Differential expressions of hypothalamic thermosensitive TRP ion channels may underlie the posthatching ontogeny of brain cooling capacity in broiler chickens.

Two trials were performed to evaluate the association of hypothalamic abundances of thermosensitive transient receptor potential (TRP) ion channels with thermoregulation in broiler chickens. In trial 1, temporal changes in body temperatures, and hypothalamic expression patterns of TRP channels and thermoregulatory neurotransmitter concentrations were assessed from 3 to 42 d of age. In trial 2, the same variables were compared at 2 age stages between 2 distinct types of birds with high or low rectal temperatures (HRT or LRT). The core-to-brain temperature difference exhibited a rapid increase after hatching, arriving at a steady state in the fourth week (P < 0.01). The hypothalamus saw a progressive decrease of TRPV4 protein expression through 28 d (P < 0.01), followed by a great increase in the abundance of other channels right up to the end (P < 0.05). Compared to LRT birds, a decline in hypothalamic content of TRPV4 (P < 0.05), together with a bigger core-to-brain temperature difference (P < 0.01), was evident in the HRT counterpart at 33 d. In both trials, the core-to-brain and core-to-surface temperature differences were controlled in a synchronous and coordinated manner. These results allow concluding that developmental changes in the thermal sensitivity of hypothalamic neurons, determined by brain cooling capacity, involve a neuro-genomic mechanism, which regulates the ratio between thermosensitive TRP ion channels to attain a lower proportion of TRPV4 in comparison with other channels.

Reduced PGC-1ß protein expression may underlie corticosterone inhibition of mitochondrial biogenesis and oxidative phosphorylation in chicken muscles.

To uncover the molecular mechanism underlying glucocorticoid-induced loss of mitochondrial integrity in skeletal muscles, studies were performed to investigate whether the peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)-mediated pathway was involved in this process. In an in vivo trial, 3 groups of 30-d-old Arbor Acres male broilers were randomly subjected to one of the following treatments for 7 days: corticosterone (CORT, 30 mg/kg diet), control (blank), and pair-feeding (restricted to the same feed intake as for the CORT treatment), each with 6 replicates of 15 birds. Mitochondrial abundance, morphology, and function were determined in the pectoralis major and biceps femoris muscles. In an in vitro trial, a primary culture of embryonic chick myotubes was incubated with a serum-free medium for 24 h in the presence or absence of CORT (0, 200, and 1,000 nM). Results showed that CORT destroyed mitochondrial ultrastructure (p < 0.01), and decreased the enzymatic activity and protein expression of respiratory chain complexes (p < 0.05), leading to an inferior coupling efficiency (p < 0.05). As reflected by a decline in mitochondrial density (p < 0.01) and mitochondrial DNA copy number (p < 0.05), CORT reduced mitochondrial contents. Among all three PGC-1 family members, only PGC-1ß was down-regulated by CORT at the protein level (p < 0.05). Some aspects of these responses were tissue-specific and seemed to result from the depressed feed intake. Overall, CORT may impair mitochondrial biogenesis and oxidative phosphorylation in a PGC-1ß-dependent manner in chicken muscles.

Adiponectin Reduces Lipid Content in Chicken Myoblasts by Activating AMPK Signaling Pathway.

Studies in mammals have shown that adiponectin is secreted mainly by adipocytes, and it plays a crucial role in glucose and lipid metabolism in muscles. Clarifying the crosstalk role of adiponectin between adipose tissue and skeletal muscle tissue is very important for internal homeostasis. The glucose and lipid metabolism of chicken is different from that of mammals, and the role of adiponectin in chickens is unclear. Therefore, it is of great significance to study the effect and mechanism of adiponectin on lipid metabolism in chickens. In this study, the regulating effect of adiponectin on lipid metabolism in chicken myoblasts was explored by adding a certain concentration of exogenous recombinant adiponectin. Results showed that adiponectin reduced intracellular lipid content, increasing the mRNA expression of adiponectin receptor and cellular uptake of glucose and fatty acids. In addition, adiponectin activated the 5' adenosine monophosphate activated protein kinase (AMPK) signaling pathway. The above results suggested that adiponectin reduced intracellular lipid content, mainly by binding to adiponectin receptor, activating AMPK pathway, increasing cellular uptake of glucose and fatty acids, and promoting lipid oxidation.

SCFAs-Induced GLP-1 Secretion Links the Regulation of Gut Microbiome on Hepatic Lipogenesis in Chickens.

The impact of gut microbiota and its metabolites on fat metabolism have been widely reported in human and animals. However, the critical mediators and the signal transductions are not well demonstrated. As ovipara, chicken represents a specific case in lipid metabolism that liver is the main site of lipid synthesis. The aim of this study is to elucidate the linkage of gut microbiota and fat synthesis in broiler chickens. The broilers were subjected to dietary treatments of combined probiotics (Animal bifidobacterium: 4 × 108 cfu/kg; Lactobacillus plantarum: 2 × 108 cfu/kg; Enterococcus faecalis: 2 × 108 cfu/kg; Clostridium butyrate: 2 × 108 cfu/kg, PB) and guar gum (1 g/kg, GG), respectively. Results showed that dietary supplementation of PB and GG changed the cecal microbiota diversity, altered short chain fatty acids (SCFAs) contents, and suppressed lipogenesis. In intestinal epithelial cells (IECs), SCFAs (acetate, propionate, and butyrate) up-regulated the expression of glucagon-like peptide-1 (GLP-1) via mitogen-activated protein kinase (MAPK) pathways, mainly via the phospho - extracellular regulated protein kinase (ERK) and phospho-p38 mitogen activated protein kinase (p38 MAPK) pathways. GLP-1 suppressed lipid accumulation in primary hepatocytes with the involvement of (AMP)-activated protein kinase/Acetyl CoA carboxylase (AMPK/ACC) signaling. In conclusion, the result suggests that SCFAs-induced GLP-1 secretion via MAPK pathway, which links the regulation of gut microbiota on hepatic lipogenesis in chickens.

Excessive glucocorticoid-induced muscle MuRF1 overexpression is independent of Akt/FoXO1 pathway.

The ubiquitin-proteasome system (UPS)-dependent proteolysis plays a major role in the muscle catabolic action of glucocorticoids (GCs). Atrogin-1 and muscle-specific RING finger protein 1 (MuRF1), two E3 ubiquitin ligases, are uniquely expressed in muscle. It has been previously demonstrated that GC treatment induced MuRF1 and atrogin-1 overexpression. However, it is yet unclear whether the higher pharmacological dose of GCs induced muscle protein catabolism through MuRF1 and atrogin-1. In the present study, the role of atrogin-1 and MuRF1 in C2C12 cells protein metabolism during excessive dexamethasone (DEX) was studied. The involvement of Akt/forkhead box O1 (FoXO1) signaling pathway and the cross-talk between anabolic regulator mammalian target of rapamycin (mTOR) and catabolic regulator FoXO1 were investigated. High concentration of DEX increased MuRF1 protein level in a time-dependent fashion (P<0.05), while had no detectable effect on atrogin-1 protein (P>0.05). FoXO1/3a (Thr24/32) phosphorylation was enhanced (P<0.05), mTOR phosphorylation was suppressed (P<0.05), while Akt protein expression was not affected (P>0.05) by DEX. RU486 treatment inhibited the DEX-induced increase of FoXO1/3a phosphorylation (P<0.05) and MuRF1 protein; LY294002 (LY) did not restore the stimulative effect of DEX on the FoXO1/3a phosphorylation (P>0.05), but inhibited the activation of MuRF1 protein induced by DEX (P<0.05); rapamycin (RAPA) inhibited the stimulative effect of DEX on the FoXO1/3a phosphorylation and MuRF1 protein (P<0.05).

Corticosterone regulation of ovarian follicular development is dependent on the energy status of laying hens.

Glucocorticoids participate in the arousal of stress responses and trigger physiological adjustments that shift energy away from reproduction toward survival. Ovarian follicular development in avians is accompanied by the supply of yolk precursors, which are mainly synthesized in the liver. Therefore, we hypothesized energy status and hepatic lipogenesis are involved in the induction of reproductive disorders by glucocorticoids in laying hens. The results show that corticosterone decreased the laying performance by suppressing follicular development in energy-deficit state, rather than in energy-sufficient state. In corticosterone-treated hens, the suppressed follicular development was associated with the reduced availability of yolk precursor, indicated by the plasma concentration of VLDL and vitellogenin and the decreased proportion of yolk-targeted VLDL (VLDLy). Corticosterone decreased the expression of apolipoprotein B and apolipoprotein VLDL-II in the liver. A drop in VLDL receptor content and an increase in the expression of tight junction proteins occludin and claudin1 were also observed in hierarchical follicles. The results suggest corticosterone-suppressed follicular development is energy dependent. The decreased apolipoprotein synthesis and VLDLy secretion by liver are responsible for the decreased availability of circulating yolk precursor, and the upregulation of occludin and claudin expression further prevents yolk deposition into oocytes.

Effects of fatty acid treatments on the dexamethasone-induced intramuscular lipid accumulation in chickens.

BACKGROUND: Glucocorticoid has an important effect on lipid metabolism in muscles, and the type of fatty acid likely affects mitochondrial utilization. Therefore, we hypothesize that the different fatty acid types treatment may affect the glucocorticoid induction of intramuscular lipid accumulation. METHODOLOGY/PRINCIPAL FINDINGS: The effect of dexamethasone (DEX) on fatty acid metabolism and storage in skeletal muscle of broiler chickens (Gallus gallus domesticus) was investigated with and without fatty acid treatments. Male Arbor Acres chickens (31 d old) were treated with either palmitic acid (PA) or oleic acid (OA) for 7 days, followed by DEX administration for 3 days (35-37 d old). The DEX-induced lipid uptake and oxidation imbalance, which was estimated by increased fatty acid transport protein 1 (FATP1) expression and decreased carnitine palmitoyl transferase 1 activity, contributed to skeletal muscle lipid accumulation. More sensitive than glycolytic muscle, the oxidative muscle in DEX-treated chickens showed a decrease in the AMP to ATP ratio, a decrease in AMP-activated protein kinase (AMPK) alpha phosphorylation and its activity, as well as an increase in the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal p70S6 kinase, without Akt activation. DEX-stimulated lipid deposition was augmented by PA, but alleviated by OA, in response to pathways that were regulated differently, including AMPK, mTOR and FATP1. CONCLUSIONS: DEX-induced intramuscular lipid accumulation was aggravated by SFA but alleviated by unsaturated fatty acid. The suppressed AMPK and augmented mTOR signaling pathways were involved in glucocortcoid-mediated enhanced intramuscular fat accumulation.