Too Little Water Makes You Fat – Researchers Discover a Connection

According to the researchers, these findings provide important insights into better understanding obesity and overweight in humans. The observation that water deficiency can act as a stimulus for fat storage during hibernation is significant for human obesity, particularly in response to salt and sugar intake. Adequate hydration could therefore have a protective effect. Additionally, the study sheds light on how glucagon-like peptide-1 agonists can lead to weight loss.

In their newly published study, the researchers analyze the biological mechanisms animals use to prevent dehydration – an important One Health topic for both animals and humans, especially in the context of rising temperatures and water scarcity. Fat and glycogen produce water during metabolism, which can serve as a water source for various animals. In hibernating animals, this process works as follows: In autumn, fat production is stimulated by a vasopressin-dependent, carbohydrate-based metabolism. This leads to thirst, increased water intake, and the storage of glycogen and fat. As autumn progresses, animals switch to a fat-based metabolism as vasopressin levels decrease, potentially triggering the onset of hibernation – a period when water is no longer available.

During Hibernation: Water Production from Fat

Once hibernation begins, metabolic water is produced through fat metabolism, while vasopressin secretion is suppressed and serum osmolality decreases, which in turn suppresses thirst. According to study co-author Johanna Painer-Gigler from FIWI at Vetmeduni: "We suspect that water production from fat cannot keep up with demand, and respiratory acidosis develops as a result of hypoventilation. This necessitates waking up during hibernation. These interbout arousals (IBA), during which the animal warms itself up by switching to carbohydrate metabolism, result in a rapid increase in water availability from glycogen breakdown, facilitating the ventilation required to correct acidemia. The animal then lowers its metabolism again, allowing the fat-based metabolism of hibernation to continue."

Adequate Water as Protection Against Obesity in Humans?

The observation that obesity serves a natural purpose – namely survival, particularly through water storage during times of scarcity – could be significant for understanding human obesity. Since humans generally regulate their weight well, there is likely some form of dysregulation that triggers fat storage. "Our research suggests that both dietary fructose and endogenous fructose drive this dysregulation by altering leptin signaling. Furthermore, fructose promotes vasopressin production and thirst, a process further stimulated by salt intake," explains study co-author Szilvia Kalgeropoulu from FIWI.

It is therefore unsurprising that most people with obesity exhibit elevated vasopressin levels in their blood and show signs of dehydration, such as increased serum osmolality. According to the researchers, such elevated serum osmolality is a strong predictor of metabolic diseases, while adequate hydration can lower copeptin levels and plasma glucagon levels.

Climate Change, Water Scarcity, Obesity, and Peptide-1 Agonists

Maintaining adequate hydration in a changing, warming climate appears to be crucial for good health. In fact, individuals who appear clinically well-hydrated but maintain their normal water balance primarily through vasopressin stimulation and other water-saving mechanisms may have an increased risk of obesity and metabolic diseases. "In this context, the effectiveness of glucagon-like peptide-1 agonists in reducing obesity may partly be due to their known ability to inhibit vasopressin and glucagon production," emphasize Johanna Painer-Gigler and Szilvia Kalgeropoulu. The research team works interdisciplinarily, consisting of human medicine experts, veterinary scientists, and biologists, collaborating on a biomimetic approach.

 

The article „Water scarcity and conservation and their role in obesity in nature and in humans“ by Richard J. Johnson, Johanna Painer-Gigler, Szilvia Kalgeropoulu, Sylvain Giroud, Paul G. Shiels, Mehmet Kanbay, Ana Andres-Hernando, Bernardo Rodriguez-Iturbe, Miguel A. Lanaspa, Peter Stenvinkel and Laura G. Sánchez-Lozada was published in „Journal of Internal Medicine“ .


Scientific article



Scientific contact:
Dr. Johanna Painer-Gigler
Forschungsinstitut für Wildtierkunde und Ökologie
Veterinärmedizinische Universität Wien (Vetmeduni)
Johanna.Painer@vetmeduni.ac.at