Increased Lipolysis in Adipose Tissues is Associated with Elevation of Systemic Free Fatty Acids and Insulin Resistance in Perilipin Null Mice

Abstract

Elevated plasma levels of free fatty acids (FFAs) are thought to restrict glucose utilization and induce insulin resistance. Plasma FFA concentrations are primarily governed by lipolysis in adipocytes. Perilipin surrounds the lipid droplet in adipocytes and has a dual role in lipolysis regulation. Perilipin null mice studied by two independent laboratories exhibited similar phenotypes of reduced adipose mass and resistance to diet-induced obesity, but have inconsistent metabolic parameters such as plasma levels of FFA, glucose, and insulin. This discrepancy may be due to differences in genetic background, generation, and nutritional status of the animals examined. In this study, we examined the major metabolic parameters in 129/SvEv perilipin null mice fasted for 4 h and observed increased plasma concentrations of FFA, glycerol, glucose, and insulin. An increase in the score for the homeostasis model assessment of insulin resistance index confirmed the insulin resistance in perilipin null mice, which may be attributed to the plasma FFA elevation. Basal lipolysis was increased in adipose tissues or primary adipocytes isolated from perilipin null mice with increased mass and activity of hormone-sensitive lipase and adipose triglyceride lipase. The increased lipolytic action may accelerate FFA efflux from the adipose tissues to the bloodstream, thereby accounting for systemic FFA elevation and, hence, insulin resistance in perilipin null mice.

Correlation Analysis Between Gene Expression Profile of Rat Liver Tissues and High-Fat Emulsion-Induced Nonalcoholic Fatty Liver

“…As was shown in Fig. 5, plin, the gene of lipid droplet coat protein which may induce lipase LIPE to transport from the cytoplasm into lipid drops [24], was up-regulated, and acsl6, which catalyzes fatty acid activation, was remarkably up-regulated, consistent with the enhanced expression of acsl4 in human NAFLD [25]. The expression level of the genes for elongation elovl3 was remarkably induced in HF groups, while elovl6 was repressed.…”

Tauroursodeoxycholic acid inhibits TNF-α-induced lipolysis in 3T3-L1 adipocytes via the IRE-JNK-perilipin-A signaling pathway

“…However, perilipin-A additionally regulates lipase phosphorylation, thereby enhancing lipolytic reactions. A previous study revealed that perilipin-A-null mice exhibit reduced adipose mass, increased basal lipolysis in adipose tissues, and increased expression and activity of hormone-sensitive and adipose triglyceride lipases (11). Increased lipolytic activity may accelerate the efflux of FFAs from adipose tissues to the bloodstream, and therefore insulin resistance in perilipin-A null mice (11).…”

Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle

“…Both FFA and glycerol in plasma have been used as rough estimates of lipolysis and mobilization of fatty acid from adipose tissue (40,41). Interestingly, the plasma level of glycerol was elevated in the CXCL1-transfected mice, suggesting an increased rate of lipolysis in these animals (Fig.…”