1-2-dilauroylphosphatidylcholine and Insulin-Resistance

Obesity causes the development of insulin resistance and type 2 diabetes. Phosphatidylcholine (PPC) has been reported to increase hepatic insulin sensitivity and lipolysis in adipose tissue to resolve local obesity. In this study, we proposed 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), the main active species of PPC, as an effective substance for the treatment of obesity-mediated disorders such as impaired fat metabolism and insulin resistance. Therefore, we investigated the potential lipolytic effects of DLPC on adipocytes and insulin signaling in muscle cells. In this study, DLPC-treated 3T3-L1 adipocytes showed enhanced tumor necrosis factor α (TNF-α) release. Suppression of TNF-α by short interfering RNA (siRNA) mitigated DLPC-induced lipolysis and apoptosis. DLPC treatment increased peroxisome proliferator-activated receptor α (PPARα) expression levels in C2C12 myocytes. siRNA-mediated suppression of PPARα abrogated the suppressive effects of DLPC on palmitate-induced inflammation and insulin resistance. In conclusion, DLPC enhanced lipolysis and apoptosis via a TNFα-dependent pathway in adipocytes and attenuated palmitate-induced insulin resistance through PPARα-mediated suppression of inflammation in myocytes.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Apoptosis; Cell Line; Inflammation; Insulin Resistance; Lipolysis; Mice; Muscle Fibers, Skeletal; Palmitates; Phosphatidylcholines; Tumor Necrosis Factor-alpha

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.

Topics: Animals; Bile Acids and Salts; Blood Glucose; Cell Line; Disease Models, Animal; Fatty Liver; HeLa Cells; Homeostasis; Humans; Hypoglycemic Agents; Insulin Resistance; Ligands; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphatidylcholines; Protein Binding; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Triglycerides

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Bile Acids and Salts; Fatty Liver; Humans; Insulin Resistance; Liver; Mice; Phosphatidylcholines; Receptors, Cytoplasmic and Nuclear; Signal Transduction