AT ENDO 2017

ORLANDO (FRONTLINE MEDICAL NEWS) – Consumption of low-calorie sweeteners was associated with upregulation of gene expression for glucose transporters in experiments using human mesenchymal stromal cells and adipose tissue, according to new research.

The effect was strongest in individuals with obesity.

Using human subcutaneous fat tissue taken from individuals who consumed low-calorie sweeteners, Sabyasachi Sen, MD, of George Washington University, Washington, and his colleagues showed that these cells had at least a twofold overexpression of glucose transporters. Also overexpressed were sweet taste receptors and adipogenic genes.

The findings add to the “increasing scientific evidence that these sweeteners promote metabolic dysfunction,” Dr. Sen said in a statement released at the annual meeting of the Endocrine Society.

Dr. Sen and his colleagues first tested the effects of both physiologic and supraphysiologic doses of sucralose on human adipose-derived mesenchymal stromal cells (MSCs). In the presence of adipogenic media, sucralose was added to the MSCs for a period of 12 days.

When sucralose was added at a concentration of 0.2 millimoles (mM), the investigators detected “small but reproducible” increases in expression of adiponectin, as well as genes that encode for the production of fatty acid binding proteins (FABP4) and proteins implicated in body weight homeostasis (CEBPA). Increases ranged from 1.04- to 1.32-fold.

Dr. Sen explained that the 0.2 mM concentration approximates the amount of sucralose in the tissues of individuals with high low-calorie sweetener consumption.

These effects were more pronounced when the sucralose concentration was raised to a supraphysiologic 1 mM. Then, CEBPA expression increased by a factor of 3.45, adiponectin by 4.39, and FABP4 by 4.06. More intracellular fat droplets were seen with higher sucralose concentrations in a “dose dependent fashion,” said Dr. Sen and his colleagues.

The researchers also took subcutaneous fat biopsies from four individuals of healthy weight (body mass index [BMI] less than 24.9 kg/m2) and from four individuals with obesity (BMI greater than 24.9). Participants ranged in age from 36 years to 60 years.

Individuals in both groups had kept a 7-day food diary before the biopsies were taken, so Dr. Sen and his coinvestigators knew whether or not they had consumed low-calorie sweeteners and in what quantity. Reported sweeteners were sucralose, acesulfame-potassium, and aspartame.

The adipose tissue biopsies were examined for mRNA expression of adipogenic genes, as well as for glucose transporters and inflammatory markers.

In individuals with low-calorie sweetener exposure, the glucose transporter GLUT1 was overexpressed by 2- to 2.2-fold, while the glucose transporter GLUT4 was overexpressed by a factor of 2.7-4.3.

In addition, low-calorie sweetener consumption was associated with up to 2.5-fold overexpression of the sweet taste receptor TAS1R3. Sweet taste receptors are G protein–coupled receptors that are present in taste buds and in other tissues, serving as carbohydrate sensors.

Adipogenic genes were also overexpressed; a 1.5- to 2.4-fold increase was seen in PPARG, for example.

“This expression pattern was most apparent in obese individuals,” the investigators wrote in the abstract accompanying the study, which was presented at the annual meeting of the Endocrine Society.

Further and larger studies are called for, especially in individuals with diabetes and obesity, Dr. Sen said. “However, from our study, we believe that low-calorie sweeteners promote additional fat formation by allowing more glucose to enter the cells, and promote inflammation, which may be more detrimental to obese individuals.”

Dr. Sen and his collaborators reported no relevant disclosures.

koakes@frontlinemedcom.com

On Twitter @karioakes

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