Magic drug prevents weight gain in mice living on a sugary diet

What’s more surprising is that the mice were fed a high-fat and sugar-rich diet throughout their lives, and still, when exposed to CPACC, these subjects turned slim and healthy.  

The link between obesity and magnesium

The answer to this question lies in our body’s cellular mechanism. Our body is full of elements such as sodium, calcium, magnesium, and potassium, and each of these elements plays an important role in ensuring healthy metabolism. 

For example, while calcium makes our bones stronger, magnesium keeps our blood sugar in control and facilitates protein production. However, an overdose of any such element in our body could also cause disturb our body’s metabolism. 

While looking for factors responsible for weight gain on a cellular level in mammals, the study authors noticed that at times when body cells received more than the required amount of magnesium, the energy production in cells slowed down.

They suggest that excessive magnesium disturbs mitochondria activity in body cells and leads to the deposition of excessive fat in the body. This extra fat increases weight and eventually becomes the cause of liver and heart diseases.  

How does CPACC work?

When CPACC was administered to mice who were living on an unhealthy western diet, the subjects started losing weight and became slim. Plus, their livers stopped getting adversely affected by their sugary diets, reducing the risk of liver or heart problems in mice to a large extent.

“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,” said Madesh Muiswamy, study author and professor of medicine at UT Health San Antonio. 

CPACC achieved this by deleting a gene named MRS2 which is responsible for transporting magnesium to mitochondria in body cells. As the drug inhibited MRS2 activity, energy production in mice cells increased. This further allowed the cells to do fat and sugar metabolism more efficiently. 

One of the lead authors and a researcher at UT Health San Antonio, Manigandan Venkatesan, said, “Lowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress.” 

The researchers are eager to continue researching the impacts of CPACC in light of these findings. Hopefully, one day this drug will play an important role in overcoming obesity and its detrimental effects on humans.  

The study is published in the journal Cell Reports.

Study Abstract:

The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-μM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but the physiological significance of this competition remains elusive. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, β-oxidation, thermogenesis, and HIF-1α-targets, in Mrs2−/− mice that are further enhanced under Western-diet-associated metabolic stress. Thus, lowering mMg2+ promotes metabolism and dampens diet-induced obesity and metabolic syndrome.