How Food, Movement, and Sunlight Influence Your Biology in Real Time

To illustrate how food, movement, and sunlight affect your internal biology in real time, imagine two individuals having lunch. One eats a meal of steak from a feedlot (grain-fed) cow and French fries, and then choose to watch TV. The other has wild salmon and fresh vegetables and then decides to go for a walk on a sunny day. Our first subject has now melted into the couch and is taking in intermittent segments of a show as he drifts in and out of sleep. The chains of carbohydrates (starch) in the French fries have been broken down into glucose in his small intestine, and the concentration of glucose is rising rapidly in his bloodstream. This triggers the release of insulin from his pancreatic beta cells. The combination of rising blood sugar and insulin release activates three important transcription factors: liver X receptor (LXR), sterol regulatory element-binding protein 1c (SREBP-1c), and carbohydrate response element-binding protein (ChREBP).

From a purely mechanistic standpoint, transcription factors are epigenetic modulators in the most real sense, literally exerting their effect "on top of" DNA by turning up specific genes and turning down others. The three transcription factors bind to designated sites within the DNA called regulatory regions, each factor docking onto a precisely matching regulatory site, where the nucleotides within the grooves of DNA's helical structure fit the molecular architecture of the transcription factors surface like a lock and key. Now, each bound to its designated regulatory site within the genome, the three exert their effect. The regulatory sites, as their name implies, are concentrated in the "promoter" regions of the genes that produce the proteins responsible for setting in motion a series of metabolic processes required to turn the excess blood sugar into fat. The process, termed lipogenesis, takes the excess glucose and, through a series of steps, converts it into four fatty acids: palmitate, stearate, palmitoleate, and oleate. These fatty acids are then incorporated into triglycerides for transport. The triglycerides are then further packaged into fatty particles called very low density lipoproteins (VLDL) and secreted into the bloodstream. Once in the capillaries of adipose tissue (fat tissue) and muscle tissue, the VLDL particles are broken down and can be used in two ways. If our subject was active, the broken-down fat would be taken up preferentially by the muscle tissue and burned for energy in a process called beta-oxidation. However, because he's not active, the majority of the VLDL particles are broken down and repackaged into triglycerides within the adipose cells for long-term energy storage (fat).

Conversely, consider our subject, who ate salmon and vegetables for lunch. After lunch, she notices it's a nice day and decides to go for a walk. The sun begins to warm her skin. Some of the photons penetrate past the skin's outer layers and mingle with a cholesterol-based provitamin circulating in her blood. The energy from the photon converts the provitamin to vitamin D3. The vitamin is then quickly converted to its active form in the liver and kidneys. Once active, the vitamin diffuses into the nuclei of cells and binds with its receptor. The pair then binds to another protein, the retinoic X receptor. The entire complex now acts as a transcription factor and will bind to small sequences of DNA called vitamin D response elements (VDREs), thousands of which have been identified throughout the genome.

As our subject walks, enjoying the warmth of the sun on her skin, hundreds of genes flicker to life, some affecting a range of biological processes that are not immediately obvious: increased calcium absorption, bone development, immune system modulation, and resistance to certain infectious disease, for example. Invigorated by the warmth of the sun and the fresh air, she walks faster. Her muscles began to strain. The proteins from the salmon are digested into individual amino acids. Her straining muscles need fuel, so they absorb glucose and a certain class of amino acids called branched-chain amino acids. The selective displacement of branched-chain amino acids from her bloodstream results in a higher circulating proportion of the amino acid tryptophan. This is significant because only one type of transport protein is capable of shuttling tryptophan through the blood-brain-barrier, and branched-chain amino acids strongly outcompete tryptophan for access to that carrier like thousands of cars trying to cross a single-lane bridge at the same time. But, because she is rapidly burning the branched-chain amino acids, tryptophan is able to diffuse freely into her brain.

She has walked for 10 minutes, and with the sun still spilling onto her skin she's made 20,000 IUs of vitamin D. Her liver has converted much of it to the active form of vitamin D. The activated vitamin D has then gone on to form transcription factors within the nuclei of cells that possess a vitamin D receptor. Ricocheting within the nucleus, the transcription factors eventually bind to VDREs, finally eliciting the upregulation of a vast spectrum of genes. One of the genes that is turned on codes for the enzyme tryptophan hydroxylase 2 (TPH2). TPH2 initiates the conversion of the tryptophan now flooding our subject's brain into the neurotransmitter serotonin, and the concentration of serotonin begins to build within her presynaptic neurons.

Whether serotonin will be released into the neural synapse, where it exerts its effect is influenced by several factors. One is the proportion of certain fatty acids in the bloodstream: Its release is inhibited by the presence in the bloodstream of specific omega-6 fatty acids and facilitated by the presence of marine omega-3 fatty acid eicosapentaenoic acid (EPA). Recall our subject dined on salmon, which is rich in EPA. Another factor is the fluidity of the neural membrane, which determines the mobility of the serotonin receptors that span the neural membrane, floating unanchored like inner tubes on the surface of a lake. Docosahexaenoic acid (DHA), another omega-3 fatty acid, is crucial to neural membrane fluidity; the more DHA in a membrane, the more fluid the membrane is. It is the most abundant fatty acid in the brain, making up 30 percent of the fatty acid content. Serotonin receptors in DHA-rich membranes are supple, less rigid, and bind serotonin more easily much like a well-oiled and pliable baseball glove is able to catch a ball more easily. Salmon also contains DHA.

Between the sunlight, exercise, and the composition of her lunch, an epigenetic chain reaction is set in motion: Sunlight triggers vitamin D synthesis, resulting in the transcription of the serotonin-synthesizing enzyme THP2; exercise promotes tryptophan from the digested salmon to enter the brain; and the fatty acids in the salmon help facilitate the release and uptake of the newly manufactured serotonin.

The edges of her thoughts soften. The anxious, subconscious shadows brighten. She feels a certain weightlessness. The singing of birds and the colors seem more vivid. Without her even realizing it, she thinks happier, more optimistic thoughts. Numerous studies have linked positive emotions to serotonin levels. Serotonin concentrates in the discrete brain regions known to regulate social cognition and decision-making. Collectively, these regions of the brain are called "the social brain." The importance of serotonin's effect on the social brain can be demonstrated by a simple experiment in which subjects are given boluses of branched-chain amino acids. The extremely high concentrations of branched-chain amino acids completely saturate the blood-brain-barrier transport protein, preventing tryptophan from entering the brain, and the subjects' brain serotonin levels plummet. The behavior changes are immediate and obvious. The subjects become more impulsive, aggressive, and experience impaired learning and memory. They have an inability to resist short-term gratification and show difficulty in long-term planning. The results are thought-provoking, especially when considering approximately 70 percent of the world's population has inadequate levels of vitamin D and equally inadequate intake of marine omega-3 fatty acids. On a graver scale, insufficient levels of vitamin D, EPA, or DHA, in combination with certain genetic factors, lead to dysfunctional serotonin activation at key developmental stages in growing children. This confluence of circumstances very likely contributes to serious neuropsychiatric disorders and depression. Serotonin's ability to flush out negative thoughts, encourage positive ones, and trigger a general sense of well-being triggers a cascade of physiological responses that improve one's overall health. 

Cast over a lifetime, negative emotions can exert a powerful effect on longevity. Serotonin's influence goes beyond the occasional good mood. In a classic study, autobiographies written by 22-year-olds were ranked from high to low for positive emotional content. The authors whose autobiographies ranked in the lowest quartile for positive emotions died on average 10 years earlier than those in the highest quartile. It is apparent that seemingly minor decisions, what to eat, how to interact with our environment, even how we choose to perceive the world—all the thoughts and memories that swarm through our minds—have profound effects on our epigenomes through the activation of transcription factors. The inputs are calculated every day. Genes are turned on and turned off moment to moment. The output of this vast and fluctuating algorithm influences our moods, colors our thinking, and governs the innermost workings of our bodies on a molecular level. It influences how active we are, how compulsive, thoughtful, enthusiastic, rational, reclusive, and creative. It affects our abilities, our health and vitality, our susceptibility to specific diseases and disorders, and how we interpret and respond to the world. "Nature," wrote the famous biologist Conrad Waddington, "is more like an artist than an engineer." Indeed, our bodies are unlike any machine. Engineers match form to function, but nature does the same in a way that is so artful in its flexibility, so staggering in its complexity, that it defies the imagination.

Stay strong and curious, and be your own best doctor,

Chuck Meakin MD

Meakin Metabolic Care - Meakin Metabolic Care

Life and Health Coach | Charlotte NC | Coach It Forward Chuck 

Care@HealNavigator.com

Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.