Upregulation of Pnpla2 and Abhd5 and downregulation of G0s2 gene expression in mesenteric white adipose tissue as a potential reason for elevated concentration of circulating NEFA after removal of retroperitoneal, epididymal, and inguinal adipose tissue.

Agnieszka Dettlaff-Pokora,Tomasz Sledzinski,Julian Swierczynski

doi:10.1007/s11010-016-2800-4

Agnieszka Dettlaff-Pokora, Tomasz Sledzinski + Show 1 more

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https://doi.org/10.1007/s11010-016-2800-4

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Abstract

Elevated concentrations of circulating non-esterified fatty acids (NEFA) were reported in (a) humans with lipodystrophy, (b) humans following bariatric surgery, and (c) transgenic mice with reduced amounts of adipose tissue. Paradoxically, these findings suggest that the reduction of adipose tissue mass is associated with elevated circulating NEFA concentrations. To explain a molecular background of this phenomenon, we analyzed the effects of surgical removal of inguinal, epididymal, and retroperitoneal white adipose tissue (WAT) on (a) circulating NEFA concentrations, (b) expression of Pnpla2, a gene that encodes adipose triglyceride lipase (ATGL), genes encoding abhydrolase domain containing 5 (ABHD5) and G0/G1 switch 2 (G0S2), i.e., a coactivator and inhibitor of ATGL, respectively, and (c) expression of Lipe gene coding hormone-sensitive lipase (HSL) in mesenteric WAT. Reduction of adipose tissue mass resulted in an increase in circulating NEFA concentration, which was associated with (a) an increase in the expressions of Pnpla2 and Abhd5, (b) decrease in G0s2 expression, and (c) upregulation of Lipe expression, all measured on both mRNA and protein levels in mesenteric WAT of male rats. The rate of lipolysis in mesenteric WAT explants and isolated adipocytes from lipectomized rats was significantly higher than that from the controls. In conclusion, upregulation of Pnpla2 expression and activation of ATGL (due to an increase in ABHD5 and decrease in G0S2 levels), as well as a coordinated interplay of these genes with Lipe in mesenteric WAT, contribute, at least in part, to an increase in the concentration of circulating NEFA in rats with reduced fat mass.

Highlights

Excess of adipose tissue is generally believed to be associated with increased risk of metabolic syndrome, insulin resistance, and diabetes mellitus [1,2,3,4]
The data presented in this paper indicate that following surgical reduction of epididymal and retroperitoneal white adipose tissue (WAT) mass and total surgical removal of inguinal WAT, circulating non-esterified fatty acids (NEFA) concentration significantly increases
It is generally accepted that most circulating NEFA concentrations originate from lipolysis in adipose tissue

Summary

Introduction

Excess of adipose tissue (e.g., in obese subjects) is generally believed to be associated with increased risk of metabolic syndrome, insulin resistance, and diabetes mellitus [1,2,3,4]. Complete lack or deficiency of adipose tissue, as seen in lipodystrophy and lipoatrophy, is associated with an increase in the concentration of circulating NEFA [8], greater risk of metabolic syndrome, insulin resistance, diabetes mellitus, and cardiovascular diseases [9,10,11,12,13]. These abnormalities result, at least in part, from accumulation of ectopic triacylglycerols in the liver and muscles, rather than in adipocytes [14]. A molecular background of the increase in circulating NEFA

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