Genes May Overcome Weight-Loss Plateaus

---

One of the most challenging obstacles in weight loss is a phenomenon called the metabolic plateau. This occurs when the body, in response to reduced calorie intake, slows its metabolism as a natural survival mechanism aimed at conserving energy. While this response is designed to protect us during periods of low food availability, it often works against those trying to shed excess weight.

Danish scientists recently pinpointed a gene known as plasmalemma vesicle-associated protein (PLVAP or PV-1), which plays a key role in regulating how the liver processes energy. Under normal conditions, the liver switches from burning carbohydrates to fat oxidation. But this study found that by deactivating the PV-1 gene in mice, the liver was “tricked” into continuing to burn carbs when fasting.

These findings have sparked new hope for developing innovative treatments that not only address weight-loss challenges but also improve overall metabolic function. Researchers believe this breakthrough may also amplify the effectiveness of existing weight-loss medications by preventing the loss of effectiveness that often accompanies slowed metabolic processes. 

NOTE: The University of Southern Denmark’s PV-1 study on metabolism was initially published in the journal Cell Metabolism. The team of research scientists included Daniel Hansen, Jasmin Jensen, Christian Andersen, Peter Jakobsgaard, Jesper Havelund, Line Lauritsen, Samuel Mandacaru, Majken Siersbæk, Oliver Shackleton, Jonathan Brewer, Blagoy Blagoev, Nils Færgeman, and Kim Ravnskjær (all from SDU). Collaborators from Japan, the USA, and Finland. Danish scientists suggest that targeting the PLVAP gene could be key to overcoming common barriers by offering new hope for those with significant weight-loss goals.

How Cells Trigger Metabolic Changes

The research on PLVAP gene at the University of Southern Denmark revealed insights that could reshape how we approach weight-loss plateaus going forward. PV-1 located in liver stellate cells help regulate the body’s metabolic shifting during fasting or periods of reduced daily food intake. Normally, during calorie restriction or fasting, the liver transitions energy sources from burning sugar (carbohydrates) to fat oxidation that produces ketone bodies in the process.

However, when plasmalemma vesicle-associated protein was deactivated in mice, the metabolic shift was stalled and prevented both fat burning and ketone creation. Instead, fatty acids were rerouted from the liver to skeletal muscles, allowing the liver to continue burning sugar and without any adverse effects to the mice. Manipulating this essential mechanism offers exciting possibilities for treating the metabolic resistance that causes those dreaded weight-loss plateaus.

By understanding how the PLVAP gene goes about doing its job, researchers believe these initial findings highlight the potential for managing other metabolic issues, such as type 2 diabetes, insulin sensitivity, and fatty liver disease. While more human studies are needed, these findings open exciting new pathways for creating therapeutic solutions that address challenges of metabolic resistance and improve the individual’s overall metabolic health.

Kickstart Your Journey for Weight Control

Weight loss medications, originally developed to treat diabetes, have emerged as a groundbreaking option for individuals seeking effective weight management solutions. These medications work by mimicking the glucagon-like peptide-1 hormone, helping to regulate blood sugar levels, curb appetite, and promote feelings of fullness. By slowing gastric emptying and reducing between-meal snacking, treatments make it easier to maintain a calorie deficit without constant hunger and achieve sustainable weight loss.

Since individuals who qualify for prescriptive medical weight loss treatments can still encounter metabolic slowdowns, combining them with therapies targeting the PLVAP gene may provide a more effective approach to sustaining weight loss for the long haul. After all, excessive calorie restriction often forces the body into “starvation mode,” where fat oxidation occurs. Moreover, the liver is a key metabolic organ that plays a critical role in the energy shifting process once glycogen stores are depleted.

At Metabolic Research Center, we combine over three decades of weight management expertise with the latest innovations, including prescription weight loss programs. Visit us at the medical weight management clinic Champagne-Urbana to see how our experienced team can help you achieve your goals. All it takes is a quick email or call to learn more about MRC’s science-backed weight loss programs. But, don’t forget to schedule a free consultation as your first step toward metabolic well-being.