New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases.

The accumulation of excess reactive oxygen species (ROS) can lead to oxidative stress (OS), which can induce gene mutations, protein denaturation, and lipid peroxidation directly or indirectly. The expression is reduced ATP level in cells, increased cytoplasmic Ca2+, inflammation, and so on. Consequently, ROS are recognized as significant risk factors for human aging and various diseases, including diabetes, cardiovascular diseases, and neurodegenerative diseases. Mitochondria are involved in the production of ROS through the respiratory chain. Abnormal mitochondrial characteristics, including mitochondrial OS, mitochondrial fission, mitochondrial fusion, and mitophagy, play an important role in various tissues. However, previous excellent reviews focused on OS-induced diseases. In this review, we focus on the latest progress of OS-induced mitochondrial dynamics, discuss OS-induced mitochondrial damage-related diseases, and summarize the OS-induced mitochondrial dynamics-related signaling pathways. Additionally, it elaborates on potential therapeutic methods aimed at preventing oxidative stress from further exacerbating mitochondrial disorders.

Effects of Dietary Eucommia ulmoides Leaf Extract Supplementation on Growth Performance, Meat Quality, Antioxidant Capacity, and Lipid Metabolism of Finishing Pigs.

This study aimed to investigate the effects of dietary Eucommia ulmoides leaf extract (ELE) on meat quality, antioxidant capacity, and lipid metabolism in finishing pigs. A total of 240 "Duroc × Landrace × Yorkshire" crossbred pigs with an initial weight of 74.70 ± 0.77 kg were randomly assigned to two groups: control group and 0.2% ELE group, with each group containing 10 replicates of 12 pigs per pen (half barrows and half gilts). The data showed dietary 0.2% ELE supplementation did not affect growth performance but tended to reduce the backfat thickness of the finishing pigs (p = 0.07). ELE diets increased pH value (p < 0.05) and meat color score (p = 0.01) and decreased 45 min L* value (p < 0.05), 24 h L* value (p = 0.01), pressurization loss (p = 0.01), and 24 h drip loss (p < 0.05) in longissimus dorsi (LD) muscle, accompanied by an increased (p < 0.05) proportion of monounsaturated fatty acids (MUFA) and decreased polyunsaturated fatty acids (PUFA) (p = 0.06) and n-6/n-3 PUFA ratio (p = 0.05) compared to controls. In addition, ELE supplementation increased inosine monophosphate (IMP) (p = 0.01), sweet amino acids (AAs) (p < 0.05), and total free AA content (p = 0.05) in LD. Meanwhile, increased activity of glutathione peroxidase (p < 0.05) and superoxide dismutase (p < 0.01) in both serum and LD muscle and decreased malondialdehyde content (p < 0.01) in LD muscle were detected with ELE treatment. Moreover, pigs fed ELE had a higher total protein (p < 0.01), albumin (p < 0.05), and high-density lipoprotein cholesterol (p < 0.05) and a lower total cholesterol (p < 0.01) and triacylglycerols (p = 0.06) in serum. Consistently, significant effects of dietary ELE were observed on the relative mRNA expression of lipid metabolism in the backfat and the LD muscle, respectively. ELE attenuated lipogenic processes in backfat, decreasing the relative expression of acetyl-CoA carboxylase and upregulating the relative expression of adipose triacyl glyceride lipase, carnitine palmitoyl transferase 1B, and fatty acid-binding protein 4 (p < 0.05). ELE also decreased the relative expression of CCAAT/enhancer-binding protein α (p < 0.05), fatty acid translocase (p < 0.05), carnitine palmitoyl transferase 1B (p < 0.01), and adipose triacyl glyceride lipase (p < 0.05) in LD muscle (p < 0.05). More specifically, lipogenesis appeared to be inhibited in both LD muscle and backfat, with the difference being that lipolysis was enhanced in backfat and inhibited in LD muscle. In conclusion, dietary ELE supplementation can potentially enhance carcass traits, sensory quality, and nutritional value of pork without negatively affecting intramuscular fat content. The underlying mechanism for these positive effects may be linked to the alterations in lipid metabolism and increased antioxidant capacity induced by ELE.

Leucine regulates lipid metabolism in adipose tissue through adipokine-mTOR-SIRT1 signaling pathway and bile acid-microbe axis in a finishing pig model.

This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs. Twenty-four Duroc × Landrace × Large cross pigs with an average body weight of 68.33 ± 0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group (1 pig per replicate). The dietary treatments were as follows: control group (CON), 0.25% Leu group and 0.50% Leu group. The experimental period was 42 d. The results showed as follows. (1) Compared with the CON, 0.25% and 0.50% Leu increased (P < 0.01) the average daily gain (ADG), while the average backfat thickness (ABT) and the ratio of feed intake to body weight gain (F:G ratio) were decreased (P < 0.05). (2) In the 0.25% Leu group, the relative mRNA expression levels of sterol regulatory element binding protein-1c (SREBP1c), recombinant fatty acid transport protein 1 (FATP1), chemerin and peroxisome proliferator-activated receptor γ (PPARγ) were decreased but the level of fatty acid binding protein 4 (FABP4) and fatty acid translocase (FAT/CD36) were increased in backfat tissue. In the 0.25% Leu group, the protein levels of p-Rictor, p-Raptor, p-eIF4E-binding protein 1 (p-4EBP1), p-silent mating type information regulator 2 homolog 1 (p-SIRT1) and acetylation ribosome s6 protein kinase 1 (Ac-S6K1) were increased (P < 0.05). (3) Compared to the CON, the diversity of gut microbiota in the 0.25% Leu group was increased. Principal component analysis showed that the relative abundance of Bacteroidetes, Lactobacillus and Desulfovibrio was higher in the 0.25% Leu group than the CON, but the relative abundance of Firmicutes, Treponema and Shigella was lower than in the CON (P < 0.05). (4) Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA), which correlate to various degrees with the above microorganisms. In conclusion, Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway, and S6K1 is acetylated at the same time, and the interaction between gut microbiota and bile acid metabolism is also involved.