Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts

Abstract

Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous–Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12–14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high‐fructose corn syrup is driving ‘burden of life style’ diseases, including obesity, diabetes and high blood pressure.

Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer’s Disease

“…Fructose, either from the diet or endogenously produced, is used by many species to aid survival (Johnson et al, 2020). Of interest, mutations that could enhance this pathway have occurred in various species, including humans (Johnson and Andrews, 2015).…”

Biomimetics – Nature's roadmap to insights and solutions for burden of lifestyle diseases

“…Contained within these countless adaptations, evolved over hundreds of millions of years may be strategies with salience for human health. Our bodies possess limited physiologic responses to short periods of hypoxia, dehydration, starvation, infections and trauma . However, amongst the millions of other species on Earth facing the same challenges, we find countless other strategies (adaptations).…”

“…To fully understand the underlying causes of the cluster of burden of lifestyle diseases, medical researchers should take advantage the possibility to learn from nature and the dramatic changes that occurred during evolution. As an example, two mutations (the blockade of vitamin C synthesis and silencing of the uricase gene) that occurred during periods of mass extinction may have had major effects on the current panorama of burden of lifestyle diseases since these mutations enhanced the activity of fructose to generate fat and, thus, predispose modern sedentary man to fat mass accumulation and metabolic diseases .…”

“…They survive by down‐regulating their mitochondrial function and living in a glycolytic state, which allows them to reduce their oxygen demands. One of the ways this happens is by the production of fructose as its metabolism helps shift the animal to a glycolytic state . Since hypoxia causes a oxidative stress, this rat handles this aspect by markedly increasing its antioxidant systems, based on upregulation of Nrf2‐KEAP1 .…”

“…Unlike engineering, material sciences and product design, the field of medicine is only beginning to leverage the power of biomimetics to accelerate biomedical innovation and find novel approaches to fight human diseases. To enable the coexistence of humans, animals and plants on a planet that face many problems such as global warming, pollution and shortage of water , we believe biomimetics will be a field increasingly in demand since it has the potential to provide many answers.…”