Fatty Acid Metabolism and Idiopathic Pulmonary Fibrosis

Fatty acid metabolism, including the de novo synthesis, uptake, oxidation, and derivation of fatty acids, plays several important roles at cellular and organ levels. Recent studies have identified characteristic changes in fatty acid metabolism in idiopathic pulmonary fibrosis (IPF) lungs, which implicates its dysregulation in the pathogenesis of this disorder. Here, we review the evidence for how fatty acid metabolism contributes to the development of pulmonary fibrosis, focusing on the profibrotic processes associated with specific types of lung cells, including epithelial cells, macrophages, and fibroblasts. We also summarize the potential therapeutics that target this metabolic pathway in treating IPF.

The Role of Fatty Acid Metabolism in Drug Tolerance of Mycobacterium tuberculosis

Understanding the mechanisms underlying M. tuberculosis adaptive strategies to achieve drug tolerance is crucial for the identification of new targets and the development of new drugs. Here, we show that acetate medium triggers a drug-tolerant state in M. tuberculosis when challenged with antituberculosis (anti-TB) drugs.

Impacts of Betaine Addition in Sow and Piglet's Diets on Growth Performance, Plasma Hormone, and Lipid Metabolism of Bama Mini-Pigs

The present study evaluated the effects of betaine addition in sow and piglet's diets on growth performance, plasma hormone, and lipid metabolism of Bama mini-pigs. A total of 26 pregnant Bama mini-pigs and 104 weaned piglets were selected and divided into different dietary treatment groups (details in “Materials and Methods”). Blood and muscle samples were collected at 65-, 95-, and 125-day-old, respectively. The results showed that betaine addition in sow-offspring diets increased (P < 0.05) the body weight at 125-day-old, average daily gain from 35- to 65-day-old, and average daily feed intake at 35–65 and 35–95 days old of pigs compared with the control group. Betaine addition in sow-offspring diets increased (P < 0.05) the plasma gastrin level at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the plasma peptide YY and leptin levels at 65-day-old pigs. In the longissimus dorsi muscle of pigs, betaine addition in sow and sow-offspring diets increased (P < 0.05) the C12:0 content at 65-day-old while decreased at 95-day-old. Moreover, betaine addition in sow-offspring diets increased the C24:0 content and decreased the C18:1n9t content at 125-day-old (P < 0.05). In the biceps femoris muscle, the contents of C12:0 at 65-day-old and C20:4n6 at 125-day-old were decreased (P < 0.05) after the betaine addition in both sow and piglet's diets. In addition, betaine addition in sow diets decreased (P < 0.05) the C20:0 content at 125-day-old, while betaine addition in sow-offspring diets increased the C18:3n6 and decreased C24:0 contents at 65-day-old pigs (P < 0.05). In the psoas major muscle, betaine addition in sow and sow-offspring diets decreased (P < 0.05) the contents of C18:1n9t at 65-day-old and C20:1 at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the intramuscular fat content at 125-day-old. Moreover, betaine addition in sow-offspring diets was also associated with muscle lipid deposition and metabolisms by regulating the gene expressions related to fatty acid metabolism. These findings suggested that betaine addition in sow-offspring diets could improve the growth performance, whereas betaine addition in both sow and sow-offspring diets could enhance lipid quality by altering plasma hormone level and fatty acid composition and regulating the gene expressions related to fatty acid metabolism.

Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells

Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism perturbations. However, the exact alterations in substrate metabolism during ID are poorly defined. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the present study investigated changes in major metabolic substrate utilisation in the context of ID or upon transferrin rescue. Typically, during hiPSC-CM differentiation, the greatest increase in total metabolic output and rate was seen in fatty acid metabolism. When ID was induced, hiPSC-CMs displayed increased reliance on glycolytic metabolism, and six TCA cycle, five amino acid, and four fatty acid substrates were significantly impaired. Transferrin rescue was able to improve TCA cycle substrate metabolism, but the amino acid and fatty acid metabolism remained perturbed. Replenishing iron stores partially reverses the adverse metabolic changes that occur during ID. Understanding the changes in metabolic substrate utilisation and their modification may provide potential for discovery of new biomarkers and therapeutic targets in cardiovascular diseases.

High-Salt Attenuates the Efficacy of Dapagliflozin in Tubular Protection by Impairing Fatty Acid Metabolism in Diabetic Kidney Disease

High-salt intake leads to kidney damage and even limits the effectiveness of drugs. However, it is unclear whether excessive intake of salt affects renal tubular energy metabolism and the efficacy of dapagliflozin on renal function in diabetic kidney disease (DKD). In this study, we enrolled 350 DKD patients and examined the correlation between sodium level and renal function, and analyzed influencing factors. The results demonstrated that patients with macroalbuminuria have higher 24 h urinary sodium levels. After establishment of type 2 diabetes mellitus model, the animals received a high-salt diet or normal-salt diet. In the presence of high-salt diet, the renal fibrosis was aggravated with fatty acid metabolism dysregulation. Furthermore, Na+/K+-ATPase expression was up-regulated in the renal tubules of diabetic mice, while the fatty acid metabolism was improved by inhibiting Na+/K+-ATPase of renal tubular epithelial cells. Of note, the administration with dapagliflozin improved renal fibrosis and enhanced fatty acid metabolism. But high salt weakened the above-mentioned renal protective effects of dapagliflozin in DKD. Similar results were recapitulated in vitro after incubating proximal tubular epithelial cells in high-glucose and high-salt medium. In conclusion, our results indicate that high salt can lead to fatty acid metabolism disorders by increasing Na+/K+-ATPase expression in the renal tubules of DKD. High salt intake diminishes the reno-protective effect of dapagliflozin in DKD.