New weight loss drug tackles the Western diet and lets you eat anything

Researchers at UT Health San Antonio have identified a small-molecule drug that might just be the answer to the obesity epidemic fueled by the Western diet. 

The study promises an intervention that prevents weight gain and counters adverse liver changes typically observed in mice fed a high-sugar, high-fat diet.

Study senior author Dr. Madesh Muniswamy is a professor of medicine at UT Health San Antonio’s Joe R. and Teresa Lozano Long School of Medicine. “When we give this drug to the mice for a short time, they start losing weight. They all become slim,” said Dr. Muniswamy.

How to lose weight on a Western diet

On a cellular level, the scientists focused on the role of magnesium in metabolism. A vital element, magnesium is crucial for various physiological processes, such as blood sugar and blood pressure regulation and bone development. 

Its significance is underscored by its abundance in the human body, ranking fourth among cations after calcium, potassium, and sodium.

However, it was discovered that an excess of magnesium dampens the energy production processes within the mitochondria – often dubbed the cells’ powerhouses. 

“It puts the brake on, it just slows down,” explained study co-lead author Travis R. Madaris, a doctoral student in the Muniswamy laboratory.

What the researchers discovered 

The team found that the removal of the MRS2 gene, responsible for ferrying magnesium into the mitochondria, optimized the metabolism of sugar and fat in these cellular power plants. 

The practical implications? Mice that were not only slim but also exhibited healthier liver and adipose tissues, free from fatty liver disease indications commonly associated with poor diets, obesity, and type 2 diabetes.

Building on this finding, the researchers formulated a drug, named CPACC, designed to mimic the effect by limiting magnesium’s entry into the mitochondria. 

The drug’s efficacy mirrored the gene deletion, producing slender, healthy mice. Recognizing its potential, UT Health San Antonio has initiated the patenting process for CPACC.

Long-term dietary stress 

But why focus on mice? The rodents served as a vital surrogate for the long-term dietary stress humans undergo due to the calorific, sugar-laden, and fatty nature of the Western diet. 

This kind of diet is all too often linked to major health issues, including obesity, type 2 diabetes, and cardiovascular diseases. 

“Lowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress,” noted Dr. Manigandan Venkatesan.

The multi-institutional collaboration also drew insights from Dr. Joseph A. Baur of the University of Pennsylvania and Dr. Justin J. Wilson of Cornell. “We came up with the small molecule and Justin synthesized it,” said Madaris.

“These findings are the result of several years of work,” said Dr. Muniswamy. “A drug that can reduce the risk of cardiometabolic diseases such as heart attack and stroke, and also reduce the incidence of liver cancer, which can follow fatty liver disease, will make a huge impact. We will continue its development.”

The study is published in the journal Cell Reports.

More about the Western diet

The Western diet, a dietary pattern that has become increasingly common in developed countries, is characterized by high intakes of red and processed meats, sugary beverages, high-fat dairy products, and refined grains. It’s often contrasted with diets that emphasize whole grains, fruits, vegetables, lean proteins, and healthy fats, such as the Mediterranean diet.

One of the most striking features of the Western diet is its heavy reliance on processed and convenience foods, often loaded with added sugars, unhealthy fats, and sodium. These attributes contribute to its palatability and the addictive quality that often leads to overconsumption.

Health consequences

Numerous studies have linked the Western diet to a range of health problems. Its high saturated fat content has been associated with elevated levels of LDL cholesterol, a risk factor for heart disease and stroke. Additionally, the high sugar content often leads to spikes in blood sugar levels, contributing to the development of type 2 diabetes.

The lack of fiber, found in whole grains and fresh fruits and vegetables, can lead to digestive problems, while the abundance of red and processed meats has been associated with an increased risk of certain types of cancer.

The obesity connection

The Western diet is frequently implicated in the obesity epidemic, particularly in the United States and other Western countries. The abundance of high-calorie, low-nutrient foods encourages overeating, leading to weight gain and obesity.

The obesity crisis, in turn, contributes to a host of other health problems, such as metabolic syndrome, a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes.

Social and cultural factors

The prevalence of the Western diet is not solely a matter of individual choice. Marketing, availability, and the relatively low cost of processed foods have contributed to its widespread adoption. 

Social and cultural norms, along with economic factors, play a role in shaping dietary patterns, making the shift away from the Western diet a complex public health challenge.

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