Dynamic transcriptome profiles of skeletal muscle growth and development in Shaziling and Yorkshire pigs using RNA-sequencing.

BACKGROUND: We previously demonstrated that Shaziling and Yorkshire pigs differ in growth rate and meat quality. However, the molecular mechanisms responsible for such phenotypic differences remain unclear. In the present study, we performed a transcriptomic analysis of 36 longissimus dorsi (LM) and 36 soleus (SM) muscle samples from Shaziling and Yorkshire pigs at six postnatal stages (30, 60, 90, 150, 210 and 300 days) to explore the differences in postnatal skeletal muscle of Shaziling and Yorkshire pigs. RESULTS: Muscle morphological changes and the number of differentially expressed genes indicated the two stages of 60-90 days and 150-210 days were critical for the muscle growth and development in Shaziling pigs. Genes such as FLNC, COL1A1, NRAP, SMYD1, TNNI3, CRYAB and PDLIM3 played vital roles in the muscle growth, and genes such as CCDC71L, LPIN1, CPT1A, UCP3, NR4A3 and PDK4 played dominant roles in the lipid metabolism. Additionally, in contrast to the LM, the percentage of slow-twitch muscle fibers in the SM of both breeds consistently decreased from 30 to 150 days of age, but there was a significant rebound at 210 days of age. However, the percentage of slow-twitch muscle fibers in the SM of Shaziling pigs was higher than that in Yorkshire pigs, which may be associated with the calcium signaling pathway and the PPARß/δ signaling pathway. CONCLUSION: The present study detected two critical periods and many functional genes for the muscle growth and development of Shaziling pigs, and showed differences in muscle fiber characteristics between Shaziling and Yorkshire pigs. © 2024 Society of Chemical Industry.

Characterisation of forkhead box protein A3 as a key transcription factor for hepatocyte regeneration.

Background & Aims: Liver regeneration is vital for the recovery of liver function after injury, yet the underlying mechanism remains to be elucidated. Forkhead box protein A3 (FOXA3), a member of the forkhead box family, plays important roles in endoplasmic reticulum stress sensing, and lipid and glucose homoeostasis, yet its functions in liver regeneration are unknown. Methods: Here, we explored whether Foxa3 regulates liver regeneration via acute and chronic liver injury mice models. We further characterised the molecular mechanism by chromatin immunoprecipitation sequencing and rescue experiments in vivo and in vitro. Then, we assessed the impact of Foxa3 pharmacological activation on progression and termination of liver regeneration. Finally, we confirmed the Foxa3-Cebpb axis in human liver samples. Results: Foxa3 is dominantly expressed in hepatocytes and cholangiocytes and is induced upon partial hepatectomy (PH) or carbon tetrachloride (CCl4) administration. Foxa3 deficiency in mice decreased cyclin gene levels and delayed liver regeneration after PH, or acute or chronic i.p. CCl4 injection. Conversely, hepatocyte-specific Foxa3 overexpression accelerated hepatocytes proliferation and attenuated liver damage in an CCl4-induced acute model. Mechanistically, Foxa3 directly regulates Cebpb transcription, which is involved in hepatocyte division and apoptosis both in vivo and in vitro. Of note, Cebpb overexpression in livers of Foxa3-deficient mice rescued their defects in cell proliferation and regeneration upon CCl4 treatment. In addition, pharmacological induction of Foxa3 via cardamonin speeded up hepatocyte proliferation after PH, without interfering with liver regeneration termination. Finally, Cebpb and Ki67 levels had a positive correlation with Foxa3 expression in human chronic disease livers. Conclusions: These data characterise Foxa3 as a vital regulator of liver regeneration, which may represent an essential factor to maintain liver mass after liver injury by governing Cebpb transcription. Impact and Implications: Liver regeneration is vital for the recovery of liver function after chemical insults or hepatectomy, yet the underlying mechanism remains to be elucidated. Herein, via in vitro and in vivo models and analysis, we demonstrated that Forkhead box protein A3 (FOXA3), a Forkhead box family member, maintained normal liver regeneration progression by governing Cebpb transcription and proposed cardamonin as a lead compound to induce Foxa3 and accelerate liver repair, which signified that FOXA3 may be a potential therapeutic target for further preclinical study on treating liver injury.

HnRNPA2B1 Aggravates Inflammation by Promoting M1 Macrophage Polarization.

Macrophages have critical contributions to both acute and chronic inflammatory diseases, for example, bowel disease and obesity, respectively. However, little is known about the post-transcriptional regulatory mechanisms in macrophage-mediated inflammatory diseases. hnRNPA2B1 (A2B1) is an RNA binding protein for mRNA fate determination. We showed that hnRNPA2B1 mRNA levels were increased in colon in dextran sodium sulfate (DSS)-induced colitis mice and in epididymal white adipose tissue (eWAT) and spleen of high-fat-diet (HFD)-induced obese mice. Consistently, mice with haploinsufficiency of A2B1 (A2B1 HET) are protected against DSS-induced acute colitis and HFD-induced obesity, with decreased M1 macrophages polarization in colon, eWAT and spleen. Mechanistically, A2B1 mRNA and protein levels were increased in LPS-stimulated RAW 264.7 macrophages, and A2B1 enhanced RNA stability of pro-inflammatory genes Tnfα, Il-6 and Il-1ß for the regulation of macrophages polarization. Interestingly, A2B1 HET mice exhibited reduced white fat expansion, which was influenced by macrophages, since conditioned medium from macrophages with A2B1 manipulation significantly changed preadipocyte proliferation. Our data demonstrate that A2B1 plays a vital role in macrophage-mediated inflammation via regulating mRNA stability, suggesting that A2B1 may be served as a promising target for the intervention of acute and chronic inflammatory diseases.

Profiles of muscular amino acids, fatty acids, and metabolites in Shaziling pigs of different ages and relation to meat quality.

Pork meat is closely related to physicochemical alterations during growth and development, resulting in differences in nutritional value and meat flavor. This study aimed to evaluate the composition of amino acids, fatty acids, and metabolic profiles in the longissimus thoracis muscle (LM) of Shaziling pigs aged 30, 90, 150, 210, and 300 days. The results showed that the predominant fatty acids identified in the LM of Shaziling pigs were C16:0, C16:1, C18:0, C18:1n9c, and C18:2n6c. An opposite correlation was observed for C18:2n6c and n6/n3 polyunsaturated fatty acids (P<0.05). Alanine, aspartate, glutamate, D-glutamine, and D-glutamate metabolism were the main metabolic pathways for the Shaziling pig meat flavor (P<0.05). Moreover, the correlation coefficients revealed that the contents of anserine, C16:0, C16:1, and C18:1n9c were positively correlated with intramuscular fat and/or pH24h and were negatively correlated with the values of L* (lightness) and b* (yellowness) (P<0.05). In conclusion, age greatly affected the meat quality of Shaziling pigs, and the contents of muscular anserine, C16:0, C16:1, and C18:1n9c might be promising indicators for better meat quality.

Irisin ameliorates age-associated sarcopenia and metabolic dysfunction.

BACKGROUND: Age-associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age-associated sarcopenia and metabolic dysfunction. METHODS: The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2- and 24-month-old mice or human subjects were analysed using qRT-PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14-month-old) for 4 months or in aged mice (22-month-old) for 1 month to systematically investigate irisin's effects on age-associated sarcopenia and metabolic performances, including grip strength, body weights, body composition, insulin sensitivity, energy expenditure, serum parameters and phenotypical and molecular changes in fat and liver. RESULTS: We showed that the expression levels of irisin, as well as its precursor Fndc5, were reduced at mRNA and protein expression levels in muscle during ageing. In addition, via phenotypic analysis of FNDC5/irisin knockout mice, we found that FNDC5/irisin deficiency in aged mice exhibited aggravated muscle atrophy including smaller grip strength (-3.23%, P < 0.05), muscle weights (quadriceps femoris [QU]: -20.05%; gastrocnemius [GAS]: -17.91%; tibialis anterior [TA]: -19.51%, all P < 0.05), fibre size (QU: P < 0.01) and worse molecular phenotypes compared with wild-type mice. We then delivered recombinant irisin protein intraperitoneally into ageing or aged mice and found that it could improve sarcopenia with grip strength (+18.42%, P < 0.01 or +13.88%, P < 0.01), muscle weights (QU: +9.02%, P < 0.01 or +16.39%, P < 0.05), fibre size (QU: both P < 0.05) and molecular phenotypes and alleviated age-associated fat tissues expansion, insulin resistance and hepatic steatosis (all P < 0.05), accompanied with altered gene signatures. CONCLUSIONS: Together, this study revealed the importance of irisin in the maintenance of muscle physiology and systematic energy homeostasis during ageing and suggested a potent therapeutic strategy against age-associated metabolic diseases via irisin administration.

Dietary Beta-Hydroxy-Beta-Methyl Butyrate Supplementation Inhibits Hepatic Fat Deposition via Regulating Gut Microbiota in Broiler Chickens.

The present study is aimed to explore the effects of different dietary beta-hydroxy-beta-methyl butyrate (HMB) levels (0, 0.05%, 0.10%, or 0.15%) on liver lipid metabolism on Wenshi broiler chickens. Results showed that HMB reduced the liver weight as well as liver concentrations of triacylglycerol (TG) and total cholesterol (TC) (quadratically, p < 0.05), and the lowest values were observed in the 0.10% HMB group. Meanwhile, HMB supplementation significantly altered the expression levels of key genes related to lipid metabolism in the liver of broiler chickens (p < 0.05). Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation could greatly change the richness, diversity, and composition of the broiler gut microbiota, and the Bacteroidetes relative abundance at the phylum level and the Alistipes relative abundance at the genus level were affected (p < 0.05). Correlation analysis further suggested a strong association between Bacteroidetes relative abundance and lipid metabolism-related parameters (p < 0.05). Together, these data suggest that 0.10% HMB supplementation could inhibit hepatic fat deposition via regulating gut microbiota in broilers.

Comparisons of carcass traits, meat quality, and serum metabolome between Shaziling and Yorkshire pigs.

This study aims to compare the meat quality of Shaziling and Yorkshire pigs and to find the potential indicator in serum for superior meat quality. Six Shaziling and Yorkshire pigs at 30, 60, 90, 150, 210, and 300 d of age were selected to examine carcass traits, meat quality, and serum metabolome. The results showed that the body weight, carcass length, and loin eye area of Shaziling pigs at 150, 210, and 300 d of age were significantly lower than those of Yorkshire pigs (P < 0.05). Shaziling pigs at 150 and 300 d of age had significantly lower backfat thickness than Yorkshire pigs (P < 0.05). Compared with Yorkshire pigs, Shaziling pigs at all 6 ages had a lower lean percentage and a higher fat percentage (P < 0.05). At 60, 90, and 150 d of age, the post-mortem pH-decline, b∗ value (yellowness), and drip loss of Shaziling pigs were significantly lower than those of Yorkshire pigs (P < 0.05). Moreover, at 150 d of age, Shaziling pigs had significantly higher a∗ value (redness) and intramuscular fat (IMF) content than Yorkshire pigs (P < 0.05). Correlation analysis between the top 40 metabolites and phenotypes indicated that L-carnitine had positive correlations with fat percentage, pH24h, and IMF content, but had negative correlations with lean percentage, L∗ value (lightness), and b∗ value (P < 0.05). Serum L-carnitine content, fat percentage, pH24h, and IMF content all decreased first and then increased as the pigs grew, which verified the positive correlations between L-carnitine and these phenotypes. In conclusion, Shaziling pigs have a slower growth rate but a better meat quality than Yorkshire pigs. The meat quality of Shaziling pigs is the best from 150 to 210 d of age. This study suggests that a higher serum L-carnitine content is a promising indicator for better meat quality.

Effects of Dietary Tea Powder on the Growth Performance, Carcass Traits, and Meat Quality of Tibetan Pig × Bama Miniature Pigs.

This study was conducted to evaluate the effects of tea powder in diets on the growth performance, meat quality, muscular amino acid, fatty acid profile, and serum biochemical indices of pigs. A total of 120 local Chinese pigs (Tibetan × Bama miniature pigs) were randomly assigned to five treatment groups, each with six pens and four pigs per pen. During a 60-day experiment, these groups of pigs were fed the normal diet and the diet supplemented with 1%, 2%, 4%, and 6% tea powder, respectively. The results showed that the supplementation of tea powder did not affect the growth performance of pigs. However, the dietary tea powder inclusion decreased (p < 0.05) the average fat thickness, total fat, and abdominal fat, and increased (p < 0.05) the total muscle as well. In addition, the dietary 2% tea powder decreased (p < 0.05) the muscle lightness (L*) and yellowness (b*). Compared with the control group, the dietary supplementation with 1%, 2%, and 4% tea powder raised (p < 0.05) the total amino acids (TAA) and essential amino acids (EAA), and dietary 4% and 6% tea powder increased (p < 0.05) the C20:5n3 in the muscle tissue. Furthermore, the serum lipid metabolism-related biochemical indices and mRNA expression levels were improved with the addition of tea powder. These results indicated that dietary tea powder might improve the carcass traits and meat quality of the Chinese native finishing pigs, but it does not affect their growth performance. Tea powder could be fully developed and reasonably applied as a dietary supplement.

Plant Extracts in Obesity: A Role of Gut Microbiota.

Obesity has become one of the most serious chronic diseases threatening human health. Its occurrence and development are closely associated with gut microbiota since the disorders of gut microbiota can promote endotoxin production and induce inflammatory response. Recently, numerous plant extracts have been proven to mitigate lipid dysmetabolism and obesity syndrome by regulating the abundance and composition of gut microbiota. In this review, we summarize the potential roles of different plant extracts including mulberry leaf extract, policosanol, cortex moutan, green tea, honokiol, and capsaicin in regulating obesity via gut microbiota. Based on the current findings, plant extracts may be promising agents for the prevention and treatment of obesity and its related metabolic diseases, and the mechanisms might be associated with gut microbiota.

HMB Improves Lipid Metabolism of Bama Xiang Mini-Pigs via Modulating the Bacteroidetes-Acetic Acid-AMPKα Axis.

Here, we used Bama Xiang mini-pigs to explore the effects of different dietary ß-hydroxy-ß-methylbutyrate (HMB) levels (0, 0.13, 0.64 or 1.28%) on lipid metabolism of adipose tissue. Results showed that HMB decreased the fat percentage of pigs (linearly, P < 0.05), and the lowest value was observed in the 0.13% HMB group. Moreover, the colonic acetic acid concentration and the relative Bacteroidetes abundance were increased in response to HMB supplementation (P < 0.05). Correlation analysis identified a positive correlation between the relative Bacteroidetes abundance and acetic acid production, and a negative correlation between fat percentage and the relative Bacteroidetes abundance or acetic acid production. HMB also upregulated the phosphorylation (p) of AMPKα, Sirt1, and FoxO1, and downregulated the p-mTOR expression. Collectively, these findings indicate that reduced fat percentage in Bama Xiang mini-pigs could be induced by HMB supplementation and the mechanism might be associated with the Bacteroidetes-acetic acid-AMPKα axis.

Dietary supplementation with betaine or glycine improves the carcass trait, meat quality and lipid metabolism of finishing mini-pigs.

The objective of the study is to evaluate and compare the effects of betaine or glycine on carcass trait, meat quality and lipid metabolism of finishing Huan Jiang mini-pigs. Betaine called trimethylglycine is a methyl derivative of glycine, but few researches were conducted to compare the impact of dietary betaine and glycine on pigs. One hundred and forty-four Huan Jiang mini-pigs (body weight = 10.55 ± 0.15 kg; 70 d) were randomly divided to 3 treatment groups (basal diet, glycine or betaine). Results indicated that dietary betaine increased the average daily gain (ADG) and final weight (P < 0.05). Dietary glycine or betaine markedly reduced average backfat thickness (P < 0.05) and heightened lean percentage (P < 0.01) compared to the control group. Moreover, in comparison with the control group, betaine significantly improved the redness (a∗) and tenderness (shear force) of the longissimus dorsi (LD) muscle (P < 0.05), whereas glycine only raised the value of a∗ of the LD muscle (P < 0.05). These results showed that diet supplemented with 0.25% betaine and equimolar amounts of glycine could regulate cascass trait and meat quality of finishing Huan Jiang mini-pigs, and the effect of betaine was superior to that of glycine.

Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets.

The current study was performed to investigate whether dietary ß-hydroxy-ß-methylbutyrate (HMB) could regulate liver injury in a lipopolysaccharide- (LPS-) challenged piglet model and to determine the mechanisms involved. Thirty piglets (21 ± 2 days old, 5.86 ± 0.18 kg body weight) were randomly divided into the control (a basal diet, saline injection), LPS (a basal diet), or LPS+HMB (a basal diet + 0.60% HMB-Ca) group. After 15 d of treatment with LPS and/or HMB, blood and liver samples were obtained. The results showed that in LPS-injected piglets, HMB supplementation ameliorated liver histomorphological abnormalities induced by LPS challenge. Compared to the control group, the activities of serum aspartate aminotransferase and alkaline phosphatase were increased in the LPS-injected piglets (P < 0.05). The LPS challenge also downregulated the mRNA expression of L-PFK, ACO, L-CPT-1, ICDH ß, and AMPKα1/2 and upregulated the mRNA expression of PCNA, caspase 3, TNF-α, TLR4, MyD88, NOD1, and NF-κB p65 (P < 0.05). However, these adverse effects of the LPS challenge were reversed by HMB supplementation (P < 0.05). These results indicate that HMB may exert protective effects against LPS-induced liver injury, and the underlying mechanisms might involve the improvement of hepatic energy metabolism via regulating AMPK signaling pathway and the reduction of liver inflammation via modulating TLR4 and NOD signaling pathways.

Flavonoids from Mulberry Leaves Alleviate Lipid Dysmetabolism in High Fat Diet-Fed Mice: Involvement of Gut Microbiota.

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for six weeks. FML administration improved lipid accumulation, alleviated liver steatosis and the whitening of brown adipose tissue, and improved gut microbiota composition in HFD-fed mice. Microbiota transplantation from FML-treated mice alleviated HFD-induced lipid metabolic disorders. Moreover, FML administration restored the production of acetic acid in HFD-fed mice. Correlation analysis identified a significant correlation between the relative abundances of Bacteroidetes and the production of acetic acid, and between the production of acetic acid and the weight of selected adipose tissues. Overall, our results demonstrated that in HFD-fed mice, the lipid metabolism improvement induced by FML administration might be mediated by gut microbiota, especially Bacteroidetes-triggered acetic acid production.

Antioxidant mechanism of tea polyphenols and its impact on health benefits.

Tea trees have a long history of cultivation and utilization. People in many countries have the habit of drinking tea and choosing green tea, oolong tea, or black tea according to different regions and personal tastes. Tea polyphenols are a general term for polyphenol compounds in tea, and has been shown to have good effects on antioxidant, anti-inflammatory, cancer prevention and regulation of lipid metabolism. Tea polyphenols have been widely used as antioxidants in disease treatment and animal husbandry, but their specific mechanism of action needs to be further clarified and revealed. This review focuses on the definition, classification, antioxidant activity and the regulation of signaling pathways of tea polyphenols. This paper also aims to examine the application of tea polyphenols in human and animal health, providing a scientific basis for this application in addition to proposing future directions for the development of this resource.

Dietary ß-hydroxy-ß-methylbutyrate improves intestinal function in weaned piglets after lipopolysaccharide challenge.

OBJECTIVES: The aim of this study was to explore the effects of ß-hydroxy-ß-methylbutyrate (HMB) on intestinal function of lipopolysaccharide (LPS)-challenged piglets. METHODS: Forty weaned piglets were used in a 2 × 2 factorial design. The major factors were challenge (saline or LPS) and diet (basal diet or 0.6% HMB-Ca diet). After 15 d of treatment with LPS or HMB, blood and intestine samples were obtained. RESULTS: The results showed that in LPS-injected pigs, HMB supplementation significantly increased jejunal villus height and ileal villus height-to-crypt depth ratio and decreased ileal crypt depth (P < 0.05). HMB also improved intestinal function indicated by elevated activities of intestinal mucosal disaccharidase and tricarboxylic acid cycle key enzymes. Furthermore, HMB significantly downregulated mRNA expression of Sirt1 in jejunum and mRNA expression of AMPKα1 and Sirt1 in ileum (P < 0.05), with a concurrent decrease of AMPKα phosphorylation in jejunum and ileum. Microbiota analysis indicated that HMB supplementation significantly increased α-diversity and affected relative abundances of Romboutsia and Sarcina at the genus level, accompanied by increased concentrations of all short-chain fatty acids except propionate in the terminate ileum of LPS-injected piglets. CONCLUSION: Dietary HMB supplementation could improve intestinal integrity, function, microbiota communities, and short-chain fatty acid concentrations in LPS-challenged piglets, suggesting its potential usage as a feed additive in weaned piglets to alleviate intestinal dysfunction triggered by immune stress.

Leucine Supplementation: A Novel Strategy for Modulating Lipid Metabolism and Energy Homeostasis.

Lipid metabolism is an important and complex biochemical process involved in the storage of energy and maintenance of normal biological functions. Leucine, a branched amino acid, has anti-obesity effects on glucose tolerance, lipid metabolism, and insulin sensitivity. Leucine also modulates mitochondrial dysfunction, representing a new strategy to target aging, neurodegenerative disease, obesity, diabetes, and cardiovascular disease. Although various studies have been carried out, much uncertainty still exists and further studies are required to fully elucidate the relationship between leucine and lipid metabolism. This review offers an up-to-date report on leucine, as key roles in both lipid metabolism and energy homeostasis in vivo and in vitro by acceleration of fatty acid oxidation, lipolysis, activation of the adenosine 5'-monophosphate-activated protein kinase (AMPK)-silent information regulator of transcription 1 (SIRT1)-proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, synthesis, and/or secretion of adipokines and stability of the gut microbiota.

Suppression of protein degradation by leucine requires its conversion to ß-hydroxy-ß-methyl butyrate in C2C12 myotubes.

The aims of this study were to investigate whether the inhibitory effect of Leucine (Leu) on starvation-induced protein degradation was mediated by its metabolite ß-hydroxy-ß-methyl butyrate (HMB), and to explore the mechanisms involved. The results showed that the beneficial effects of Leu on protein degradation and the oxygen consumption rate (OCR) of cells were observed at low levels (0.5 mM) rather than at high levels (10 mM). However, these effects were inferior to those of HMB. Moreover, HMB was able to increase/decrease the proportion of MyHC I/MyHC IIb protein expression, respectively. In these KICD-transfected cells, Leu was approximately as effective as HMB in inhibiting protein degradation and increasing the OCR as well as MyHC I protein expression of cells, and these effects of Leu were reverted to a normal state by mesotrione, a specific suppressor of KICD. In conclusion, HMB seems to be an active metabolite of Leu to suppress muscle protein degradation in a starvation model, and the mechanisms may be associated with improved mitochondrial oxidative capacity in muscle cells.

Beta-hydroxy beta-methyl butyrate decreases muscle protein degradation via increased Akt/FoxO3a signaling and mitochondrial biogenesis in weanling piglets after lipopolysaccharide challenge.

The aim of this study was to investigate the effects of dietary ß-hydroxy-ß-methylbutyrate (HMB) on lipopolysaccharide (LPS)-induced muscle atrophy and to investigate the mechanisms involved. Sixty pigs (21 ± 2 days old, 5.86 ± 0.18 kg body weight) were used in a 2 × 3 factorial design and the main factors included diet (0, 0.60%, or 1.20% HMB) and immunological challenge (LPS or saline). After 15 d of treatment with LPS and/or HMB, growth performance, blood parameters, and muscle protein degradation rate were measured. The results showed that in LPS-injected pigs, 0.60% HMB supplementation increased the average daily gain and average daily feed intake and decreased the feed : gain ratio (P < 0.05), with a concurrent increase of lean percentage. Moreover, 0.60% HMB supplementation decreased the serum concentrations of blood urea nitrogen, IL-1ß, and TNF-α and the rate of protein degradation as well as cell apoptosis in selected muscles (P < 0.05). In addition, dietary HMB supplementation (0.60%) regulated the expression of genes involved in mitochondrial biogenesis and increased the phosphorylation of Akt and Forkhead Box O3a (FoxO3a) in selected muscles, accompanied by decreased protein expression of muscle RING finger 1 and muscle atrophy F-box. These results indicate that HMB may exert protective effects against LPS-induced muscle atrophy by normalizing the Akt/FoxO3a axis that regulates ubiquitin proteolysis and by improving mitochondrial biogenesis.

Gut microbiota mediates the protective effects of dietary ß-hydroxy-ß-methylbutyrate (HMB) against obesity induced by high-fat diets.

Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary ß-hydroxy-ß-methylbutyrate (HMB) improves lipid metabolism in a pig model. However, it remains unclear whether HMB blocks obesity through gut microbiota. In this study, we found that HMB reduced body weight, alleviated the whitening of brown adipose tissue, and improved insulin resistance in mice fed a high-fat diet (HFD). High-throughput pyrosequencing of the 16S rRNA demonstrated that HMB administration significantly reversed the gut microbiota dysbiosis in HFD-fed mice, including the diversity of gut microbiota and relative abundances of Bacteroidetes and Firmicutes. Moreover, microbiota transplantation from HMB-treated mice attenuated HFD-induced lipid metabolic disorders. Furthermore, HFD-fed mice showed lower short-chain fatty acids, whereas administration of HMB increased the propionic acid production. Correlation analysis identified a significant correlation between propionic acid production and the relative Bacteroidetes abundance. Sodium propionate treatment also attenuated HFD-induced lipid metabolic disorders. Collectively, our results indicated that HMB might be used as a probiotic agent to reverse HFD-induced obesity, and the potential mechanism was associated with reprogramming gut microbiota and metabolism, especially Bacteroidetes-mediated propionic acid production. In future studies, more efforts should be made to confirm and expand the beneficial effects of HMB to human models.-Duan, Y., Zhong, Y., Xiao, H., Zheng, C., Song, B., Wang, W., Guo, Q., Li, Y., Han, H., Gao, J., Xu, K., Li, T., Yin, Y., Li, F., Yin, J., Kong, X. Gut microbiota mediates the protective effects of dietary ß-hydroxy-ß-methylbutyrate (HMB) against obesity induced by high-fat diets.

α-Ketoisocaproate and ß-hydroxy-ß-methyl butyrate regulate fatty acid composition and lipid metabolism in skeletal muscle of growing pigs.

OBJECTIVES: This study aims to investigate the effects and roles of excess leucine (Leu) versus its metabolites α-ketoisocaproate (KIC) and ß-hydroxy-ß-methyl butyrate (HMB) on fatty acid composition and lipid metabolism in skeletal muscle of growing pigs. METHODS AND RESULTS: Thirty-two pigs with a similar initial weight (9.55 ± 0.19 kg) were fed one of the four diets (basal diet, L-Leu, KIC-Ca and HMB-Ca) for 45 days. Results indicated that dietary treatments did not affect the intramuscular fat (IMF) content (p > 0.05), but differently influenced the fatty acid composition of longissimus dorsi muscle (LM) and soleus muscle (SM). In particular, the proportion of N3 PUFA specifically in LM was significantly decreased in the Leu group and increased in both KIC and HMB group relative to the basal diet group (p < 0.05). Furthermore, pigs fed KIC-supplemented diets exhibited decreased expression of FATP-1, ACC, ATGL, C/EBPα, PPARγ and SREBP-1c in LM and increased expression of FATP-1, FAT/CD36, ATGL and M-CPT-1 in SM relative to the basal diet control (p < 0.05). CONCLUSIONS: These findings indicated that doubling dietary Leu content decreased the percentage of N3 PUFA mainly in glycolytic skeletal muscle, whereas KIC and HMB improved muscular fatty acid composition and altered lipid metabolism in skeletal muscle of growing pigs. The mechanism of action of KIC might be related to the TFs, and the mechanism of action of HMB might be associated with the AMPK-mTOR signalling pathway.