Given that life evolved from food scarce environments, obesity would have been very advantageous in challenging environments where the next meal was not certain. However, this would probably not be a sound survival strategy in hunting and gathering societies where physical fitness was the norm. Obviously, obesity would have been an unachievable goal and probably would not even be an envisioned longshot plan in a meager milieu. However, this article is not about survival in terms of physical fitness to hunt down prey or to run for dear life from the predator. To be clear, I am not suggesting that living with obesity is a choice that emanated from some deliberate plans. If so, therefore would never have been experts promising guaranteed quick weight loss.
Since this article is about thrifty genes discussion, it goes without saying that survival in this context is about cellular response/adaptation to hostile environments. For instance, the Maasai were one of the earliest successful pastoralists and they can digest milk throughout life without losing the milk-digesting enzyme at late childhood. The Intuit, also known as Eskimo, has mutated FADS gene that allow them to tolerate animal fats and resist ketosis due to limited exposure to plant foods in their arctic abode. The Atacamenos who live in Atacama Desert carry a mutated gene called AS3MT that helps them to detoxify arsenic even though the concentration of arsenic in their drinking water can be 20 times higher than the level considered safe for human consumption. The Tibetan plateau, also called the “roof of the world”, is about 3 miles above sea level but through multiple gene variants, Tibetans have thrived in this unusual environment with less than 40 percent oxygen for centuries. Apart from exposure to these pockets of hostile environments with varying cellular and biochemical adaptations, there is a common experience of austere environments by all humans and how we have survived has been a long-standing debate since James Neel proposed the thrifty genes hypothesis in 1962.
Fat, glucose, (found in starch) and proteins may be scarce, but they are available all year round. Probably due to year-round exposure, the metabolic breakdown of glucose is highly regulated. This is evident with excessive consumption of refined glucose causing persistent high levels of glucose in the bloodstream, which is the core disease of type 2 diabetes. It is the reason why people with diabetes would admit that they “cheated last night” when their fasting blood sugar is high the following morning.
However, of all the macronutrients, fructose is the only seasonal nutrient and can only be found plentiful in fruits during summer or rainy season and, unlike grains and tubers, fruits cannot be stored in the natural environments. Since the fruits could not be stored externally in the tents, human bodies have adapted to breaking down fructose exclusively for fat storage. Therefore, the metabolism of fructose is not constrained, a physiological reason why there is no such thing as high blood fructose no matter how much ice cream, fruit juice or cake is consumed. For different reasons outside the scope of this article, organized religion and science tell us that man was primarily frugivorous or fruit eater before he lost the tropical Garden of Eden leading to the dearth of fruits.
The question is how did humans deal with the seasonal scarcity of fructose and what has nitrogen got to do with it? Nitrogen is present in all living organisms, especially in proteins, DNA and in a heterocyclic compound called purine which forms part of the chemical energy called ATP. Biologically, ammonia is the common nitrogenous waste, but it is toxic and takes large amounts of water to maintain concentrations below toxic levels. Notably, tadpoles excrete about 80 percent of nitrogenous wastes as ammonia during the aquatic life, but the enzymes involved in urea production are induced during metamorphosis with gradual transformation from ammonia to urea excretion as they prepare for life on the land. According to a 1995 review, urea requires about 10 times less water than ammonia for excretion.
As water follows salt, it turns out that the challenge of terrestrial life is not just about finding scarce food but includes efficient ways to conserve water. Therefore, humans are sensitive to ammonia as they quickly convert excess amino acids to urea. Interestingly, physical exercise and fasting consume ATP but the body can reconstitute it from the products of its breakdown (ADP and AMP) and from burning fat/glucose in order to sustain the physical exercise and to keep the body alive during fasting. However, consumption of fructose is energy expensive as it degrades ATP very rapidly causing sudden depletion of energy inside the cells with concomitant accumulation of uric acid, an insoluble nitrogenous waste. In most mammals, uric acid is converted to allantoin by uricase and later into urea. However, uric acid is the end product of purines breakdown in man because all humans have nonfunctional or silenced uricase due to mutation of uricase gene.
Ingeniously, uric acid causes “oxidative stress” inside the cell by gumming up the production of ATP, a non-storable chemical energy and directing the process toward fat accumulation through fat production and blocking fat burning. The sudden loss of energy inside the cells also triggers the so-called panic mode to stimulate vasopressin, a hormone for water retention to stave off dehydration and increase hunger, a reason why there is always room for sugary foods or for desserts after the main course.
While the unique breakdown of fructose was meant to store some fat to survive the impending winter or dry season, fructose is now available all year round and we can even produce fructose from grains. Therefore, when a scarce substrate for survival is cheaply available, it can easily turn to a source of indulgence. For instance, each American consumes 60 pounds of sugar per year. High consumption of fructose from refined sugar and other processed foods has been linked to high levels of serum uric acid and gout. Obesity, kidney stones, diabetes type 2, kidney disease, hypertension and non-alcoholic fatty liver disease have been linked to high levels of uric acid. Generally, in metabolism, more is not better.
Just like the Maasai, Intuit, Atacamenos, and Tibetans have adaptively responded to their respective hostile environments, all humans no longer have uricase enzyme, a cellular response to seasonal fructose exposure in the past. Again, do humans have a thrifty gene? To paraphrase Dr. Richard Johnson, a kidney specialist and renowned researcher: Thrifty gene is not a gene we gained, it is the gene we lost. In genetic speaking, all humans are uricase knockout!
Mukaila Kareem, a doctor of physiotherapy and physical activity advocate writes from the U.S.A. and can be reached through makkareem5@gmail.com
