Abstract

White adipose tissue (WAT) produces large amounts of lactate and glycerol from glucose. We used mature epididymal adipocytes to analyse the relative importance of glycolytic versus lipogenic glycerol in adipocytes devoid of external stimuli. Cells were incubated (24/48 h) with 7/14 mM glucose; half of the wells contained 14C-glucose. We analysed glucose label fate, medium metabolites, and the expression of key genes coding for proteins controlling glycerol metabolism. The effects of initial glucose levels were small, but time of incubation increased cell activity and modified its metabolic focus. The massive efflux of lactate was uniform with time and unrelated to glucose concentration; however, glycerol-3P synthesis was higher in the second day of incubation, being largely incorporated into the glycerides-glycerol fraction. Glycerophosphatase expression was not affected by incubation. The stimulation of glycerogenic enzymes’ expression was mirrored in lipases. The result was a shift from medium glycolytic to lipolytic glycerol released as a consequence of increased triacylglycerol turnover, in which most fatty acids were recycled. Production of glycerol seems to be an important primary function of adipocytes, maintained both by glycerogenesis and acyl-glycerol turnover. Production of 3C fragments may also contribute to convert excess glucose into smaller, more readily usable, 3C metabolites.

Highlights

  • Intact white adipose tissue (WAT) secrete significant amounts of glycerol[1]

  • In most tissues, including White adipose tissue (WAT), acyl-CoA can be alternatively synthesized from extracellular fatty acids[11], such as those released by lipoprotein lipase

  • Using primary cultures of mature epidydimal adipocytes, we have found that under conditions of maintained glucose availability, the cells convert a sizeable part of glucose to 3C metabolites such as lactate and glycerol

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Summary

Introduction

Intact white adipose tissue (WAT) (and isolated adipocytes) secrete significant amounts of glycerol[1]. WAT capacity to recycle free glycerol is limited[4], but glycerol is a main substrate for hepatic gluconeogenesis[5], and a viable substrate for energy or TAG synthesis in many tissues[6, 7]. In most tissues, including WAT, acyl-CoA can be alternatively synthesized from extracellular fatty acids[11], such as those released by lipoprotein lipase. Both 3C fragments, being good lipogenic substrates[10, 14], free glycerol does not seem to be used by WAT in significant amounts, neither for lipogenesis nor as energy substrate[15], and is not recycled in significant proportions to glycerol-3P16, 17. Glycerol is a good substrate for energy, since it can be rapidly incorporated into the glycolytic pathway[22]

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