305-OR: Adipose Tissue Perilipin 1 Insulin Responsiveness in Obesity

Adipose tissue (AT) lipolysis is dysregulated in obesity and type 2 diabetes, failing to respond appropriately to the lipolytic suppressive effects of insulin resulting in high free fatty acid (FFA) efflux from AT. Perilipin 1 (PLIN1) is an intracellular adipocyte protein and the primary lipid droplet coat protein. Phosphorylation of PLIN1 is purported to activate and provide access to the lipid droplet surface for lipolytic enzymes. Conversely, dephosphorylation in response to insulin protects the lipid droplet. To test the hypothesis that PLIN1 phosphorylation status is dysregulated in obesity, we recruited 8 lean and 20 volunteers with obesity who underwent a two-step hyperinsulinemic-euglycemic clamp with a [U-¹³C]-palmitate tracer to quantify FFA kinetics and their AT response to insulin with regards to FFA release (IC₅₀ FFA), we performed abdominal (UBSQ) and thigh subcutaneous adipose tissue biopsies at baseline and at each clamp step. We measured adipocyte cell size, total PLIN1 protein concentrations and phospho-PLIN1-Ser⁵²² in adipose samples. Intra-individual total PLIN1 protein content/1000 adipocytes did not change in either thigh or UBSQ at either baseline or during each clamp step. Total PLIN1/1000 cells was positively correlated with adipocyte size in UBSQ (ρ = 0.85, p <0.001) and thigh (ρ = 0.86, p <0.001). There was a step wise reduction in PLIN Phosphorylation in both depots in response to each insulin clamp step from baseline (UBSQ and thigh, baseline vs. 1^st step clamp vs. 2^nd step clamp, all p < 0.01) There was no difference between the ratio of phosphorylated PLIN to total PLIN (pPLIN/PLIN) between UBSQ and thigh samples. IC₅₀ FFA was correlated Total PLIN1/1000 cells in UBSQ (ρ = 0.46, p = 0.02), but not in thigh adipose. After correcting for adipocyte size, the relationship between IC₅₀ FFA and Total PLIN1 was no longer significant.

In conclusion, PLIN1 content or responsiveness doesn’t appear to be defective in adults with obesity that have reduced ability of insulin to suppress systemic FFA release.