Today’s blog is written by guest blogger, Alden Little, Marketing Intern at Promega.
From genetics to gut microbes, scientists are finding new ways to make white fat act like calorie-burning brown fat. Here’s how three research teams are working to find the next breakthrough obesity treatment.
Rethinking Fat: How New Research is Transforming Obesity Science
Obesity affects millions worldwide and remains a complex challenge shaped by diet, environment, genetics, and socio-economic factors. While medications like semaglutide have shown promise in supporting weight loss, there’s growing interest in alternative strategies.
One area gaining traction is adipose tissue biology. Adipose tissue—commonly known as body fat— is not just a passive storage site for excess energy, but an active player in regulating metabolism and energy balance. Adipose tissue comes in several forms:
- White
- Brown
- Beige
Most of the fat in our bodies is called white adipose tissue (WAT). It stores energy for later use—but too much of it increases the risk for obesity, diabetes, and other health problems. In contrast, brown adipose tissue (BAT) burns energy to generate heat through a process called thermogenesis, helping regulate body weight and temperature. Scientists have discovered a third kind, called beige adipose tissue, which behaves like BAT but can form within WAT under certain conditions like cold exposure or specific molecular triggers.
Turning WAT into beige adipose tissue—a process called “browning”—has gained significant traction as a promising new therapeutic avenue in obesity research. In this post, we look at three recent studies that uncover how genes, microbes, and epigenetic signals influence adipose tissue metabolism and the “browning” phenomenon.
1. How a Mitochondrial Gene Affects Fat-Burning in Human Cells
Study: Huang, M., et al (2023). Identification of a weight loss-associated causal eQTL in MTIF3 and the effects of MTIF3 deficiency on human adipocyte function. eLife, 12, e84168. https://doi.org/10.7554/eLife.84168
Researchers set out to uncover how a gene called MTIF3, known for supporting mitochondrial function influences fat cell metabolism and an individual’s capacity to lose weight. Previous studies had hinted that certain variants of this gene were linked to better outcomes in weight-loss programs, but the underlying biology remained unclear—until now.
In this study, scientists used CRISPR-Cas9 to reduce MTIF3 levels in lab-grown human adipocytes and observed how the cells responded under energy stress conditions, such as glucose restriction, which mimics the effects of dieting. To track metabolic changes, they measured triglyceride storage using the Triglyceride-Glo™ Assay, finding that MTIF3-deficient cells retained more fat when glucose was scarce. They also assessed glycerol release—a marker of lipolysis—using the Glycerol-Glo™ Assay and observed that while these cells could initiate fat breakdown, they failed to burn it efficiently.
These findings shed light on why fat loss can be more difficult for some individuals. It’s not just behavioral—cellular metabolism, influenced by genetics, plays a key role in how adipose tissue behaves, shaping weight-loss outcomes.
2. Gut Bacteria and Cold Temperatures Spark Fat-Burning
Study: Chen, PC., et al (2024). Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning. npj Biofilms Microbiomes 10, 22. https://doi.org/10.1038/s41522-024-00495-8
Can the microbes in your gut influence how efficiently you burn fat? This research team explored how cold exposure alters the gut microbiome in mice—and uncovered a surprising link to fat browning. One bacterium, Marvinbryantia formatexigens, emerged as a key player.
The researchers found that cold temperatures suppress a molecule in the intestine called DUSP6. This reduction leads to increased production of ursodeoxycholic acid (UDCA), a bile acid that encourages the growth of M. formatexigens. In turn, this bacterium produces Nε-methyl-L-lysine, a compound that activates fat browning pathways and reduces fat accumulation.
To examine how these changes influenced gene expression related to fat metabolism, the team first synthesized cDNA using M-MLV Reverse Transcriptase, enabling accurate downstream qPCR analysis. This approach allowed them to pinpoint how cold, microbiota shifts, and bile acid signaling converged to reprogram fat-related gene activity.
This research showcases a new angle for obesity treatment—one that doesn’t target fat tissue directly but instead rewires the microbiome to help the body naturally burn more energy.
3. The Power of Baby Fat: Meet GABPα
Study: Mooli, RGR.,et al (2024). Epigenetically active chromatin in neonatal iWAT reveals GABPα as a potential regulator of beige adipogenesis. Front. Endocrinol. 15:1385811. https://doi.org/10.3389/fendo.2024.1385811
Newborns naturally have higher levels of beige fat to help regulate body temperature. This study explored how that fat develops in infants—and whether it might be possible to reactivate it later in life to support metabolic health.
Researchers identified GABPα, a protein that plays a central role in beige fat formation. It binds to DNA and activates genes involved in glycolysis and thermogenesis, the heat-producing, fat-burning mechanism. To investigate gene activity in beige fat tissue, the team used M-MLV Reverse Transcriptase to generate cDNA for expression analysis. Their findings showed that when GABPα was inhibited, essential thermogenic genes like UCP1 failed to activate, and fat cells lost their calorie-burning capabilities.
This research highlights a third promising strategy for obesity treatment: reawakening the body’s innate thermogenic fat programs that are active in early life but typically fade with age.
Tools That Power Discovery
Targeting adipose tissue directly has emerged as a compelling strategy in the search for new obesity treatments. Unlike approaches that focus solely on appetite or energy intake, targeting fat itself—particularly by enhancing its ability to burn energy—offers the potential for longer-lasting metabolic benefits. However, the question of how to effectively activate and reprogram white adipose tissue remains wide open.
Researchers are approaching this challenge from multiple angles: probing the role of genes in adipocyte metabolism, uncovering how gut microbes influence fat browning, and exploring why beige adipocytes decline with age compared to infancy. Despite the diversity of these studies, they are unified by the tools that make them possible. Promega products support investigations across this entire spectrum of obesity research—whether it’s quantifying metabolic activity in cells or generating high-quality cDNA for gene expression analysis.
Each of these research paths tackles the problem of obesity from a different perspective, yet they converge in their reliance on robust, reliable tools to unlock the complexities of fat biology. That versatility is what makes Promega assays and reagents indispensable in the pursuit of the next generation of obesity therapies.
Looking to explore the molecular pathways of fat metabolism in your lab?
Our portfolio of reporter assays, real time reagents, and metabolic activity kits gives you the power to measure what matters—clearly, accurately, and reliably.
Sources
Chen, PC., et al (2024). Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning. npj Biofilms Microbiomes 10, 22. https://doi.org/10.1038/s41522-024-00495-8
Huang, M., et al (2023). Identification of a weight loss-associated causal eQTL in MTIF3 and the effects of MTIF3 deficiency on human adipocyte function. eLife, 12, e84168. https://doi.org/10.7554/eLife.84168
Mooli, RGR.,et al (2024). Epigenetically active chromatin in neonatal iWAT reveals GABPα as a potential regulator of beige adipogenesis. Front. Endocrinol. 15:1385811. https://doi.org/10.3389/fendo.2024.1385811
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