Endocrine Abstracts

Introduction: Excessive consumption of free sugars (glucose and fructose) is linked to an increased risk of developing chronic metabolic diseases. Current knowledge of fructose metabolism has focussed on the liver where it is implicated in impaired insulin sensitivity, increased fat accumulation and dyslipidaemia. The long-term effects of elevated fructose consumption on human health are poorly defined and fructose metabolism in subcutaneous adipose tissue, the largest human fat depot, has not been studied.

Methods: Primary human preadipocytes were differentiated in the presence of increasing concentrations (5 mM, 11 mm, 22 mM) of glucose or glucose:fructose (1:1). Differentiation medium was supplemented with ²H₂O (5%) to measure de novo lipogenesis and U-¹³C-fructose to trace fructose metabolism. Intracellular triglycerides (TG) were extracted and fatty acid (FA) composition was measured by gas-chromatography (GC). ²H and ¹³C enrichment of TG-palmitate was assessed using GC-mass spectrometry (MS). Gene expression of lipogenic genes was performed by real-time qPCR.

Results: GC analysis identified a reduction in 16-carbon FAs (62.4 vs. 53.7 mol%, P=4.2×10⁻⁸; 22 mM) and an increase in 18-carbon FAs (25.8 vs. 36.4 mol%, P=7.7×10⁻⁷; 22 mM) at the higher concentrations of fructose. Consistent with increased FA elongase activity mRNA expression of ELOVL6 was upregulated in fructose-treated cells (P<0.05). Total TG content was similar between glucose- and fructose-treated cells across all concentrations and there were no differences in lipogenic gene expression (FASN, ACACA). GC-MS analysis identified equivalent ²H enrichment in TG-palmitate across all fructose concentrations (5 mM: 0.51 vs. 0.54, 11 mM: 0.51 vs 0.53, 22 mM: 0.48 vs. 0.48; 271/270 TTR) whereas ¹³C enrichment in fructose-treated cells increased in a dose-dependent manner (P<0.05).

Conclusions: Human subcutaneous adipocytes metabolise fructose. Fructose favours elongation of 16-carbon to 18-carbon FAs but does not alter total de novo lipogenesis. The functional significance of fructose-induced metabolic changes in subcutaneous adipocytes requires further investigation.