The sugar coated truth of artificial sweeteners

Previous studies have suggested that consuming artificial sweeteners may cause overindulgence and pack on extra pounds. New research published in Cell Metabolism reveals the mechanism behind this counterintuitive effect.

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Credit: Pixabay

Artificial sweeteners made their foray into the market with the intention of combatting the increasing rate of obesity. Researchers from University of Sydney’s Charles Perkins Centre have observed that consumption of synthetic sweeteners may actually interfere with our learned responses and innate ability to balance glucose and energy levels.

The sweet imbalance 

Our body has the ability to gauge how many calories we need, partially based on the sweetness of food. The richer it is in sweetness, the higher it is in calories and our brain can tell us when to stop eating. Artificial sweeteners puts a wrench in this whole process. These are synthetic sweeteners, many times sweeter than regular sugar and most of them have no calories. Thus, you would only need a fraction, compared with the amount of sugar required to sweeten your tea. Sounds appealing right? Well, not really…In a classic case of a solution worsening the problem, consuming artificial sweeteners made people feel hungrier and actually motivated them to eat more!

When the brain realises there is an imbalance between the sweetness of food and its caloric content, it triggers a fasting state, which leads to hunger pangs. It would end up recalibrating the whole system , and if originally 3 meatballs were enough, now your body will need more, say 5 meatballs to satiate your hunger.

Slide2      Credit: Modified from Pixabay

Mechanism

Fruit flies possess systems that assess both sweetness and caloric content of food and have conserved insulin and gustatory reward pathways, making them an ideal model to dissect the mechanism. Fruit flies fed with a sucralose diet (compared to a control group with sucrose diet) for more than 5 days, exhibit an increased food intake along with other physiological responses such as hyperactivity and reduced total sleep. Though this effect has been documented in humans and mice in previous studies, this team led by Associate Professor Greg Neely from the University of Sydney’s Faculty of Science has shed light on the hitherto unknown mechanism behind this response.

They found insulin receptors being upregulated after 4 days of sucralose diet, via RNA-Seq. Knockdown studies of this receptor in fruit flies showed that they no longer showed an increase in appetite. Moreover, activating the insulin-producing cells was found to be sufficient to increase the food intake, which persists even in the absence of sucralose, hinting on how artificial sweeteners hack the system.

The brain’s gustatory reward pathway conserved from invertebrates such as Drosophila through to mammals, perceives ‘sweetness’ as a means to predict the nutritional value of food. On receiving a synthetically sweetened diet, the sensory sweetness of food does not match the caloric content for a sustained period, triggering a compensatory response that alters taste sensitivity and increases motivation to eat.

Sustained sucralose ingestion activates a conserved neural fasting response. This response integrates pathways that govern feeding, gustatory reward, and energy sensing that together modify how sweet food is perceived.

“Using this response to artificially sweetened diets, we were able to functionally map a new neuronal network that balances food’s palatability with energy content. The pathway we discovered is part of a conserved starvation response that actually makes nutritious food taste better when you are starving,” said Associate Professor Neely.

However, it remains to be seen whether additional factors in mammals, such as a wider diversity of gut microbial flora interact with the overall physiology or regulation of energy homeostasis.

Original paper can be accessed here: Cell Metabolism

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