Rosiglitazone remodels the lipid droplet and britens human visceral and subcutaneous adipocytes ex vivo

Mi-Jeong Lee,Sukanta Jash,Jessica E.C Jones,Vishwajeet Puri,Susan K Fried

doi:10.1194/jlr.m091173

Mi-Jeong Lee, Sukanta Jash + Show 3 more

Open Access

https://doi.org/10.1194/jlr.m091173

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Abstract

Treatment with PPARγ agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood. To examine the ex vivo metabolic effects of rosiglitazone (Rosi), we cultured explants of human visceral (omental) and abdominal subcutaneous adipose tissues for 7 days. Rosi increased mRNA levels of transcriptional regulators of brite/beige adipocytes (PGC1α, PRDM16), triglyceride synthesis (GPAT3, DGAT1), and lipolysis (ATGL) similarly in adipose tissues from both depots. In parallel, Rosi increased key modulators of FA oxidation (UCP1, FABP3, PLIN5 protein), rates of FA oxidation, and protein levels of electron transport complexes, suggesting an enhanced respiratory capacity as confirmed in newly differentiated adipocytes. Rosi led to the formation of small lipid droplets (SLDs) around the adipocyte central lipid droplet; each SLD was decorated with redistributed mitochondria that colocalized with PLIN5. SLD maintenance required lipolysis and FA reesterification. Rosi thus coordinated a structural and metabolic remodeling in adipocytes from both visceral and subcutaneous depots that enhanced oxidative capacity. Selective targeting of these cellular mechanisms to improve adipocyte FA handling may provide a new approach to treat metabolic complications of obesity and diabetes.

Highlights

Treatment with PPAR agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood
Rosi induced expression of mRNA and proteins involved in FA metabolism in brown adipose tissue (BAT), including UCP1, PLIN5, and FABP3 [25, 41], in both Om and abdominal subcutaneous adipose tissue (ASAT) (Fig. 1A, B)
As we found that most of the mitochondria were surrounding the clusters of small lipid droplet (SLD), not the central droplet, and PLIN5 was induced in brite adipocytes, we evaluated whether the PLIN coating of the large and small droplets differed

Summary

Introduction

Treatment with PPAR agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood. Rosi coordinated a structural and metabolic remodeling in adipocytes from both visceral and subcutaneous depots that enhanced oxidative capacity. Selective targeting of these cellular mechanisms to improve adipocyte FA handling may provide a new approach to treat metabolic complications of obesity and diabetes.—Lee, M-J., S. The adipocyte must cope with an increased flux of FAs from the diet and higher basal lipolysis [2, 3] If these FAs are not efficiently esterified or oxidized, unbound FAs within the cell cause lipotoxic stress with deleterious consequences for adipocyte metabolic and endocrine function [4,5,6].

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