Search

A growing number of in vivo studies demonstrated that β-hydroxy-β-methyl butyrate (HMB) can serve as a lipid-lowering nutrient. Despite this interesting observation, the use of adipocytes as a model for research is yet to be explored. To ascertain the effects of HMB on the lipid metabolism of adipocytes and elucidate the underlying mechanisms, the 3T3-L1 cell line was employed. Firstly, serial doses of HMB were added to 3T3-L1 preadipocytes to evaluate the effects of HMB on cell proliferation. HMB (50 µM) significantly promoted the proliferation of preadipocytes. Next, we investigated whether HMB could attenuate fat accumulation in adipocytes. The results show that HMB treatment (50 µM) reduced the triglyceride (TG) content. Furthermore, HMB was found to inhibit lipid accumulation by suppressing the expression of lipogenic proteins (C/EBPα and PPARγ) and increasing the expression of lipolysis-related proteins (p-AMPK, p-Sirt1, HSL, and UCP3). We also determined the concentrations of several lipid metabolism-related enzymes and fatty acid composition in adipocytes. The HMB-treated cells showed reduced G6PD, LPL, and ATGL concentrations. Moreover, HMB improved the fatty acid composition in adipocytes, manifested by increases in the contents of n6 and n3 PUFAs. The enhancement of the mitochondrial respiratory function of 3T3-L1 adipocytes was confirmed via Seahorse metabolic assay, which showed that HMB treatment elevated basal mitochondrial respiration, ATP production, H+ leak, maximal respiration, and non-mitochondrial respiration. In addition, HMB enhanced fat browning of adipocytes, and this effect might be associated with the activation of the PRDM16/PGC-1α/UCP1 pathway. Taken together, HMB-induced changes in the lipid metabolism and mitochondrial function may contribute to preventing fat deposition and improving insulin sensitivity.

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 (P0.05). Alanine, aspartate, glutamate, D-glutamine, and D-glutamate metabolism were the main metabolic pathways for the Shaziling pig meat flavor (P0.05). 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 pH

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

The current study was performed to investigate whether dietary β-hydroxy-β-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 β, 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.

Aims Reproduction can induce maternal oxidative stress, and resveratrol is able to alleviate oxidative stress. This study aimed to investigate the protective effects of resveratrol supplementation in mice during pregnancy and lactation. Methods and results Pregnant mice were randomly divided into three groups: (i) Pure water (Con); (ii) Cellulose sodium dissolves with 20 mg kg-1 resveratrol (R1) and (iii) Cellulose sodium dissolves with 40 mg kg-1 resveratrol (R2). The experiment starts at pregnancy and ends at weaning. The results showed that resveratrol increased mammary cell proliferation and the mRNA expressions of UDP glucuronosyltransferase family 1 member A1 (UGT1A1) and cytochrome P450 proteins (CYP1A1), while decreased superoxide dismutase, extracellular (SOD3) in the mammary gland. Further study showed that resveratrol promoted the mRNA expressions of genes involved in mitophagy, such as transcription factor Eβ (Tfeβ), Bcl1lc3β, homosapiens microtubule-associated protein 1 light-chain 3 beta (Map1lc3β), Parkin, sequestosome1 (p62), autophagy-related protein (Atg5) and Beclin-1 (Becn1) in the mammary gland. Moreover, resveratrol increased the abundances of some intestinal microbial species. 40 mg kg-1 resveratrol significantly increased the contents of Acidobacteri, unidentified acidbacteria, Bacilales, Staphylococcaceae and Staphylococcus at phylum, class, order, family and genus level respectively. Conclusion Our results indicate that resveratrol supplementation may promote mammary cell proliferation and antioxidant ability through mitophagy and regulating gut microbiota in pregnant mice. Significance and impact of the study Current study proved that resveratrol could affect mammary cell proliferation and antioxidation capacity during pregnancy and lactation in mice for the first time. The underlying mechanisms may be related to mitophagy and gut microbiota.

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 β-hydroxy-β-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.

Obesity is an issue of great concern to people all over the world. It is accompanied by serious complications, leading to reduced quality of life and higher morbidity and mortality. Over the past few years, there has been an explosion in knowledge about the roles of potential therapeutic agents in obesity management. Among them, amino acid (AA) derivatives, such as taurine, glutathione (GSH), betaine, α-ketoglutarate (AKG), β-aminoisobutyric acid (BAIBA), and β-hydroxy-β-methylbutyrate (HMB), have recently gained popularity due to their beneficial effects on the promotion of weight loss and improvement in the lipid profile. The mechanisms of action of these derivatives mainly include inhibiting adipogenesis, increasing lipolysis, promoting brown/beige adipose tissue (BAT) development, and improving glucose metabolism. Therefore, this review summarizes these AA derivatives and the possible mechanisms responsible for their anti-obesity effects. Based on the current findings, these AA derivatives could be potential therapeutic agents for obesity and its related metabolic diseases.

Aims Leucine supplementation promotes intestinal health, but the mechanism is largely unknown. This study aimed to elucidate the mechanisms underlying the beneficial effects of leucine on intestinal homeostasis. Methods and results Female ICR mice (6-week-old) were randomly assigned into three groups: (i) mice received a basal diet; (ii) mice received a dietary 0·5% crystalline l-leucine supplementation; and (iii) mice received a dietary 1·0% crystalline l-leucine supplementation. Our results showed that leucine supplementation stimulated the secretion of SIgA in mice ileum and expression of cytokines related to SIgA production. Moreover, leucine supplementation improved the expression of mTOR and p70S6K1 expression. Further study showed that leucine supplementation markedly decreased microbiota richness and induced a shift in the Firmicutes : Bacteroidetes ratio in favour of Firmicutes. Conclusions Therefore, our data suggested that leucine supplementation could enhance intestinal health through the regulation of mTOR pathway and promoting SIgA secretion in the mouse intestine, which might be associated with intestinal microbiota. Significance and impact of the study The present study found that dietary leucine supplementation of mice could improve intestinal health by enhancing intestinal SIgA secretion via a nonexclusive mechanism, which might include T cell-dependent pathway, T cell-independent pathway and gut microbiota.

Aims The aims were to examine whether oral sodium propionate supplementation regulate lipid metabolism through modulating gut microbiota. Methods and Results ICR male mice (26·98 ± 0·30 g) were randomly assigned to three groups (n = 10) and fed control diet (Con), high-fat diet (HFD) and HFD plus propionate (Pro) respectively. In this study, we found that HFD increased the weight of final body, inguinal white adipose tissues (iWAT), epididymal white adipose tissue (eWAT) and perirenal white adipose tissue (pWAT), as well as the adipocyte mean area of iWAT and eWAT in mice (P < 0·05), whereas sodium propionate treatment reduced the weight of iWAT and pWAT as well as adipocyte mean area of iWAT in mice fed a HFD (P < 0·05). Moreover, in the iWAT, the mRNA expression of lipogenesis genes, including peroxisome proliferator activated receptor γ, acetyl-CoA carboxylase and carnitine palmitoyl transferase-1β, was upregulated by HFD challenge (P < 0·05), and the elevation of these genes was nearly reversed to the level of control diet-fed mice by sodium propionate treatment. Meanwhile, sodium propionate treatment increased the hormone-sensitive lipase mRNA expression in the iWAT of HFD-fed mice (P < 0·05). High-throughput pyrosequencing of the 16S rRNA demonstrated that sodium propionate treatment significantly recovered the gut microbiota dysbiosis in HFD-fed mice, including the richness and diversity of microbiota and the ratio of Firmicutes to Bacteroidetes. Furthermore, the HFD-induced reductions in colonic levels of butyrate and valerate were reversed by sodium propionate treatment, which also normalized the serum LPS level seen in HFD-fed mice to the levels of the control diet-fed mice. Conclusions Collectively, these results indicated that sodium propionate treatment could improve lipid metabolism in HFD-fed mice, and the potential mechanisms might be via regulating gut microbiota. Significance and Impact of the Study We demonstrated for the first time that oral sodium propionate significantly improved HFD-induced dysbiosis of gut microbiota, indicating that the mitigative effect of propionate for HFD-induced lipid dysmetabolism might be mediated by gut microbiota in mice.

This study aimed to investigate the effects of leucine (Leu) and its metabolites (α-ketoisocaproate (KIC) and β-hydroxy-β-methylbutyrate (HMB)) on muscle protein metabolism in growing pigs fed low-protein diets. 32 pigs (Large White × Landrace, 9.55 ± 0.19 kg) were divided into four groups (basal diet, L-Leu, KIC-Ca, HMB-Ca). Results showed that compared to the control, dietary supplementation of KIC and excess Leu significantly decreased the weight of soleus muscle (SM, P 0.05). In conclusion, HMB, but not KIC or excess Leu, might act as a nutrient signal to stimulate positive protein balance especially in muscles of oxidative fiber-types of growing pigs fed low-protein diets, and these effects might be associated with the Akt signaling.

The aim of this study was to investigate the effects of dietary β-hydroxy-β-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-1β, 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.

This study aimed to investigate the effects of dietary beta-hydroxy beta-methyl butyrate (HMB) supplementation on muscular lipid metabolism in Bama Xiang mini-pigs. Thirty-two piglets (8.58 ± 0.40 kg, barrow) were selected and fed a basal diet supplemented either with 0 (control), 0.13%, 0.64%, or 1.28% HMB for 60 days. Throughout the experiments, they had free access to clean drinking water and diets. Data of this study were analyzed by one-way ANOVA using the SAS 8.2 software package, followed by a Tukey’s studentized range test to explore treatment effects. The results showed that compared to the control, 0.13% HMB decreased the intramuscular fat (IMF) content and increased polyunsaturated fatty acids (PUFAs) in Longissimus thoracis muscle (LTM), and increased the n3 PUFAs in soleus muscles (SM, p &lt, 0.05). Moreover, HMB supplementation led to alterations in the mRNA expression of genes related to lipid metabolism. Serum metabolome profiling showed that in both LTM and SM of Bama Xiang mini-pigs, N-Methyl-l-glutamate was positively correlated with SFA and nummularine A was negatively correlated with C18:3n3 PUFA (p &lt, 0.05). Therefore, N-Methyl-l-glutamate and nummularine A might be potential biomarkers of the HMB-supplemented group. These results suggested that dietary HMB supplementation could decrease the IMF content and increase n3 PUFAs as well as regulate the related metabolites (N-Methyl-l-glutamate and nummularine A) in the serum of 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

This study aimed to explore the effects of beta-hydroxy-beta-methyl butyrate (HMB) on serum metabolic profiles and meat quality of muscles in Wenshi broiler chickens. Birds were fed a basal diet with an additional 0, 0.05, 0.10, or 0.15% HMB, respectively. Results showed that dietary HMB quadratically increased the average daily gain (P = 0.058) and decreased feed:gain (P < 0.05) mainly in the starter phase. At 51 days of age, birds receiving 0.10% HMB diet exhibited less abdominal fat and more breast yield than the control (P < 0.05). Moreover, dietary HMB quadratically decreased the L∗ value and drip loss in selected muscles (P < 0.05) and increased the a∗ value in breast muscle (P < 0.05). Serum metabolome profiling showed that the most differentially abundant metabolites are lipids and lipid-like molecules, including phosphatidylcholines. It was concluded that HMB improved growth performance and meat quality of muscle in broilers.

The aim of this study was to explore the effects of β-hydroxy-β-methylbutyrate (HMB) on intestinal function of lipopolysaccharide (LPS)-challenged piglets.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.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 (P0.05). 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 (P0.05), 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.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.

Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary β-hydroxy-β-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 β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.

OBJECTIVES This study aims to investigate the effects and roles of excess leucine (Leu) versus its metabolites α-ketoisocaproate (KIC) and β-hydroxy-β-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

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.

In recent years, chronic overnutrition, such as consumption of a high-fat diet (HFD), has been increasingly viewed as a significant modifiable risk factor for diseases such as diabetes and certain types of cancer. However, the mechanisms by which HFDs exert adverse effects on human health remains poorly understood. Here, this paper will review the recent scientific literature about HFD-induced inflammation and subsequent development of diseases and cancer, with an emphasis on mechanisms involved. Given the expanding global epidemic of excessive HFD intake, understanding the impacts of a HFD on these medical conditions, gaining great insights into possible underlying mechanisms, and developing effective therapeutic strategies are of great importance.

In this paper, the control system of quadruple tank is designed which is based on the structure of experimental facility of quadruple tank and the method of H∞ loop shaping control. Firstly, The system model of the quadruple tank are acquired with system identification. Then the pre- and post-compensation are selected to make the singular values of the nominal controlled system become the desired open-loop gain. Finally the H∞ loop shaping controller is designed base on the robust stabilization theory. The controller we have obtained will be reduced to the PID controller which is easy to implement. The final controller is firstly used in the simulink environment to get the simulation result. Then the result is verified on the experimental facility of quadruple tank, and the experimental waveforms indicates that the controller have good control performance and robust performance.