway. The activation of this signaling pathway might be achieved by its direct effect on improving the adiponectin secretion or its indirect effect on upregulation of ERß expression level through paracrine acting of adiponectin.

(-)-Hydroxycitric acid regulates energy metabolism by activation of AMPK - PGC1α - NRF1 signal pathway in primary chicken hepatocytes.

As the most important bioactive substance in Garcinia cambogia, (-)-hydroxycitric acid (HCA) is widely used in food additives to regulate obesity and diabetes in animals or humans, while the mechanism is poorly understood. The purpose of this study was to elucidate the regulatory effect and mechanism of (-)-HCA in regulating glucose and lipid metabolism in chicken primary hepatocytes. The results showed that (-)-HCA obviously decreased triglyceride content through inhibiting the fatty acid synthase protein level, and enhancing the protein level of phosphorylated acetyl CoA carboxylase, enoyl coenzyme A hydratase short chain 1 and carnitine palmitoyltransferase 1A in hepatocytes. Moreover, (-)-HCA markedly enhanced the protein level of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase A and complex IV, and which led to the enhancing of glucose uptake and catabolism in hepatocytes. Importantly, the regulation of (-)-HCA on these key factors associated with lipid and glucose metabolism in hepatocytes was mainly achieved through activation of AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α-nuclear respiratory factor 1 signaling pathway. These results convincingly demonstrated the mechanism of (-)-HCA's regulating on glucose and lipid metabolism, and provided a strategy in prevention of diseases associated with glycolipid metabolic abnormalities in animals, even in humans.

Effect of dehydroepiandrosterone on the immune response and gut microbiota in dextran sulfate sodium-induced colitis mice.

Dehydroepiandrosterone (DHEA) possess anti-inflammatory, anti-oxidant and immune-regulating function in animals and humans, but there is not enough information about the mechanisms underlying its beneficial effects. The present study investigated the effect and mechanism of DHEA in dextran sulfate sodium (DSS)-induced colitis mice. The findings showed that DHEA relieved the decreasing of body weight, the increasing of disease activity index, the enhancing of spleen weight, the shortening of colon length and the rising of myeloperoxidase activity; meanwhile, histopathological analysis showed that DHEA maintained a relatively intact structure of colon in DSS-induced colitis mice. DHEA decreased the malondialdehyde content, superoxide dismutase activity and inducible nitric oxide synthase protein level; meanwhile, DHEA also inhibited the secretion of tumor necrosis factor-α, interleukin-1ß and interleukin-6 in DSS-induced colitis mice. Importantly, our results showed that DHEA blocked the activation of nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways; and it inhibited the Nod-like receptor protein 3 inflammasome activation in DSS-induced colitis mice. Furthermore, DHEA markedly promoted the intestinal barrier function by up-regulation zonula occludens-1 expression level. The 16S rDNA gene sequencing demonstrated that DHEA decreased the Pseudomonas abundance in DSS-induced colitis mice. In conclusion, our data demonstrated that DHEA reduces oxidative damage through regulating antioxidant enzyme activity; inhibits pro-inflammatory cytokines production by blocking the activation of p38 MAPK and NF-κB signal pathway; protects colon barrier integrity via increasing tight junction protein expression and modulating gut microbiota taxa; all that finally alleviates DSS-induced experimental colitis in mice.

(-)-Hydroxycitric Acid Influenced Fat Metabolism via Modulating of Glucose-6-phosphate Isomerase Expression in Chicken Embryos.

The current research aimed to explore the impact of (-)-hydroxycitric acid (HCA) on fat metabolism and investigate whether this action of (-)-HCA was associated with modulation of glucose-6-phosphote isomerase (GPI) expression in chicken embryos. We constructed a recombinant plasmid (sh2-GPI) to inhibit GPI expression, and then embryos were treated with (-)-HCA. Results showed that (-)-HCA reduced lipid droplet accumulation, triglyceride content, and lipogenesis factors mRNA level and increased lipolysis factors mRNA expression, while this effect caused by (-)-HCA was markedly reversed when the chicken embryos were pretreated with sh2-GPI. (-)-HCA increased phospho (p)-acetyl-CoA carboxylase, enoyl-CoA hydratase short chain-1, carnitine palmitoyl transferase 1A, p-AMP-activated protein kinase, and peroxisome proliferators-activated receptor α protein expression, and this action of (-)-HCA also dispelled when the chicken embryos were pretreated with sh2-GPI. These data demonstrated that (-)-HCA decreased fat deposition via activation of the AMPK pathway, and the fat-reduction action of (-)-HCA was due to the increasing of GPI expression in chicken embryos.

Potential role of ALDH3A2 on the lipid and glucose metabolism regulated by (-)-hydroxycitric acid in chicken embryos.

This study aimed to investigate the effect of (-)-hydroxycitric acid ((-)-HCA) on lipid and glucose metabolism, and further analyzed these actions whether associated with modulation of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) expression in chicken embryos. Results showed that (-)-HCA decreased triglyceride content and lipid droplet counts, while these effects induced by (-)-HCA were reversed in chicken embryos pre-transfected with sh4-ALDH3A2. (-)-HCA decreased malic enzyme, acetyl-CoA carboxylase, fatty acid synthase, and sterol regulatory element binding protein-1c mRNA level, while increased carnitine palmitoyl transferase 1A (CPT1A) and peroxisome proliferators-activated receptor α (PPARα) mRNA level; and the action of (-)-HCA on lipid metabolism factors had completely eliminated in embryos pre-transfected with sh4-ALDH3A2. Chicken embryos pre-transfected with sh4-ALDH3A2 had eliminated the increasing of serum glucose and hepatic glycogen content induced by (-)-HCA. (-)-HCA decreased phosphofructokinase-1 and increased G6P, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate carboxylase mRNA level in chicken embryos. Similarly, the effect of (-)-HCA on these key enzyme mRNA level was reversed in embryos pre-transfected with sh4-ALDH3A2. Furthermore, (-)-HCA increased PPAR-γ-coactivator-1α (PGC-1α), PPARα, hepatic nuclear factor-4A, PEPCK, and CPT1A protein level, and these actions of (-)-HCA disappeared in embryos pre-transfected with sh4-ALDH3A2. These results indicated that (-)-HCA reduced fat accumulation and accelerated gluconeogenesis via activation of PGC-1α signaling pathway, and these effects of (-)-HCA might associate with the increasing of ALDH3A2 expression level in chicken embryos.

(-)-Hydroxycitric Acid Suppresses Lipid Droplet Accumulation and Accelerates Energy Metabolism via Activation of the Adiponectin-AMPK Signaling Pathway in Broiler Chickens.

(-)-Hydroxycitric acid (HCA) inhibits the deposition of fat in animals and humans, while the molecular mechanism is still unclear. The present study investigated the effect and mechanism of (-)-HCA's regulation of lipid, glucose, and energy metabolism in broiler chickens. The current results showed that (-)-HCA decreased the accumulation of lipid droplets and triglyceride content by reducing fatty acid synthase protein level and enhancing phosphorylation of acetyl-CoA carboxylase protein level. (-)-HCA accelerated carbohydrate aerobic metabolisms by increasing the activities of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. Furthermore, (-)-HCA increased adiponectin receptor 1 mRNA level and enhanced phospho-AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A protein levels in broiler chickens. These data indicated that (-)-HCA reduced lipid droplet accumulation, improved glucose catabolism, and accelerated energy metabolism in broiler chickens, possibly via activation of adiponectin-AMPK signaling pathway. These results revealed the biochemical mechanism of (-)-HCA-mediated fat accumulation and the prevention of metabolic disorder-related diseases in broiler chickens.