Triglyceride Synthesis in Epididymal Adipose Tissue

Ilya R Bederman,Steven Foy,Visvanathan Chandramouli,James C Alexander,Stephen F Previs

doi:10.1074/jbc.m808668200

Ilya R Bederman, Steven Foy + Show 3 more

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https://doi.org/10.1074/jbc.m808668200

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Abstract

The obesity epidemic has generated interest in determining the contribution of various pathways to triglyceride synthesis, including an elucidation of the origin of triglyceride fatty acids and triglyceride glycerol. We hypothesized that a dietary intervention would demonstrate the importance of using glucose versus non-glucose carbon sources to synthesize triglycerides in white adipose tissue. C57BL/6J mice were fed either a low fat, high carbohydrate (HC) diet or a high fat, carbohydrate-free (CF) diet and maintained on 2H2O (to determine total triglyceride dynamics) or infused with [6,6-(2)H]glucose (to quantify the contribution of glucose to triglyceride glycerol). The 2H2O labeling data demonstrate that although de novo lipogenesis contributed approximately 80% versus approximately 5% to the pool of triglyceride palmitate in HC- versus CF-fed mice, the epididymal adipose tissue synthesized approximately 1.5-fold more triglyceride in CF- versus HC-fed mice, i.e. 37+/-5 versus 25+/-3 micromolxday(-1). The [6,6-(2)H]glucose labeling data demonstrate that approximately 69 and approximately 28% of triglyceride glycerol is synthesized from glucose in HC- versus CF-fed mice, respectively. Although these data are consistent with the notion that non-glucose carbon sources (e.g. glyceroneogenesis) can make substantial contributions to the synthesis of triglyceride glycerol (i.e. the absolute synthesis of triglyceride glycerol from non-glucose substrates increased from approximately 8 to approximately 26 micromolxday(-1) in HC- versus CF-fed mice), these observations suggest (i) the importance of nutritional status in affecting flux rates and (ii) the operation of a glycerol-glucose cycle.

Highlights

Epidemiological trends in the development of obesity [1,2,3,4] and its association with various diseases have generated interest in the study of lipid synthesis and mobilization
Chen et al [7] have suggested that following the administration of 2H2O, it is possible to quantify the contribution of glucose versus glyceroneogenesis to triglyceride glycerol in vivo; this requires that one measures the proportion of triglyceride glycerol containing one and two 2H and applies a combinatorial method to determine the number of exchangeable hydrogens
Consistent with an increase in total fatty acids, we observed an increase in triglyceride glycerol between 3 and 28 days, i.e. in high carbohydrate (HC)-fed mice epididymal glycerol increased from 326 Ϯ 36 to 393 Ϯ 49 ␮mol (p Ͻ 0.01) and in CF-fed mice from 329 Ϯ 27 to 512 Ϯ 66 ␮mol (p Ͻ 0.01)

Summary

Introduction

Epidemiological trends in the development of obesity [1,2,3,4] and its association with various diseases have generated interest in the study of lipid synthesis and mobilization. Chen et al [7] have suggested that following the administration of 2H2O, it is possible to quantify the contribution of glucose versus glyceroneogenesis to triglyceride glycerol in vivo; this requires that one measures the proportion of triglyceride glycerol containing one and two 2H and applies a combinatorial method to determine the number of exchangeable hydrogens (i.e. the “n”). This logic assumes that the production of ␣-glycerol-3-phosphate from glucose results in an n of 3.5, whereas the production of ␣-glycerol3-phosphate from lactate, pyruvate, etc. Mice were fed a high carbohydrate or a carbohydrate-free diet to determine the maximum/minimum potentials of glucose versus non-glucose-derived sources to triglyceride dynamics, 2H2O was used to quantify the rates of de novo lipogenesis and the total rates of triglyceride synthesis and degradation, and [6,6-2H]glucose was used to measure the contribution of glucose to triglyceride glycerol

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