VIDEO: Adipogenic genes upregulated in high-BMI sucralose users

CHICAGO – When fat tissue from individuals with obesity was exposed to the artificial sweetener sucralose, there was significant upregulation of genes that promote intracellular glucose transport. Genes known to be adipogenic and those governing sweet taste receptors also were significantly upregulated with sucralose exposure.

“Effects of sucralose are particularly more detrimental in obese individuals who are prediabetic or diabetic, rather than nonobese consumers of low-calorie sweetener,” said Sabyasachi Sen, MD, during a press conference at the annual meeting of the Endocrine Society.

These new findings, together with in vitro examination of human adipose-derived mesenchymal stromal cells (MSCs) exposed to sucralose, are helping solve the puzzle of how a sweetener that delivers no energy may contribute to metabolic derangement, said Dr. Sen, professor of endocrinology at George Washington University in Washington.

Dr. Sen and his collaborators first exposed the MSCs to concentrations of sucralose ranging from 0 mM to 0.2 mM – a physiologic level for high sucralose consumers – to the supraphysiologic concentration of 1 mM.

The adipogenic genes CEBPa and FABP4 were upregulated in the sucralose-exposed MSCs, which also showed more intracellular fat droplet accumulation. Reactive oxygen species increased in the MSCs in a dose-dependent fashion as well, said Dr. Sen in a video interview.

All of this upregulation, said Dr. Sen, was pushing the MSCs toward becoming fat cells. “At the same time, we saw that there are certain genes that were upregulating that were allowing more glucose to enter the cell.” The increase in reactive oxygen species paralleled what was seen in a similar model that used glucose rather than sucralose, he said.

The investigators then took subcutaneous fat biopsies from four normal-weight individuals (body mass index, 23.4-24.8 kg/m²), and from 14 obese individuals (BMI, 32-64 kg/m²). Each group had sucralose users and nonusers. Using mRNA gene expression profiles, they saw that glucose transporter genes, adipogenic genes, and antioxidant genes were upregulated among sucralose consumers with obesity, significantly more than for the normal-weight participants.