Updated: Nov 18, 2020
Why your stomach is full but your brain is starving.
By Drew Edwards, EdD, MS and Sean C. Orr, M.D.
July 3, 2020
This is the first installment in a three-part series about brain function and its relationship to body weight.
Obesity and Misperception
Genetics, sedentary lifestyle, and poor dietary habits have conspired to make millions of Americans obese. In spite of emerging evidence that obesity is, in fact, a serious metabolic disease, overweight and obese persons are too often viewed as slothful, and lazy, reminded by every magazine cover that they are unacceptable in today's looks-are-everything world. In spite of the ubiquity of overweight and obese persons in north America, the airbrushed, a photoshopped and surgically enhanced standard of beauty has been foisted upon us. As we well know, now, it frankly is impossible to attain such a standard naturally, as the proliferation of the beauty and cosmetic surgery industry has shown us.
Indeed, our perceptions have been hijacked by a ravenous industry. As a result, millions of teens and young adults, and females in particular, believe their worth is determined by their dress size, cup size, waistline, you name it. For a while, we had erroneously assumed that the primary consumers of cosmetic intervention were baby boomers and middle-aged persons -- from botox, liposuction, expensive fillers, microneedling, microblading (tattooing eyebrows, eyeliner, hairlines) and of course breast and buttock augmentation, and a plethora of cosmetic dentistry. We were wrong, so wrong. The fastest growing age cohort for these services are women and men in their 20’s and 30’s.
It makes sense now. We wrote a paper over 8 years ago commenting on (or more accurately, lamenting) the new data revealing that 70-80 percent of teenage girls ”hate” the way they look. Concurrently, the CDC had placed a new cohort of high-risk females on their monitoring schedule for suicide. Sadly, this new high-risk cohort comprised 10-14 year-old-girls! Why? Because the suicide rate for these children had more than tripled in just two years. We’ve been doing this a long time but we never thought we’d see the day when a little girl, 10 years old, would wake-up and not find a single reason to go on living. What kind of Hell is she perceiving that death is the best alternative in her mind?
In response to the fat shaming and stigma that is alive and kicking - hard - a recent social movement has emerged with the noble intention of counteracting this trend. Unfortunately, this movement, aimed at attaining acceptance, has backfired. It now edifies and celebrates obesity, a serious, chronic, and poorly understood life-threatening condition associated with metabolic derangement and which includes, but is not limited to:
Type 2 diabetes
Depression, Anhedonia, Dysthymic Disorder and Suicidality
Obesity is now endemic (an expected outcome) in the US. However, it is one thing to accept a person who is obese without judgement or malice. It is an entirely different thing to normalize, even celebrate, a chronic, life-threatening endemic disorder.
Accordingly, obesity and its comorbid conditions have overwhelmed our medical system, and the annual cost is now incalculable due to direct and indirect healthcare costs and lost economic productivity. Fortunately, hard science over the past several decades has shed some much needed light on the cause and pathophysiology of this confounding condition, and we aim to distill some of those concepts in this series in a way that is practical and applicable.
Clearly, no one would choose to become obese any more than one would choose to have cancer. Obesity and its cardiometabolic and neuropsychiatric comorbidities are heartbreaking conditions that happen to good people in spite of the cruel stereotyping that is still rampant in our culture. Like most chronic conditions, research has brought to light the interplay between genetic, familial, and environmental risk factors that combine to result in obesity. Let’s first examine the “thrifty system” of the body and how it’s helped to keep our species alive for so long.
Anthropologically speaking, North Americans evolved from eating fresh vegetation and lean game, which had to be found, gathered, planted, harvested, hunted, killed and dragged home---to hunting and gathering in convenience stores and drive-through windows. Our ancestors did not require gym memberships to sweat out excess calories, nor did they consume 60-ounce diet drinks and “fat free” snacks in hope of losing weight. Until the twentieth century, starvation reigned as the number-one killer of humankind. While it still is in many places around the world, technological innovation has brought rapid and dramatic improvements to our food production, supply, storage, transport and distribution. The COVID-19 pandemic has demonstrated just how complex and fragile this system is, and for the first time in recent memory, we are starting to question whether our food delivery can be sustained.
Yet even in the midst of global economic meltdown, we still have more food and calories available per capita than any other time in human history, From an evolutionary standpoint, it’s almost as though we just arrived here yesterday… these remarkable advances occurred in the span of one generation. Yet today, obesity - and its numerous co-morbid conditions - have supplanted starvation as the number one cause of preventable death in the US. In fact, the most impoverished persons in the US are also the most obese. Why? Highly processed carbohydrates are readily available and cheap. We’ll go deep on this later, but it should be no surprise to most of us that it’s now possible to eat in one sitting what our ancestors might have eaten in an entire week, all for the price of an hour’s-worth minimum-wage work. We truly are rolling in an abundance of cheap, low-quality calories.
That being said, the science also reveals that overeating and sedentary living cannot fully explain the cause or pathophysiology of the unprecedented prevalence of obesity. Something else is happening. Indeed, our genetics have not adapted to accommodate the caloric excess and abundance in our society. Translational research by Drs. Ken Blum and Mark Gold note that one of the reasons we are alive today is that our ancestors carried what has been colloquially dubbed, the “thrifty gene.” This genetic blessing enhances the efficiency of storing calories as fat, thus increasing one’s chance of survival during times of scarcity and famine. Having this genetic advantage was directly correlated with survival, so the thrifty gene was more readily passed down to the offspring. Conversely, those without this genetic trait often perished due to their inability to efficiently store calories as fat during times of scarcity and famine.
As a result of these genetic and evolutionary forces, the thrifty gene is widely prevalent today, however it is no longer a blessing in times of abundance, which has been the norm for nearly a century in the US. As a result, the thrifty gene has become a curse, as convenient, highly processed-carbohydrate food sources are everywhere. The best available evidence suggests that this this change happened faster than we could adapt as a species. The same thrifty gene is still sending signals to eat and store fat in preparation of famine. Thus, our genetic or environmental factors are combining in an unanticipated way to put us at risk of becoming overweight and obese.
Our natural state is hunger. Ghrelin, colloquially dubbed as our “hunger hormone” is in fact a complex neurohormone produced primarily in the gut with minuscule amounts released by the pancreas and brain. Ghrelin is the only known circulating hormone that stimulates appetite and promotes adiposity due to its “orexigenic” function - it makes us hungry.
Within the brain, the hypothalamus acts as a “thermostat” to mediate and modulate numerous physiological functions that are continually adapting to both internal and external stimulus in order to maintain homeostasis for optimal function. The hypothalamus contains the highest density of ghrelin receptors in the body that stimulates orexigenic function, e.g. feelings of hunger, initiating feeding, and finally fat storage through several mechanisms in the hypothalamus. Clinical studies have shown that when ghrelin is artificially given to human subjects, it produces hyperphagia (ravenous overeating), increasing food intake by about 30% per day.
If ghrelin causes hunger and ravenous eating, then how or why do we stop eating?
Leptin, from the greek word “Leptos” (meaning thin), is a hormone predominantly made by adipose (fat) cells and enterocytes in the small intestine. This hormone is released in a pulsatile manner to regulate energy balance by turning down the hunger signal, which in turn diminishes fat storage. When enough calories are consumed for survival, leptin binds to its receptors in the hypothalamus to inhibit the action of ghrelin. This action produces satiety, enabling us to sense fullness and recognize that we have eaten enough food.
The brain is under the influence of two hormones which control the sense of hunger: Ghrelin and Leptin. Ghrelin stimulates the hypothalamus to cause hunger and drive eating. Leptin is released from the fat tissue to block the function of ghrelin when enough calories (energy) have been consumed causing a state of satiety.
Glucose is our main source of energy and is present in the body as "circulating" glucose and "stored" glucose (in the form of glycogen. When we take in an excess of glucose, it becomes converted to triglycerides and stored in our fat cells, increasing our "adipose reserves." Blood leptin levels correlate with the amount of circulating and stored glucose, as well as adipose reserve. When leptin is released, it is designed to take control by modulating complex neural circuitry involving both orexigenic and anorexigenic signals to exert energy balance (homeostasis).
More recently, researchers discovered that outside of the hypothalamus, leptin also interacts with the mesolimbic dopamine system in the midbrain and lower brainstem. This is the central headquarters for our autonomic nervous system. Here, activation by leptin produces motivational salience, pleasure, desire, and reward for behaviors necessary for survival, such as feeding, hydration, copulation, and rest. These actions of leptin assist in regulating energy balance, which feels good.
Simply stated, ghrelin drives us to feed. Then, when enough calories are consumed to assure survival, leptin turns off the hunger signal in the hypothalamus by inhibiting the action of ghrelin. Thus, under normal conditions, these neurohormones are in balance and mediate hunger and satiety to achieve energy homeostasis.
In other words, when we've had enough to eat, leptin is released in the bloodstream and should kill our appetite. Should.
However, achieving that balance nowadays is extremely hard. Clearly, lifestyles in the late 20th and early 21st centuries may seem normal to us but in fact are aberrations in human anthropological history. Today in the US, we have an unprecedented abundance of food--more food than we can consume. As a result of our thrifty genes and abundance of food, most of us eat too much and too
often--not because we are calorie deficient or actually hungry, but because tasty, highly palatable food is everywhere. This negative feedback loop produced by the effect of ghrelin and leptin is similar to the mechanisms for mediating and modulating many different physiological functions, such as respiratory rate, body temperature and blood pressure. For this reason, the hypothalamus has been called the body’s thermostat.
"I know I have to lose 70 pounds. I have several medical conditions because of my weight, I take 8 prescription medications per day, and I am always hungry. I eat a salad with my coworkers at lunch so they won’t think I am a glutton, but I literally graze all day on snacks, some of which I hide in my desk. After work I pick up a semi-healthy meal to eat at home, but then I continue snacking all night. I have baked frozen pizzas at 1 am, more times than I can recall. I have tried at least 9 diets, joined weight watchers, and fail every time. I am so lonely and feel so ashamed of the way I look. My depression is overwhelming at times. I don’t know what to do... I am losing hope." -----Cassandra, 41, Sr. Account Mgr.
But what if you didn’t produce enough leptin, or were resistant to the function of your own leptin? Without effective leptin signaling, ghrelin would continue sounding the hunger alarm. Research over the past two decades has shown that low leptin levels or resistance to the effects of leptin result in overeating, obesity, and their metabolic complications. Many of our patients report that they are always hungry and no one believes them. We do. Our research and clinical experience has shown us that for some... their stomachs may be full, but their brain tells them that they are starving.
A deeper dive into the neurobiology of hunger and satiety show that for a subset of overweight and obese persons, eating highly palatable, processed carbohydrates has taken control through the same neuroadaptational mechanisms that occur in substance use disorder (SUD). This type of overeating is hedonic, and it is part of the pathology of hijacked perception. All mood altering substances and behaviors usurp the reward system by producing a neurobiological reward, such as the sensation of pleasure, euphoria, calm, sedation, or escaping the emotions of physical distress.
"Hedonic overeating" - he·don·ic /hēˈdänik/ adjective: relating to or considered in terms of pleasant sensations.
Using the latest and most advanced imaging technology, a Positron Emissions Tomography (PET) scan, researchers have identified the brain circuitry and neurobiological deficits that is hijacked among those with known risk factors. As a result the vulnerability for addictive disease, including drug or alcohol addiction, gambling, hypersexuality, and hedonic overeating is higher than for the person without these risk factors. (see Figure 2).
Figure 2 - Composite brain scan images taken via Positron Emission Tomography (PET) demonstrate that “obese subjects have significantly fewer dopamine receptors (shown as red) in the outined area than control subjects. These receptors transmit pleasurable feelings from basic activities such as eating, socializing, and sex. Low levels of these receptors also have been found in people addicted to drugs of abuse. The reduced reward experienced by people with this deficiency is a well established risk factor for addictive disease as both drugs and for some, overeating spikes their depleted dopamine level well past what any natural reward could produce (Volkow, Wang, et al., 2006)."
It turns out that there’s a lot of overlap between those who are addicted to drugs and those and become obese. The correlates are:
Motivation and drive
Learning and conditioning, and
Loss of inhibitory control and emotional dysregulation via executive function.
Interoception - Our System of Internal Perception
The Interoception Network has been found to play a role in hedonic overeating and substance abuse. This Network of neurons (Figure 3) includes parts of the brain known to be involved in thinking thoughts and taking action, including the insula, striatum, cingulate, and prefrontal cortex. "Interoception" refers to a function of the central nervous system by which individuals become aware of their visceral sensations, feelings and internal body states. The Interoception Network functions to integrate both internal and external sensations or signals with our cognitive, emotional, and motivational networks to recognize and respond to physiological sensations. When it becomes impaired, individuals may fail to respond appropriately to physiological cues and sensations that are protective.
Figure 3 - the Interoception network and how it works.
The consequence of the disruption of these circuits is the high value associated with the reinforcing agent (drugs for the drug abuser and highly processed carbs for the hedonic overeating, obese individual), all at the expense of one’s true values. This is, in part, the consequence of abundance, conditioned learning and neuroadaptation that redefines reward, pleasure and happiness and manifest as hypothalamic dysregulation, secondary to repeated stimulation by large quantities of highly palatable, processed carbohydrates in vulnerable individuals.
The epidemic of mass-scale overeating is not due to scarcity or that people need these calories, but rather neuroadaptations in the reward circuitry and hypothalamic dysregulation, as mediation of hunger and satiety signals are usurped to the degree that the brain's “hunger switch” remains stuck in the “on” position.
Yes, we made this word up. But it works, when you consider the notion that someone can lose the ability to identify and process visceral feeling, Just like someone with visual agnosia will have a lack of perception of what they are seeing, those with interoagnosia will have a lack of perception of how why they are eating and how much they are eating. Neither case represents a moral flaw or character deficit but a neurobiological condition that manifests as lack of awareness of our internal reality and actual survival needs.
Interoception is the ability to sense what is going on' inside one’s body, accurately interpreting the cues and signals. Hunger (ghrelin) cues the drive to eat eating stops when leptin inhibits the action of ghrelin in the hypothalamus. Overeating and obesity are evidence that huger and satiety signals are usurped which results in consuming highly palatable carbohydrate that acutely elevates their brain’s dopamine which provides an acutely pleasurable, but unnatural reward that leads to obesity and all that goes with it.
After becoming obese I'd promise myself I am going to lose this weight. But after a few days of whatever new diet or exercise program I began, the world seemed dull and boring--like watching a 12 inch black and white TV. I’d finally convince myself that everyone needs a “cheat day” especially when work was stressful. So I’d order a pizza and after 2 slices, it was like the color came on, and my life was in high definition for a few hours, then the guilt and self shaming would begin, and I’d be right back where I started. -- Fat, alone and miserable.
--Jasmine--24, graduate student, Economics
Likewise, people with interoagnosia suffer from a genetic or acquired inability to attain energy balance and therefore fail to attain satiety due to a leptin insufficiency or resistance at the molecular level. Accordingly, their hunger drive and pattern of overeating is pathologically derived. Others, get there by way of Reward Deficiency Syndrome, a heritable and sometimes acquired deficit in the bioavailability of the powerful excitatory neurotransmitter, Dopamine. Their neurohormonal adaptations have corrupted their energy balance and ruined their capacity to attain satiety. They can't recognize or respond to the risks of overeating, as they won't feel normal without overeating. Interoagnosia blinds one to the sensations of self-harming behaviors without being aware of the longer term consequences or ramifications of their preoccupation with eating.
What Does This Mean For Me?
If your perceptions have been hijacked, then it's time to make a change in your life, before nature forces the change on you. The good news is that it's actually easier than you might think. You see, one of the most important discoveries of the last century is that the brain has a characteristic of "neuroplasticity," meaning it is capable of rewiring itself. Just as your brain can adapt to abundant sugar calories that drive addictive behaviors, it can also readapt to a healthier status. It all starts with making a decision, and you are the only one who has the power to make this happen.
Summing things up...
Stay tuned for Part 2, where we discuss Reward Deficiency Syndrome and the Neuroscience of Food Addiction.
Personalized Behavior Management
In previous posts, we've discussed how Reward Deficiency Syndrome, Depression, and Addiction share genetic and environmental factors that interact with one another to degrade performance and interfere with healthy relationships. Fortunately, an emerging model of treatment based on Forgiveness provides real hope for the rescue and recovery of people suffering from these factors. Our approach is to provide access to Personalized Behavior Management using tools that lower the barriers to care. Our dream is to help bring about personal transformation on a large scale so that mental health and quality of life flourish. To get started with your own Personalized Behavior Management therapy, schedule a meeting with us today!
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