Higher Levels of ATGL Are Associated with Exercise-Induced Enhancement of Lipolysis in Rat Epididymal Adipocytes

Abstract

BackgroundIn adipose cells, adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte triacylglyceride hydrolysis, thereby regulating both basal and hormone-stimulated lipolysis. However, little is known about the molecular mechanism(s) underlying habitual exercise-induced adaptive modulation of ATGL in white adipocytes via alteration in transcription regulator and lipolytic cofactors.Methodology/Principal ResultsMale Wistar rats were randomly divided into 2 groups a sedentary control group (CG) and a habitual exercise group (EG). The EG was subjected to running on a treadmill set at 5 days per week for 9 weeks. The CG was not subjected to running on a treadmill. In the EG, levels of ATGL mRNA and protein were elevated with a significant increase in lipolysis compared with the CG, accompanied by a significant increase in associations of CGI-58 with ATGL protein. Under these conditions, an upregulation of peroxisome proliferation-activated receptorg-2 (PPARg-2) was observed. In the EG, the addition of rosiglitazone further significantly increased the levels of ATGL protein compared with the CG. However, attenuated levels of the ATGL protein in adipocytes were obtained by the addition of insulin, which is known to inhibit the expression of ATGL, in both types of groups. Actually, levels of plasma insulin were significantly reduced in the EG compared with the CG.ConclusionsThese data suggest that elevated levels of ATGL are involved in the exercise-induced enhancement of lipolysis in primary adipocytes. The exact mechanism(s) underlying this phenomenon is associated, at least in part, with upregulated transcriptional activation of PPARg-2. In addition, exercise-induced lower circulation levels of insulin also correlate with habitual exercise-induced higher levels of ATGL in primary adipocytes.

Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling

“…Further, the role of adipose triglyceride lipase (ATGL) has long been investigated for its regulation by insulin, expression alterations during obesity as well as exercise-induced enhancement for lipolysis in adipocytes. Thus, exercise likely induces a panoply of events that sculpt the lipidome of scWAT and BAT tissue (Burstein et al, 1992; Koivisto and Yki-Jarvinen, 1987; Stanford et al, 2015b),(Jocken et al, 2007; Kershaw et al, 2006; Ogasawara et al, 2012). Together, these studies provide a rationale to study these phospholipases in the regulation of phospholipids and mitochondrial function in response to exercise (Jocken et al, 2007; Kershaw et al, 2006; Mancuso et al, 2010; Ogasawara et al, 2012); future studies will focus on exercise-induced regulation of these phospholipases and how they can potentially contribute to insulin sensitivity.…”

Acute exercise regulates adipogenic gene expression in white adipose tissue

“…FA mobilization from WAT is regulated by the activity of hormone-sensitive lipase (HSL), monoglyceride lipase (MGL) and adipose triglyceride lipase (ATGL) [39]. Since exercise promotes lipolysis from adipocytes by activating HSL and ATGL [40, 41], exercise-induced hypotrophy of adipocytes is, at least in part, responsible for the reduction of WAT mass in obese individuals. However, it remains uncertain whether endurance exercise regulates adipogenesis by altering adipogenic gene expression.…”

Lipolysis, lipogenesis, and adiposity are reduced while fatty acid oxidation is increased in visceral and subcutaneous adipocytes of endurance-trained rats

“…[1][2][3][4] Importantly, analyses of NEFA rate of appearance (Ra) [4][5][6] during exercise revealed that this variable was significantly reduced as a result of training, which is also in support of a reduction in WAT lipolysis with endurance training. However, at odds with these findings are the results of studies measuring catecholamine-stimulated glycerol release in isolated adipocytes from humans [7][8][9][10][11] and rats, [12][13][14][15] which report increased WAT lipolysis after a period of endurance training. Additional studies have reported lipolysis to be either reduced in isolated rat adipocytes 16 or unaltered when assessed in situ by the microdialysis technique in human WAT 17 following a period of endurance training.…”