{"id":569116,"date":"2026-05-06T11:13:13","date_gmt":"2026-05-06T11:13:13","guid":{"rendered":"https:\/\/www.newsbeep.com\/uk\/569116\/"},"modified":"2026-05-06T11:13:13","modified_gmt":"2026-05-06T11:13:13","slug":"new-drug-melts-fat-even-on-a-high-fat-high-sugar-diet","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/uk\/569116\/","title":{"rendered":"New Drug Melts Fat Even on a High-Fat, High-Sugar Diet"},"content":{"rendered":"

\"Weight<\/a>Researchers have identified a small-molecule compound that alters how cells handle energy, producing striking metabolic effects in mice exposed to a long-term high-fat, high-sugar diet. Credit: Stock<\/p>\n

Researchers have identified a small-molecule compound that appears to counteract weight gain and metabolic damage in mice exposed to a long-term Western diet.<\/p>\n

A drug candidate developed by researchers at The University of Texas Health Science Center at San Antonio<\/a> kept mice from becoming obese even after long-term exposure to a sugar-rich, fat-heavy Western diet. The treatment also protected the animals from liver damage linked to poor diet, including fatty buildup and tumor formation.<\/p>\n

The work points to an unexpected target: magnesium movement inside mitochondria, the energy-producing structures found in cells.<\/p>\n

\u201cWhen we give this drug to the mice for a short time, they start losing weight. They all become slim,\u201d said Madesh Muniswamy, PhD, a professor of medicine at the Joe R. and Teresa Lozano Long School of Medicine.<\/p>\n

The findings were published in Cell Reports. Muniswamy, director of the Center for Mitochondrial Medicine at UT Health San Antonio, was the study\u2019s senior author. The research also included scientists from the University of Pennsylvania and Cornell University.<\/p>\n

Why Magnesium Became the Focus<\/p>\n

Magnesium is essential for life. It helps regulate blood sugar and blood pressure, supports bone health, and participates in many chemical reactions that keep cells running. It is also the fourth most abundant element in the body, behind calcium, potassium, and sodium.<\/p>\n

But inside mitochondria, the study suggests, too much magnesium may act less like fuel and more like a brake. When magnesium enters mitochondria through a channel controlled by a gene called MRS2, it can slow the cell\u2019s ability to burn sugar and fat efficiently.<\/p>\n

\"Mitochondria<\/a>Mitochondria are specialized structures inside cells that convert nutrients into usable energy. Often called the cell\u2019s \u201cpowerhouses,\u201d they produce ATP, the molecule that fuels many cellular processes. Credit: Shutterstock<\/p>\n

\u201cIt puts the brake on, it just slows down,\u201d said co-lead author Travis R. Madaris, a doctoral student in Muniswamy\u2019s lab.<\/p>\n

To test the idea, researchers removed the MRS2 gene in mice and fed them a Western diet for as long as 52 weeks. Normal mice gained weight and developed signs of metabolic disease. Mice without MRS2 stayed lean, despite eating similar amounts of food, drinking similar amounts of water, and moving about as much as the other animals.<\/p>\n

Their metabolism also appeared more active. The mice were better able to use sugar and fat for energy, and their white fat began showing signs of \u201cbrowning,\u201d a shift toward a more energy-burning type of fat.<\/p>\n

\"Stepping<\/a>Magnesium acts like a brake on energy production, researchers found. Credit: ShutterstockProtection Beyond Body Weight<\/p>\n

The liver results were especially dramatic. In typical mice, the Western diet led to fatty liver changes, fibrosis, liver enlargement, and frequent liver tumors. Those problems were largely absent in mice lacking MRS2.<\/p>\n

Their liver and adipose (fat) tissues showed no evidence of fatty liver disease, a condition closely tied to obesity, type 2 diabetes, and poor diet. The animals also maintained healthier blood glucose levels and avoided several signs of diet-induced metabolic syndrome.<\/p>\n

The researchers found that reducing magnesium entry into mitochondria changed how cells handled citrate, a molecule used to make fat. With less mitochondrial magnesium, less citrate appeared to leave the mitochondria for fat production. That shift may help explain why the mice accumulated less fat in the liver and body.<\/p>\n

A Drug That Copies the Genetic Effect<\/p>\n

The team then tested a compound called CPACC, which blocks magnesium transport through the same mitochondrial pathway. UT Health San Antonio has filed a patent application for the drug.<\/p>\n

In experiments, CPACC reduced lipid buildup in liver cells, increased mitochondrial respiration, lowered plasma citrate, and promoted features of beige fat, a more metabolically active form of fat. In mice on a high-fat diet, injections of CPACC every three days for six weeks limited weight gain and improved a marker of liver function.<\/p>\n

\"Mitochondria<\/a>Microscopic image of mitochondria within a single heart cell. Mitochondria highlighted in red were exposed to ultraviolet light. Credit: National Heart, Lung and Blood Institute, National Institutes of Health<\/p>\n

\u201cLowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress,\u201d said co-lead author Manigandan Venkatesan, PhD, a postdoctoral fellow in the Muniswamy lab.<\/p>\n

Madaris said the collaboration was essential to developing the compound. Joseph A. Baur, PhD, of the University of Pennsylvania, and Justin J. Wilson, PhD, of Cornell University, were among the contributors. \u201cWe came up with the small molecule and Justin synthesized it,\u201d Madaris said.<\/p>\n

What This Could Mean for Future Treatments<\/p>\n

The results suggest that mitochondrial magnesium channels may be a promising target for obesity, fatty liver disease, type 2 diabetes, and other cardiometabolic conditions. Still, the findings are early. The main experiments were done in mice, and the study used a global MRS2 knockout, which means the researchers could not isolate the role of the channel in each individual tissue. The authors also note that future work will need safer, more refined MRS2 modulators suitable for human studies.<\/p>\n

\u201cThese findings are the result of several years of work,\u201d Muniswamy said. \u201cA 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.\u201d<\/p>\n

Follow-Up Research<\/p>\n

Related studies published after the CPACC work suggest that mitochondrial magnesium transport may matter beyond obesity and fatty liver disease.<\/p>\n

In a 2024 Mitochondrion study, researchers showed that lower magnesium levels inside mitochondria increased activity of the mitochondrial calcium uniporter (MCU), which controls calcium uptake into mitochondria. The finding helps explain how mitochondrial magnesium can influence calcium signaling, energy production, and cell stress.<\/p>\n

In 2026, a Hypertension study connected Mrs2 to pulmonary arterial hypertension (PAH). In diseased pulmonary artery cells, excess mitochondrial magnesium helped drive metabolic dysfunction, lactate buildup, calcium overload, mitochondrial damage, and abnormal cell growth. Reducing Mrs2 activity improved mitochondrial function and eased vascular remodeling in rats.<\/p>\n

References:<\/p>\n

\u201cLimiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress\u201d by Travis R. Madaris, Manigandan Venkatesan, Soumya Maity, Miriam C. Stein, Neelanjan Vishnu, Mridula K. Venkateswaran, James G. Davis, Karthik Ramachandran, Sukanthathulse Uthayabalan, Cristel Allen, Ayodeji Osidele, Kristen Stanley, Nicholas P. Bigham, Terry M. Bakewell, Melanie Narkunan, Amy Le, Varsha Karanam, Kang Li, Aum Mhapankar, Luke Norton, Jean Ross, M. Imran Aslam, W. Brian Reeves, Brij B. Singh, Jeffrey Caplan, Justin J. Wilson, Peter B. Stathopulos, Joseph A. Baur and Muniswamy Madesh, 27 February 2023, Cell Reports.
DOI: 10.1016\/j.celrep.2023.112155<\/a><\/p>\n

\u201cMrs2-mediated mitochondrial magnesium uptake is essential for the regulation of MCU-mediated mitochondrial Ca2+ uptake and viability\u201d by Thiruvelselvan Ponnusamy, Prema Velusamy and Santhanam Shanmughapriya, 8 April 2024, Mitochondrion.
DOI: 10.1016\/j.mito.2024.101877<\/a><\/p>\n

\u201cEnhanced Mitochondrial Mrs2-Mg2+ Signaling Drives Mitochondrial Dysfunction in Pulmonary Arterial Hypertension Rats\u201d by Ruo-Nan Chen, Xue-Qin Weng, Yan Yan, Qin-Ye Chen, Yi-Chen Lin, Lan Liu, Xiao-Ling Zhuang, Long-Xin Gui, James S.K. Sham, Mo-Jun Lin and Da-Cen Lin, 16 March 2026, Hypertension.
DOI: 10.1161\/HYPERTENSIONAHA.126.25866<\/a><\/p>\n

Never miss a breakthrough: Join the SciTechDaily newsletter.<\/a>
Follow us on Google<\/a> and Google News<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"Researchers have identified a small-molecule compound that alters how cells handle energy, producing striking metabolic effects in mice…\n","protected":false},"author":2,"featured_media":569117,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[59,102,1989,30992,236,56,54,55,194882,4405],"class_list":["post-569116","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-gb","tag-health","tag-liver","tag-mitochondria","tag-obesity","tag-uk","tag-united-kingdom","tag-unitedkingdom","tag-university-of-texas-at-san-antonio","tag-weight-loss"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/posts\/569116","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/comments?post=569116"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/posts\/569116\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/media\/569117"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/media?parent=569116"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/categories?post=569116"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/tags?post=569116"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}