Exploring complex and heterogeneous correlations on hypergraph for the prediction of drug-target interactions.

The continuous emergence of drug-target interaction data provides an opportunity to construct a biological network for systematically discovering unknown interactions. However, this is challenging due to complex and heterogeneous correlations between drug and target. Here, we describe a heterogeneous hypergraph-based framework for drug-target interaction (HHDTI) predictions by modeling biological networks through a hypergraph, where each vertex represents a drug or a target and a hyperedge indicates existing similar interactions or associations between the connected vertices. The hypergraph is then trained to generate suitably structured embeddings for discovering unknown interactions. Comprehensive experiments performed on four public datasets demonstrate that HHDTI achieves significant and consistently improved predictions compared with state-of-the-art methods. Our analysis indicates that this superior performance is due to the ability to integrate heterogeneous high-order information from the hypergraph learning. These results suggest that HHDTI is a scalable and practical tool for uncovering novel drug-target interactions.

[Effects of different types of exercise on lipid uptake, synthesis and oxidation in skeletal muscles of insulin-resistant rats].

The present study aims to investigate the effects of aerobic exercise and resistance exercise on lipid metabolism of skeletal muscle in high-fat diet (HFD)-induced insulin-resistant (IR) rats and the underlying mechanisms. Male Sprague-Dawley (SD) rats at age of 10 weeks were fed with HFD for 10 weeks to establish IR model. The IR rats were then randomly assigned into 3 groups, including IR control (IR) group, aerobic exercise (AE) group and resistance exercise (RE) group. An additional chow diet sedentary control (CON) group was used as well. Fasting blood glucose (FBG), insulin (FIN), glucagon and lipids, as well as triacylglycerol (TG), free fatty acids (FFA), and the protein expression of fatty acid translocase/cluster of differentiation 36 (FAT/CD36), carnitine palmitoyltransferase-1 (CPT-1), stearoyl-CoA desaturase-1 (SCD-1) and peroxisome proliferators-activated receptors γ (PPARγ) in skeletal muscles were measured after 8-week exercise interventions. The results showed that the contents of FBG, FIN, and LDL-C were increased by IR compared with CON group, and significantly decreased by aerobic exercise and resistance exercise; while aerobic exercise induced an increase in HDL-C as well. Furthermore, IR exhibited no significant effects on TG content of skeletal muscles, but significantly increased FFA level. Both aerobic and resistance exercise led to a decrease in TG content, and FFA level was increased by aerobic exercise but deceased by resistance exercise. In addition, the protein expression of FAT/CD36, SCD-1 and PPARγ was increased and that of CPT-1 was decreased by IR, while both types of exercise resulted in a decrease in the protein expression of FAT/CD36, SCD-1 and PPARγ, and an increase in CPT-1. In conclusion, aerobic and resistance exercise may attenuate IR through decreasing HFD-induced ectopic fat deposition and increasing ß-oxidation of fatty acids in skeletal muscle cells, and resistance exercise shows a greater improvement in lipid metabolism of skeletal muscles than aerobic exercise.

Endurance Training Counteracts the High-Fat Diet-Induced Profiling Changes of ω-3 Polyunsaturated Fatty Acids in Skeletal Muscle of Middle-Aged Rats.

PURPOSE: To investigate the effects of endurance training on the content of ω-3 polyunsaturated fatty acids (PUFAs) and their distribution among lipid classes in skeletal muscle in middle aged, high-fat diet fed rats. METHOD: Thirty 10-month old male Sprague Dawley (SD) rats were assigned to four groups. Two groups of rats remained sedentary and were fed chow diet (C group), or high-fat diet (H group), respectively. The other two groups of rats were subjected to endurance training while maintaining their chow diet (EC group), or high-fat diet (EH group). After 16 weeks endurance training and/or diet intervention, the content of ω-3 PUFAs and ω-3 PUFA-containing lipids in rat soleus muscle were analyzed by lipidomics. RESULTS: Rats fed a high-fat diet exhibited decreased overall amount of ω-3 PUFAs in soleus muscle, while endurance training preserved the total amount of ω-3 PUFAs. Both the endurance training and high-fat diet alone changed the profiles of ω-3 PUFAs in different lipid classes. Specifically, the amount of triacylglycerol (TG), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylglycerol (PG) containing ω-3 PUFAs in soleus muscle was increased by endurance training, but the amount of lysophosphatidylenthanol (LPE), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), cardiolipin (CL), phosphatidic acid (PA), and phosphatidylinositol (PI) was decreased. The high-fat diet induced a decrease of ω-3 PUFAs in TG, LPE, LPS, CL, platelet activating factor (PAF), PC, phosphatidylethanolamine (PE), and phosphatidylserine (PS), and an increase in LPC, LPI, PA, and PG. In addition, the effects of the endurance training on ω-3 PUFAs in skeletal muscle was also evident in high-fat diets fed rats, which counteracts the profiling changes caused by high-fat diet feeding. CONCLUSION: The beneficial effects of endurance training on skeletal muscle may be achieved to some extent through recovering the content of ω-3 PUFAs that has been decreased by high-fat diet feeding.

[Role of skeletal muscle fat ectopic deposition in insulin resistance induced by high-fat diet].

Consumption of high-fat diet leads to the increase of fat intake and consequent excess storage of fat in the body. When the regular adipose tissues reach their capacity to store fat, ectopic fat is stored around and within non-adipose tissues, such as the liver and skeletal muscle, which plays important roles in glucose metabolism. Hence ectopic fat accumulation in major insulin target tissues is a critical determinant of insulin resistance (IR) and various related metabolic syndromes. Recent studies have shown that skeletal muscle lipid accumulation is more closely related with IR than general obesity and accounts for approximately 80%-90% type 2 diabetes, since the skeletal muscle is the largest glucose disposal site. Therefore, the association between skeletal muscle lipid and IR has attracted more and more research interest. This review summarized the role of ectopic skeletal muscle lipid in IR induced by high-fat diet and its possible mechanisms.