Trehalose Supplementation Effects on Growth, Intestinal Morphology, Gut Bacteria, and Footpad Dermatitis of Broiler Chickens Reared at High Density.

This study aimed to measure the effects of trehalose (Tre) supplementation on the growth, intestinal morphology, gut bacteria, and footpad dermatitis (FPD) of broiler chickens reared at different stocking densities (SD). Four hundred newly hatched Ross 308 male chicks were randomly allocated to four groups of eight, following a 2 × 2 factorial arrangement in a randomized complete block design using two SDs (normal, 11; high, 14 birds/m2) and two diets: basal with and without 0.5% Tre. Tre supplementation was provided during the starter/grower phase, but not the finisher phase. Data were analyzed using a two-way analysis of variance. We observed no significant effects of SD or Tre, individually or combined, on body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) during the starter/grower period. However, high SD decreased both BWG (P < 0.001) and FI (P < 0.05), and increased FCR (P < 0.001), during the finisher period. Whereas Tre reduced FCR (P < 0.05) as a main effect, no combined effect was observed on FCR. Over the total period, high SD negatively affected BWG and FCR (P < 0.001), and Tre significantly reduced FCR, with its effect unaffected by SD. No significant effects of SD or Tre were observed on jejunal morphology. The ileal abundance of Clostridium perfringens (P > 0.05) was not affected by high SD but was significantly reduced by Tre. Neither high SD nor Tre altered Lactobacillus spp. counts; however, high SD increased FPD lesion scores, whereas Tre had no effect. The study showed that Tre supplementation during the starter/grower period improved FCR during the finisher period, possibly by decreasing the abundance of C. perfringens in broiler chickens.

Mechanisms underlying the Effects of Heat Stress on Intestinal Integrity, Inflammation, and Microbiota in Chickens.

Poultry meat and egg production benefits from a smaller carbon footprint, as well as feed and water consumption, per unit of product, than other protein sources. Therefore, maintaining a sustainable production of poultry meat is important to meet the increasing global demand for this staple. Heat stress experienced during the summer season or in tropical/subtropical areas negatively affects the productivity and health of chickens. Crucially, its impact is predicted to grow with the acceleration of global warming. Heat stress affects the physiology, metabolism, and immune response of chickens, causing electrolyte imbalance, oxidative stress, endocrine disorders, inflammation, and immunosuppression. These changes do not occur independently, pointing to a systemic mechanism. Recently, intestinal homeostasis has been identified as an important contributor to nutrient absorption and the progression of systemic inflammation. Its mechanism of action is thought to involve neuroendocrine signaling, antioxidant response, the presence of oxidants in the diet, and microbiota composition. The present review focuses on the effect of heat stress on intestinal dysfunction in chickens and the underlying causative factors. Understanding these mechanisms will direct the design of strategies to mitigate the negative effect of heat stress, while benefiting both animal health and sustainable poultry production.

Effect of Dietary 4-Phenylbuthyric Acid Supplementation on Acute Heat-Stress-Induced Hyperthermia in Broiler Chickens.

Hot, humid weather causes heat stress (HS) in broiler chickens, which can lead to high mortality. A recent study found that HS causes endoplasmic reticulum (ER) stress. However, the possible involvement of ER stress in HS-induced physiological alterations in broiler chickens is unclear. This study aimed to evaluate the effect of the dietary supplementation of 4-phenylbutyric acid (4-PBA), an alleviator of ER stress, in acute HS-exposed young broiler chickens. Twenty-eight 14-day-old male broiler chickens (ROSS 308) were divided into two groups and fed either a control diet or a diet containing 4-PBA (5.25 g per kg of diet feed) for 10 days. At 24 days old, each group of chickens was kept in thermoneutral (24 ± 0.5 °C) or acute HS (36 ± 0.5 °C) conditions for 2 h. The results showed that thermoneutral birds supplemented with 4-PBA exhibited no negative effects in terms of broiler body weight gain and tissue weight compared to non-supplemental birds. HS increased body temperature in both the control and 4-PBA groups, but the elevation was significantly lower in the 4-PBA group than in the control group. The plasma non-esterified fatty acid concentration was significantly increased by HS treatment in non-supplemental groups, while the increase was partially attenuated in the 4-PBA group. Moreover, 4-PBA prevented HS-induced gene elevation of the ER stress markers GRP78 and GRP94 in the skeletal muscle. These findings suggest that the 4-PBA effect may be specific to the skeletal muscle in HS-exposed birds and that 4-PBA supplementation attenuated HS-induced muscle ER stress, which could be associated with a supplementation of the body temperature elevation and lipolysis.

Characteristics of Essential Oils of Apiaceae Family: Their Chemical Compositions, in vitro Properties and Effects on Broiler Production.

There has been an upsurge of interest in the phytobiotics coincident with the onset of the potential ban on the use of antibiotic growth promoters (AGPs) in the broiler industry and because many kinds of nutraceuticals play an important role in improving growth performance, feed efficiency, and gut health of broilers. In the previous years, significant biological activities of essential oils (EOs) belonging to phytobiotics were observed, including anti-bacterial, antifungal, antiviral, and antioxidant properties. We found new perspectives on the roles of EOs, particularly extracts from the Apiaceae family, which is one of the largest plant families, in potential replacement of AGPs, and on the chemical composition involved in regulating microorganism activity and oxidative damage. Furthermore, the positive effects of EOs on broiler production and the possible mechanisms inducing the involvement of gut health and growth performance have been studied.

Growth performance responses to increased tryptophan supplementation in growing barrows fed three different very low crude protein corn and soybean meal-based diets fortified with essential amino acids.

Seventy-five individually fed barrows averaging 35 kg were used in a series of three experiments for 6-week growth assays (25 barrows each) to determine the effects of l-tryptophan (Trp) supplementation on growth performance and to establish the lower limits of dietary crude protein (CP) levels. Corn and soybean meal (SBM)-based diets containing 9% (Experiment 1), 10% (Experiment 2), and 11% CP (Experiment 3) fortified with deficient essential amino acids (AAs) except Trp were used as basal diets for each experiment. The experimental diets were supplemented with 0.00%, 0.02%, 0.04%, or 0.06% Trp. A 16% CP corn-SBM-based diet was set as a positive control in each experiment, and feed and water were provided ad libitum. Average daily gain and gain-to-feed ratio improved quadratically (P < 0.05) as supplemented Trp increased in the 9% and 10% CP group, although these positive effects were not observed in the 11% CP group. Because the maximum performance parameters in 9%, 10%, and 11% CP groups were not different from that of the 16% CP positive control group, the marginally reduced level of dietary CP without growth performance being affected appears to be around 9% at most. A potential reduction of nitrogen intake was clearly indicated.

Effect of dipeptide on intestinal peptide transporter 1 gene expression: An evaluation using primary cultured chicken intestinal epithelial cells.

Peptide transporter 1 (PepT1) is a transporter responsible for absorbing dipeptide and tripeptide in enterocytes and is upregulated by dipeptide in mammals. It has not been certain whether intestinal PepT1 expression is responsive to dipeptides in chickens because of the lack of in vitro study using the cultured enterocytes. This study established a primary culture model of chicken intestinal epithelial cells (IECs) in two-dimensional monolayer culture using collagen gel by which the response of chicken PepT1 gene expression to dipeptide stimuli was evaluated. The cultured chicken IECs showed the epithelial-like morphology attached in a patch-manner and exhibited positive expression of cytokeratin and epithelial cadherin, specific marker proteins of epithelial cells. Moreover, the chicken IECs exhibited the gene expression of intestinal cell type-specific marker, villin1, mucin 2, and chromogranin A, suggesting that the cultured IECs were composed of enterocytes as well as goblet and enteroendocrine cells. PepT1 gene expression was significantly upregulated by synthetic dipeptide, glycyl-l-glutamine, in the cultured IECs. From the results, we herein suggested that dipeptide is a factor upregulating PepT1 gene expression in chicken IECs.

Phytobiotics to improve health and production of broiler chickens: functions beyond the antioxidant activity.

Phytobiotics, also known as phytochemicals or phytogenics, have a wide variety of biological activities and have recently emerged as alternatives to synthetic antibiotic growth promoters. Numerous studies have reported the growth-promoting effects of phytobiotics in chickens, but their precise mechanism of action is yet to be elucidated. Phytobiotics are traditionally known for their antioxidant activity. However, extensive investigations have shown that these compounds also have anti-inflammatory, antimicrobial, and transcription-modulating effects. Phytobiotics are non-nutritive constituents, and their bioavailability is low. Nonetheless, their beneficial effects have been observed in several tissues or organs. The health benefits of the ingestion of phytobiotics are attributed to their antioxidant activity. However, several studies have revealed that not all these benefits could be explained by the antioxidant effects alone. In this review, I focused on the bioavailability of phytobiotics and the possible mechanisms underlying their overall effects on intestinal barrier functions, inflammatory status, gut microbiota, systemic inflammation, and metabolism, rather than the specific effects of each compound. I also discuss the possible mechanisms by which phytobiotics contribute to growth promotion in chickens.

In vivo emergence of beige-like fat in chickens as physiological adaptation to cold environments.

While it has been hypothesized that brown adipocytes responsible for mammalian thermogenesis are absent in birds, the existence of beige fat has yet to be studied directly. The present study tests the hypothesis that beige fat emerges in birds as a mechanism of physiological adaptation to cold environments. Subcutaneous neck adipose tissue from cold-acclimated or triiodothyronine (T3)-treated chickens exhibited increases in the expression of avian uncoupling protein (avUCP, an ortholog of mammalian UCP2 and UCP3) gene and some known mammalian beige adipocyte-specific markers. Morphological characteristics of white adipose tissues of treated chickens showed increased numbers of both small and larger clusters of multilocular fat cells within the tissues. Increases in protein levels of avUCP and mitochondrial marker protein, voltage-dependent anion channel, and immunohistochemical analysis for subcutaneous neck fat revealed the presence of potentially thermogenic mitochondria-rich cells. This is the first evidence that the capacity for thermogenesis may be acquired by differentiating adipose tissue into beige-like fat for maintaining temperature homeostasis in the subcutaneous fat 'neck warmer' in chickens exposed to a cold environment.

Effects of plant-derived isoquinoline alkaloids on growth performance and intestinal function of broiler chickens under heat stress.

Broiler chickens reared under heat stress (HS) conditions have decreased growth performance and show metabolic and immunologic alterations. This study aimed to evaluate the effect of supplementation with a standardized blend of plant-derived isoquinoline alkaloids (IQ) on the growth performance, protein catabolism, intestinal barrier function, and inflammatory status of HS-treated chickens. Three hundred sixty 0-day-old Ross 308 male broiler chickens were randomly distributed into 2 treatment groups: control diet (no additives) or diet supplemented with 100 ppm IQ. At day 14, the chicks in each diet group were further divided into 2 groups, each of which was reared under thermoneutral (TN) (22.4°C) or constant HS (33.0°C) conditions until day 42. Each group consisted of 6 replicates with 15 birds per replicate, and chickens were provided ad libitum access to water and feed. During days 15-21, the body weight gain (BWG) and feed intake (FI) were significantly lower in the HS treatment group than in the TN group, and feed conversion ratio was higher (P < 0.05); these factors were not alleviated by IQ supplementation. During days 22-42, the final BW, BWG, and FI of the HS birds were better among those administered IQ than those that were not (P < 0.05). HS treatment increased plasma lipid peroxide, corticosterone, and uric acid concentrations as well as serum fluorescein isothiocyanate-dextran, a marker of intestinal barrier function, and decreased plasma total protein content (P < 0.05). These changes were not observed in the IQ group, suggesting that IQ supplementation improved oxidative damage, protein catabolism, and intestinal barrier function of chickens under HS. Isoquinoline alkaloid supplementation inhibited the expression of intestinal inflammatory factors, IL-6, tumor necrosis factor-like factor 1A, and inducible nitric oxide synthase under HS treatment (P < 0.05). These results suggest that IQ supplementation can improve the growth performance of broiler chickens under HS conditions, which may be associated with amelioration of oxidative damage, protein catabolism, intestinal barrier function, and inflammation.

Possible role of corticosterone in proteolysis, glycolytic, and amino acid metabolism in primary cultured avian myotubes incubated at high-temperature conditions.

Excess glucocorticoid secretion induces oxidative damage and muscle proteolysis and modulates glucose and lipid metabolism. It is known that the high-temperature (HT) treatment enhances corticosterone (CORT) secretion, muscle proteolysis, and mitochondrial reactive oxygen species (mtROS) generation in chickens. The present study investigated the co-effects of CORT on proteolysis and mtROS production, together with glucose, fatty acid, and amino acid metabolism in HT-treated cells. Myoblast cells were isolated from the major pectoralis muscle of five 0- or 1-day-old neonatal chicks and were precultured at 37°C/CO2 conditions for 48 h to reach subconfluent (80%-90%) conditions. Cells were then reseeded onto a 6- or 24-well microplate for the subsequent measurement, followed by the culture under a control temperature (37°C, control) or HT (41°C) conditions for 1 or 6 h. The HT-treated cells were cocultured with physiologically relevant concentrations of CORT (20 ng/mL in dimethyl sulfoxide). The HT treatment decreased cellular protein content (P < 0.05) and increased atrogin-1 mRNA levels and mtROS generation levels compared to the control group (P < 0.05), whereas HT/CORT co-treatment did not induce changes in either parameter. The mRNA level of glucose transporter-1 was decreased in HT-treated cells compared to that in normal cells (P < 0.05), and the decrease was increased in the CORT co-treatment (P < 0.05). While HT treatment did not alter pyruvate dehydrogenase kinase-4 mRNA level, the level was increased in the CORT co-treatment compared to the control and HT-treated cells (P < 0.05). Neither HT nor HT/CORT treatments altered the mRNA levels of fatty acid oxidation-related factors, carnitine palmitoyl transferase-1, and cluster of differentiation 36. The study conducted a metabolic analysis using gas chromatography-mass spectrometry. The results showed that HT/CORT-treated cells had decreased intracellular citrate and α-ketoglutarate levels (P < 0.05) and increased extracellular alanine and amino acid that have gluconeogenic properties, as well as increased aspartate, isoleucine, serine, methionine, and threonine levels (P < 0.05) compared to HT-treated cells. These results suggest that CORT may not affect proteolysis and mtROS production but can suppress pyruvate oxidation and promote alanine production in HT-treated chickens.

Oleuropein suppresses mitochondrial reactive oxygen species generation possibly via an activation of transient receptor potential V1 and sirtuin-1 in cultured chicken muscle cells.

This study investigated the intracellular mechanism governing the effects of oleuropein (OLE), a phenolic compound of Olea europaea, on mRNA expression of avian uncoupling protein (avUCP) and mitochondrial biogenesis-related factors, and reactive oxygen species (mitROS) generation in a primary cultured chicken muscle cells. The OLE-treated cells exhibited increases in Avucp and ATP5a1z expression and a decrease in mitROS generation (p < 0.05), while the effects was canceled by sirtuin-1 (SIRT1) or transient receptor potential vanilloid 1 (TRPV1) inhibitors, EX-527 or BCTC, respectively. Intracellular Ca2+ concentration was significantly increased by OLE, while the induction was canceled by BCTC. The study also found that TRPV1 was expressed in the cell membrane and endoplasmic reticulum (ER), and Ca2+ could be released from ER in the OLE-treated cells. The OLE-treated cells exhibited increases in the phosphorylation ratio of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein content. EX-527 and BCTC inhibitors canceled the effects of OLE on p-AMPK ratio and PGC-1α content, while EX-527 SIRT did not change PGC-1α content. The results suggest that the OLE effects may be due to Ca2+ release, possibly from TRPV1 at ER, and increased p-AMPK ratio, followed by SIRT1 activation and PGC-1α protein expression.

Heat Stress Directly Affects Intestinal Integrity in Broiler Chickens.

A study using pair-feeding technique was conducted to determine whether heat exposure directly or indirectly (via reduced feed intake) increases intestinal mucosal damage and permeability to endotoxin in broiler chickens. Male broiler chickens (Ross 308), 27-d-old, were subjected to one of the three treatments (n=8): 1) thermo-neutral conditions (24°C) with ad libitum feed intake, 2) heat stress conditions (33°C) with ad libitum feed intake, or 3) pair-feeding under thermo-neutral conditions, with the feed intake identical to that of heat-stressed chickens. Using these groups, two experiments were performed to evaluate temporal changes in the intestinal morphology in response to each treatment. In experiment 1, chickens were sacrificed after 24 h of exposure to the treatment conditions, while in experiment 2, chickens were sacrificed after 12 or 72 h of exposure to the treatment conditions. In experiment 1, exposure to heat stress conditions for 24 h significantly decreased both the villus height to crypt depth ratio and number of proliferating cell nuclear antigen (PCNA)-positive cells in the duodenum and increased the plasma endotoxin concentration. These findings were not observed in pair-fed chickens. In experiment 2, intestinal integrity and function were unaffected by 12 h of heat stress. On the other hand, chickens exposed to heat stress for 72 h exhibited significantly damaged intestinal morphology in the duodenum as well as increased plasma endotoxin concentration; these negative effects were not observed in pair-fed chickens. These findings suggest that the intestinal morphology and permeability changes observed in chickens that are heat-stressed for 24-72 h are due to the heat stress conditions and not due to reduced feed intake.

Differences in Breast Muscle Mitochondrial Respiratory Capacity, Reactive Oxygen Species Generation, and Complex Characteristics between 7-week-old Meat- and Laying-type Chickens.

The skeletal muscle growth rate is a major feature differentiating meat- and laying-type chickens. A large amount of ATP is required during skeletal muscle synthesis, in which mitochondrial energy production capacities play a significant role. Additionally, mitochondria may participate in muscle protein degradation via reactive oxygen species generation. To investigate the differences in mitochondrial energetic characteristics between chickens exhibiting different growth rates, this study evaluated respiratory capacities in response to different types of respiratory substrate, protein abundances, assembly of individual respiratory complexes (I-V) and supercomplexes, and reactive oxygen species generation rates. These characteristics were compared between mitochondria from the breast muscle (M. pectoralis superficialis) of seven-week-old meat- and laying-type male chickens. Blue native polyacrylamide gel electrophoresis analysis revealed that meat-type chickens exhibited a significantly lower protein abundance of complex III (cytochrome bc 1 complex), complex V (F0F1 ATP synthase), and total amount of supercomplexes than did laying-type chickens. There were no differences between chicken types in the respiration rate of mitochondria incubated with either pyruvate/malate or succinate, each of which drives complex I- and complex II-linked respiration. Carnitine palmitoyltransferase-1-dependent and -independent respiration during ATP synthesis and carnitine palmitoyltransferase-2 enzymatic activity were significantly lower in meat-type chickens than in layingtype chickens. For mitochondria receiving pyruvate/malate plus succinate, the reactive oxygen species generation rate and its ratio to the oxygen consumed (the percentage of free radical leak) were also significantly lower in meat-type chickens than in laying-type chickens. These results suggested that the mitochondrial energetic capacities of the breast muscle of meat-type chickens could be lower than those of laying-type chickens at seven weeks of age. Furthermore, the lower reactive oxygen species generation rate in meat-type chickens might have implications for rapid muscle development, which is possibly related to their lower muscle protein degradation rates.

Effect of trehalose supplementation on growth performance and intestinal morphology in broiler chickens.

Trehalose (Tre) is a natural disaccharide. A laboratory-scale investigation showed that Tre supplementation increased the growth rate in juvenile chicks, possibly via the improvement of innate intestinal immune responses. In this study, two trials were conducted to evaluate the growth-promoting effect of Tre supplementation in broiler chickens. In experiment-1, two thousand day-old male and female broiler chicks (Ross) were fed 0 (control), 0.25, 0.50, and 0.75% Tre-supplemented pellet-form diets from d 1-17, and subsequently, they were provided grower (d 18-30) and finisher (d 31-37) diets without Tre supplementation. Over the trial period, there was no significant difference in body weight (BW), feed intake and feed conversion ratio (FCR) between chickens in the control and Tre-fed groups. Tre treatment increased villus height (VH)/crypt depth (CD) ratio and villus surface in jejunum; decreased CD and increased VH/CD ratio in ileum on d 17, when these results were compared to the control group. In experiment-2, two hundred day-old female broiler chicks were fed an antibiotics-free and mash-form diet supplemented with 0.5% Tre from d 1-21, before being fed a non-supplemental diet until d 43. There was no difference in BW on d 21 between the control and Tre-0.5% groups; however, from d 22-43, Tre-0.5% group showed significantly higher BW gain and lower FCR compared to the control group. From these results, we suggest that Tre feeding can be beneficial for intestinal morphology and growth performance in broiler chickens. However, these outcomes did not occur in parallel owing to the different feeding conditions observed.

Variation in lysine, threonine, and tryptophan availability in meat and bone meal as estimated by the slope-ratio growth assay technique in growing rats.

Meat and bone meal (MBM) is an important protein source used in animal feeds. However, as the composition and availability of amino acids (AAs) in MBM fluctuate markedly, it is important to verify the magnitude of these parameters in different MBMs. In this study, the AA compositions of 19 MBMs were analyzed to confirm variations in lysine (Lys), threonine (Thr), and tryptophan (Trp), then which were compared with those of soybean meal (SBM) and fish meal (FM). Instability in Lys, Thr, and Trp availabilities in six MBMs were also considered after estimation using the slope-ratio growth assay technique in rats. Variations in AA composition were evaluated using the coefficient of variance (CV: Standard deviation/Mean). CVs for Lys, Thr, and Trp content were 9.40, 11.83, and 18.12 in MBM, 2.71, 2.48, and 3.19 in SBM, and 10.09, 10.44, and 13.47 in FM. Furthermore, means and SDs for Lys, Thr, and Trp availabilities in MBM were 53.3 ± 10.4% (CV: 19.5), 65.9 ± 17.6% (CV: 26.6), and 83.2 ± 11.2% (CV: 13.5), respectively. These results provide the first evidence that variations in MBM AA compositions were 3.5 to 5.7 times higher than those in SBM, but similar to FM, and that the large variation in availability substantially existed.

Heat Stress Causes Immune Abnormalities via Massive Damage to Effect Proliferation and Differentiation of Lymphocytes in Broiler Chickens.

Broiler chickens are highly sensitive to high ambient temperatures due to their feathers, lack of skin sweat glands, and high productivity. Heat stress (HS) is a major concern for the poultry industry because it negatively affects growth as well as immune functions, which increase the potential risk of infectious disease outbreaks. Therefore, it is vital to elucidate HS's effect on the avian immune system, especially considering the global rise in average surface temperature. Our study identified a series of immunological disorders in heat-stressed broiler chickens. We exposed 22-day-old broiler chickens to a continuous HS condition (34.5 ± 0.5°C) for 14 days and immunized them with a prototype bovine serum albumin (BSA) antigen. The plasma and lymphoid tissues (thymus, bursa of Fabricius, and spleen) were harvested at the end of the experiments to investigate the induction of BSA-specific immune responses. Our results revealed that plasma titers of immunoglobulin (Ig)Y, IgM, and IgA antibodies specific for BSA were lower than those of thermoneutral chickens immunized with BSA. Furthermore, the spleens of the heat-stressed broiler chickens displayed severe depression of Bu1+ B cells and CD3+ T cells, including CD4+ T cells and CD8+ T cells, and lacked a fully developed germinal center (GC), which is crucial for B cell proliferation. These immunological abnormalities might be associated with severe depression of CD4-CD8- or CD4+CD8+ cells, which are precursors of either helper or killer T cells in the thymus and Bu1+ B cells in the bursa of Fabricius. Importantly, HS severely damaged the morphology of the thymic cortex and bursal follicles, where functional maturation of T and B cells occur. These results indicate that HS causes multiple immune abnormalities in broiler chickens by impairing the developmental process and functional maturation of T and B cells in both primary and secondary lymphoid tissues.

Correlations between mitochondrial respiration activity and residual feed intake after divergent genetic selection for high- and low- oxygen consumption in mice.

The aims of the present study were to identify the differences between two mouse lines (high (H)- and low (L)-oxygen consumption) in terms of mitochondrial respiratory activity when GMP (glutamate, malate, and pyruvate) and succinic acid are used as substrates and to examine the relationship between mitochondrial respiration activity and feed efficiency in both lines. The average daily feed intake, feed conversion ratio (FCR), and residual feed intake (RFI) were significantly higher in the H than the L line. The correlation between FCR and RFI was significant (r = 0.60, p < 0.05). RFI was effective as an indicator of feed efficiency. When succinic acid was used as a substrate, mitochondrial respiration states 2-4, ACR, and proton leak were significantly higher in the H than the L line. When GMP was used as a substrate, respiration states 3 and 4 in the H line were significantly higher than those in the L line, and there were significant positive correlations between FCR and RFI and mitochondrial respiration states 2-4. The results indicated that selection for high or low OC changed the basal metabolic rates estimated from liver mitochondrial respiration activity and feed efficiency.

Characterization of Mitochondrial Content and Respiratory Capacities of Broiler Chicken Skeletal Muscles with Different Muscle Fiber Compositions.

Mitochondrial content is regarded a useful feature to distinguish muscle-fiber types in terms of energy metabolism in skeletal muscles. Increasing evidence suggests that specific mitochondrial bioenergetic phenotypes exist in metabolically different muscle fibers. A few studies have examined the energetic properties of skeletal muscle in domestic fowls; however, no information on muscle bioenergetics in broiler chickens selectively bred for faster growth is available. In this study, we aimed to characterize the mitochondrial contents and functions of chicken skeletal muscle consisting entirely of type I (oxidative) (M. pubo-ischio-femoralis pars medialis), type IIA (glycolytic/oxidative) (M. pubo-ischio-femoralis pars lateralis), and type IIB (glycolytic) (M. pectoralis) muscle fibers. Citrate synthase (CS) activity was the highest in type IIA muscle tissues and isolated mitochondria, among the muscle tissues tested. Although no difference was registered in mitochondrial CS activity between type IIB and type I muscles, tissue CS activity was significantly higher in the latter. Histochemical staining for NADH tetrazolium reductase and the ratio of muscle-tissue to mitochondrial CS activity indicated that type I, type IIA, and type IIB muscle-fiber types showed decreasing mitochondrial content. Mitochondria from type I muscle exhibited a higher coupled respiration rate induced by pyruvate/malate, palmitoyl-CoA/malate, and palmitoyl-carnitine, as respiratory substrates, than type IIB-muscle mitochondria, while the response of mitochondria from type IIA muscle to those substrates was comparable to that of mitochondria from type I muscle. Type IIA-muscle mitochondria exhibited the highest carnitine palmitoyltransferase-2 level among all tissues tested, which may contribute to the higher fatty acid oxidation in these mitochondria. The results suggest that mitochondrial abundance is one of the features differentiating metabolic characteristics of different chicken skeletal muscle types. Moreover, the study demonstrated that type IIA-muscle mitochondria may have distinct metabolic capacities.

Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases.

Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model "Mitomouse" (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial.

Selection for high and low oxygen consumption-induced differences in maintenance energy requirements of mice.

Maintenance energy requirements (MER) of mice selected for high (H) or low (L) oxygen consumption (OC) were compared. Forty-four mice from H and L OC lines were weaned at 3 weeks and divided into four experimental groups: group A were sacrificed at 4 weeks; group B were fed ad libitum, and groups C and D were fed 2.8 and 2.4 g/day, respectively, from 4 to 8 weeks of age. Groups B-D were sacrificed at 8 weeks. Chemical components were estimated for all groups. MER was estimated using a model that partitioned metabolizable energy intake into that used for maintenance, and protein and fat deposition. The feed conversion ratio for the B group was significantly higher in the H than in the L line. Feed intake for metabolic energy content per metabolic body size was significantly also higher in the H line, whereas accumulated energy content per metabolic body size was significantly higher in the L line. MER of the H line was greater than that of the L line (P < 0.10). These results suggest that selection for H or L OC produced differences in chemical components, feed efficiency, and MER between the H and L lines.