“Fasting + Ozempic/Wegovy + no tasty food near me”
Fasting + Ozempic/Wegovy + no tasty food near me
— Elon Musk (@elonmusk) November 16, 2022
Elon Musk posted this simple formula on his X account that helped him lose 30 lbs. Novo Nordisk originally designed Ozempic to treat diabetes, but its weight-loss effects began to attract more attention. Now, scientists at Stanford Medicine have identified a naturally occurring molecule that mimics some of the weight-loss effects of semaglutide, the active ingredient in Ozempic. The natural alternative reduced appetite and body weight in animal studies, without side effects like nausea, bloating, constipation, and muscle loss associated with Ozempic.
The molecule known as BRP activates distinct groups of neurons in the brain, offering a highly precise way of controlling appetite and metabolism. BRP acts through a pathway related to, but not the same, as Ozempic, that targets receptors in both the brain and gut. That’s why Ozempic slows the movement of food through the digestive tract and lowers blood sugar levels. In contrast, BRP solely acts on the hypothalamus, which controls hunger and fullness.
How did A.I. help in the Discovery?
Artificial intelligence helped the researchers sort through a large group of molecules known as prohormones. These molecules are inactive but can be cut into smaller fragments called peptides, which can act as hormones and influence processes such as metabolism.
Prohormones can be split in many ways, producing multiple useful peptide hormones. However, using traditional lab methods to identify those is quite challenging. Researchers have a hard time filtering out these rare signaling molecules from the inactive fragments created during protein breakdown.
To narrow the search, the team focused on prohormone convertase 1/3, an enzyme associated with obesity that cleaves proteins at specific sites. GLP-1 or glucagon-like peptide 1 is a product of this enzyme, which regulates appetite and blood sugar. Semaglutide mimics GLP-1, regulating appetite and helping with weight loss.
Instead of using traditional protein analysis techniques, the researchers developed a software called Peptide Predictor. This algorithm scanned all 20,000 human protein-coding genes to identify sites where prohormones can be cleaved into peptides. Hormones are proteins secreted outside cells and have multiple cleavage points. The research team narrowed down to these proteins, resulting in 373 prohormones suitable for further testing.
The Star of the Show
From these proteins, the algorithm predicted 2,683 possible peptides, of which 100 were selected, including GLP-1, and their effects on lab-grown brain cells were tested. As expected, GLP-1 boosted neuron activity. However, BRP, a smaller peptide made up of just 12 amino acids, stole the spotlight with an even stronger response. It increased neuronal activity by 10x. When tested in lean mice and minipigs, whose metabolic and feeding patterns parallel those of humans, BRP significantly reduced food intake—a single dose before feeding lowered consumption by half within an hour.
In obese mice, daily injections over two weeks led to an average weight loss of 3 grams, primarily fat, whereas untreated mice gained about 3 grams during the same period. The treated animals also displayed better glucose and insulin tolerance. More importantly, the animals didn’t show changes in movement, water intake, and digestion, or signs of anxiety. Additional analyses confirmed that BRP acts through distinct pathways from GLP-1 or semaglutide.
A More Focused Approach to Weight Loss
The research team is working to identify the specific receptors that BRP interacts with to understand better how it acts in our bodies. “The lack of effective drugs to treat obesity in humans has been a problem for decades,” assistant professor of pathology Katrin Svensson, PhD, said. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if it is safe and effective in humans.”
The Hype Around Ozempic
Novo Nordisk’s patent on Ozempic expires this year in many countries, like India and China. Experts predict that this will flood the markets with generic, low-cost alternatives priced at half or less of the current versions. While this will make the medicine more accessible for diabetics, it comes with the risk of off-label use to reduce weight just for aesthetic purposes.
#Ozempic has over 600 million views on TikTok, and many influencers have spread misinformation by suggesting that laxatives are a ‘budget Ozempic’. Berberine, a compound referred to as ‘nature’s Ozempic,’ set the trend as a cheaper option. In fact, the craze fuelled a whole black market selling fake and counterfeit Ozempic products.
The hype eventually caused a global shortage, and with patents expiring, unfair use will skyrocket. Ozempic is neither a miracle cure nor a quick fix; losing weight requires a consistent and healthy lifestyle. Wegovy, on the other hand, is a similar semaglutide drug specifically prescribed for weight loss, but must be used with proper medical supervision.
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