Image copyright 2016 New York Times. Included under the provisions of fair use under U.S. copyright law.
In 2013 the American Medical Association declared obesity a complex, chronic disease requiring medical attention. The intention behind this move was to require physicians to start treating obesity and require insurances to pay for treatment and prevention. Hopefully, giving health care providers and insurances a nudge to treat obesity would reduce the prevalence of costly diseases such as type 2 diabetes and cardiovascular disease.
The backlash was instantaneous.
For starters the AMA House of Delegates overrode a recommendation made by the an AMA expert panel. In their statement the experts cautioned that a better diagnostic criterium for obesity would need to be developed given the limitations of the BMI. Despite the BMI shortcomings the expert panel still preferred to classify obesity a condition or disorder, but was overruled by the house of delegates.
While part of the medical community applauded the decision others cautioned that this move would have rather detrimental affects. Treatment of a disease tends to focus on pricey drugs, medical technology, surgical procedures and expensive clinic visits instead of addressing the root problems of the obesity pandemic. Given the millions of affected Americans some were concerned that the cost of treatment would be staggering.
Others pointed out that a disease designation would move the blame to the individual and would lead to increased weight discrimination. There was also concern that people would be released from personal responsibility and somebody else—the government, medical establishment—would be in charge.
Years later, the uproar has subsided, but different camps are still arguing about how to approach obesity. Physicians and other medical personal still haven’t learned how to address weight in the examination room and weight discrimination is rampant in the medical system. On the other hand some health care provider ignore the physiological facts (f.e. “Healthy at Every Size” https://haescommunity.com/) and focus mostly on the psychological arguments. Desease designaton or not, health care providers need to understand the connection between obesity and chronic diseases and need to be trained to address weight in a health care setting.
During this first module you will learn about the connection between obesity, systemic chronic inflammation (SCI) and chronic disease. Once you have a solid understanding of this interaction we will explore how lifestyle decisions at every stage of life can increase or decrease the risk for obesity and chronic diseases, and ultimately determine the long-term quality of life.
At a very basic level obesity is an increase of adipose tissue. Before you dive into the next chapters you should review what you already know about adipose tissue.
The following review slide summarizes facts about adipose tissue, BMI, the difference between the two, and how both are evaluated. If you have trouble understanding the slide you might need to go back to your notes or grab a textbook and review:
What happens when you have too much body fat? If you believe the media then people can be healthy at any weight. This statement is too simplistic though. While some overweight and obese people—10 to 30 %—do not have any obvious health problems, we know that obesity and to a lesser degree overweight increases the risk for non-communicable diseases such as cardiovascular disease (CVD), hypertension, type 2 diabetes (T2D), some cancers, non-alcoholic fatty liver disease, osteoarthritis, rheumatoid arthritis and reproductive issues. There is even newer research showing that dementia prevalence is higher in obese individuals.
When we talk about obesity it is important to keep in mind that not everybody who is obese will develop those diseases. But, we need to separate personal risk and public health impact. Even if only a small fraction of the 70 % of Americans who are overweight and obese develop one or more non-communicable diseases it becomes a public health issue. Obesity is a major contributor to disability, medical costs, lost years of life and generates a huge societal cost.
The scientific community has researched factors contributing to obesity for a long time. This evidence started out with a solely personal or genetic explanation (genetic predisposition, overeating, insufficient physical activity).
During the last decades this research expanded increasingly to environmental factors. Based on this extensive research we know that obesity is not just an issue of lacking will power. It became increasingly clear that obesity is a very complex multi-factorial process.
Genetic predisposition determines where body fat is stored and to a smaller degree how much is stored. Some people have a more efficient metabolism and are respond to temporary overeating by putting on weight (“thrifty metabolism”). During famines, which were common not too long ago, this genetic feature was a plus when it came to survival. Today, in an environment of constant abundance, a thrifty metabolism makes those people more prone for weight gain and ultimately chronic diseases.
Others have a genetic predisposition and store fat predominantly around the midsection. This is called central obesity. If the central adipose tissue is located around the organs inside the abdominal cavity it is called visceral obesity. Central obesity is more common in men and that is why it is named android obesity. Gynoid obesity is more common in women with increased fat deposits around hips and thighs.
With age fat stores tend to increase and storage tends to shift toward central and visceral obesity in both genetic types. A genetic predisposition and advancing age do not necessarily mean that a person will become obese. It just will require much more work to maintain a healthy weight.
Eating a diet with a high energy density—high in added sugar, high in fat, low in fiber-rich plant food—makes it more likely that a person becomes overweight or obese. Research shows that people eating a plant-heavy diet, limiting fatty and sugary meals and reducing the consumption of ultra-processed foods maintain a healthy weight throughout life much easier.
Avoiding a sedentary lifestyle, increasing physical activity and regular exercise support the nutrition side. While exercise, unless it is very extensive and intense, is often not sufficient to maintain a healthy weight, exercise and physical activity contribute to improved health and reduce the risk of non-communicable diseases at any weight.
Today, we also understand that obesity is not solely due to personal decisions or a lack of willpower as many still believe. The food environment impacts weight as well. In the US living a healthy lifestyle is an uphill battle at best and for underserved groups often not accessible. Availability of healthy foods at a reasonable prize, developing food preparation skills, and city planning that promotes physical activity would make it easier to choose healthy options.
Learned health behaviors such as how we choose food and how we eat our meals determine the trajectory of our weight. Psychological factors such as body perception and the ability to monitor food intake can help maintain weight or start a weight gain spiral.
Newer research also shows that other lifestyle choices promote slow weight gain. Lack of sleep and chronic stress might not be main factors for weight gain but contribute.
Based on this extensive knowledge health professionals developed health policies, recommendations, and intervention programs. Of course scientists researched the success of these programs and the results are rather disappointing. Health policies and programs are frustratingly ineffective. Even if people lost a good amount of weight the weight came back soon with a vengeance. Only 5 % of people losing weight will maintain the new lower weight long-term. Despite what the media says, that holds true for the popular keto and low-carb diets as well.
What is going on? Did those scientists miss anything?
This is the point where this course will expand on your existing knowledge. The following textbox highlights what you will learn during this chapter.
You Will Learn:
1. Eat less, exercise more? It is not that simple.
- The homeostatic pathway regulates energy intake and expenditure.
- The hedonistic pathway stimulates eating via a reward system.
- In time of food abundance the hedonistic pathway overrides the homeostatic pathway.
2. Adipose tissue is not just an energy store, but an endocrine organ.
- Leptin signals energy status to other organs.
- Adiponectin is involved in regulation of glucose, fat metabolism and immune response.
- Cytokines signal inflammation status within a tissue and between tissues and organs.
3. Obesity increases systemic chronic inflammation (SCI).
4. Not all obese and overweight individuals are metabolically unhealthy.
Eat Less, Exercise More? It is Not That Simple
Overweight and obesity are contributed to an imbalance between energy intake and energy expenditure. This is a scientific fact. The paradigm Eat less, exercise more was the standard recommendation for maintaining a healthy body weight for a long time.
The scientific fact of an energy imbalance is often mixed up though with the much more complicated question why this energy imbalance happens in so many people today. While some are still pushing the old recommendation, we know today that the regulation of energy balance and with that the maintenance of body weight is much more complex than this simple recommendation.
Before we look at the consequences of obesity in more detail you should understand the principles of food intake regulation.
First there are the two major physiological pathways regulating food intake.
One is the homeostatic pathway that regulates the homeostasis between energy intake and expenditure. This pathway increases the motivation to eat when energy stores are depleted or increases satiety when sufficient amounts of food were eaten.
The command center of the energy homeostatic pathway is the brain and there are two major inputs.
During digestion the stomach is distended and this signals the amount of food eaten to the brain. While food is digested hormones are secreted to regulate the digestion but also prepare the metabolism for the incoming nutrients. The hormones secreted during digestion also feed back to the brain and signal to suppress appetite depending on macro-nutrient composition and food amount. This is the reason why we usually do not have a drive to eat right after a meal.
The second input is the signaling from existing energy stores. Leptin is one of the hormones involved here. A decrease of leptin secretion with shrinking adipose tissue increases the drive to eat. Increasing leptin secretion with growing adipose tissue tends to reduce appetite.
Interestingly, the drive to eat during an energy shortage is much more potent than the down regulation when energy becomes abundant again. As a result gaining weight is much easier than losing weight.
Eating does not just provide energy and nutrients but is also a pleasurable experience. This is where the second pathway, the reward-based regulation or hedonic pathway, comes in. The inputs for the hedonic pathway vary. They include visual cues, smell, taste, chemical and hormonal triggers. These cues mostly stimulate the pleasure center of our brain.
During times of abundant food supply the hedonic pathway will override the homeostatic pathway by increasing the desire to eat palatable foods. Today’s food environment supports this physiological overeating by providing ubiquitous and abundant amounts of very tasty food.
The physiological bias toward overeating is further aggravated by psychological factors. Some individuals have excessively restricted eating behaviors while others eat uninhibited. External cues such as the constant presence of food or food advertising trigger more and frequent eating. Emotions ranging from being bored to happy to sad to stressed can also influence how much we eat. How much those psychological factors impact eating decisions varies widely between individuals.
Nutritional and non-nutritional factors such as food composition, meal size, plate or serving sizes alter our eating behavior. For exampl people eat more when served a larger portion. This aggravates the overriding of the homeostatic energy regulation even more.
In conclusion: Hedonistic regulation and psychological eating tend to override the homeostatic energy regulation in today’s obesogenic food environment. As a consequence overeating is common. Once weight is gained the features of the homeostatic pathway makes it easier to gain weight and harder to lose it.
This said, we all react differently to the food environment. Eating behavior develops during childhood and early adulthood based on our food and eating experience which is determined by our social environment and cultural experience.
In part this explains why the old eat less, exercise more recommendation usually fails.
Adipose Tissue Is Not Just an Energy Store But an Endocrine Organ
So far, we established that eat less, exercise more is too simplistic to explain why people fail to maintain a healthy weight. People gain weight over a lifetime as a combination of personal, environmental and learned behaviors. The question is now why health interventions and nutrition policy are not able to turn the obesity epidemic around by addressing these factors.
You will understand why when you understand the function of the adipose tissue and the metabolic changes that happen progressively during weight gain.
Before the early 1990s we thought that white adipose tissue, or WAT for short, is composed from adipocytes and blood vessels. We thought that chylomicrons deposit part of the fat after a meal directly into the adipose tissue. In addition, very-low density lipoproteins (VLDL) transport triglycerides produced by the liver from surplus carbohydrates, amino acids or alcohol to the WAT.
There, lipoprotein lipase in the blood vessel wall is activated and hydrolyzes the triglycerides. The fatty acids can now pass into the adipocyte where they are rapidly re-esterified and stored. When the energy is needed the triglycerides in the adipose tissue undergo lipolysis and fatty acids are released directly into the circulation and are taken up by cells in need for energy.
While this is still correct today, our knowledge about adipose tissue expanded immensely since then.
The figure on the left shows the cells of the adipose tissue. In addition to the fat storing adipocytes, adipose tissue also contains a plethora of secretory cells. These secretory cells synthesize chemicals that trigger or damp the hunger and satiety mechanism. Other functions are regulating blood pressure, triggering an immune system response, modifying glucose and lipid metabolism, regulating reproduction, maintaining bone homeostasis, regulation vascular growth and many more (infographic above, right).
Many of those messenger chemicals are also produced by other endocrine tissues and they collaborate to regulate the bodily functions mentioned above.
The adipose tissue also produces and secretes chemicals that are only secreted by the adipose tissue. These are called the adipokines. Adipokines are small peptides that are secreted into the vascular system and message the status of the adipose tissue to other tissues and organs. Targets include the brain, liver, pancreas, immune system, vasculature, muscle, and many other tissues. It is estimated that over 600 adipokines exist but they are by far not all researched. The best researched adipokines are leptin, adiponectin and to a lesser degree resistin.
Since this line of research is fairly new, we need to keep in mind that research is ongoing. While we lack understanding how those secreted chemicals work together, we do understand that expanding adipose tissue changes the secretion of those messenger molecules profoundly. As a consequence increasing fat mass changes how the metabolism works.
There is no way to address all those messenger molecules in this chapter. Instead we focus on several molecules that are important to understand the connection between obesity and chronic diseases. Let’s have a look at those specific messenger molecules in the top portion of the next infographic. You will study the basics for the adipokines leptin, adiponectin and resistin as well as the hormones estrogen and cortisol, and the chemokine cytokine.
The adipokine leptin is a small protein that signals the energy availability of the adipose tissue to other organs. Primarily, leptin signals to the brain regulating satiety, but the same signals are also used to fine tune fertility, inflammatory state and many more.
As adipose tissue grows—let’s say during the holiday season in November and December—it releases more leptin into the blood stream. Receptors in the brain measure the increasing amount of leptin and signal fullness. When we work off those pesky pounds later in January leptin blood levels fall with shrinking adipose tissues and that makes us hungry.
If we don’t lose the weight and instead steadily increase adipose tissue, leptin blood levels keep increasing as well. Once leptin blood levels are persistently high you would think that the body keeps signaling fullness, but now a counter regulation kicks in. The body becomes leptin resistant. This means since there is so much leptin in the blood the body produces less leptin receptors in the target organs. Leptin becomes now ineffective to signal energy status and satiety. In leptin resistance falling leptin blood levels during weight loss are registered by the confused brain as a starvation period and severe hunger will set in.
Adiponectin: While leptin secretion increases with growing adipose tissue, adiponectin secretion declines with growing adipose tissue. Adiponectin is less researched than leptin. So far we know that adiponectin is involved in the regulation of blood glucose levels, fatty acid breakdown and regulation of the immune response.
In lean people adiponectin circulates in high amounts and seems to have a protective effect against insulin resistance. The primary mechanisms by which adiponectin enhances insulin sensitivity appears to be through increased fatty acid oxidation and inhibition of hepatic glucose production. The anti-inflammatory properties of adiponectin reduce atherosclerotic processes in the blood vessels.
Adipocytes are also able to produce cytokines and the amount produced is proportional to the amount of adipocytes. The more adipose tissue the more cytokines are secreted. Cytokines—note that cytokines do not belong to the group of adipokines—are small messenger proteins and part of the cellular immune response. Cytokines are secreted by many cell types to signal an inflammatory state. They can either be secreted into the interstitial space between cells, signaling inflammation to other cells in the same tissue, or directly into the blood circulation transmitting the inflammation signal between organs.
Cytokines attach to corresponding receptors of target cells and modulate the metabolism of the target cell. That way cytokines coordinate the immune response between cells in the same tissue, but also the immune response between cells of different tissues.THis changed regulation has impact aside of the immune response. In insulin sensitive cells such as muscles increased amounts of cytokines decrease insulin sensitivity.
I would like to touch on two more secretory adipose tissue functions you will need to keep in mind for the fertility, type 2 diabetes and hypertension chapter.
Cortisol the main stress hormone in the body is involved in the regulation of glucose metabolism. Higher blood cortisol levels result in higher blood glucose levels. In a stressful situation more available glucose means more readily available energy. Originally, this mechanism helped the muscles react fast during the fight-or-flight response. Adipose tissue does not produce cortisol directly, but has an enzyme that converts the pre-cursor cortisone into cortisol. Therefore more adipose tissue results in higher cortisol blood levels which in turn maintains higher blood glucose concentration.
Adipose tissue contains an enzyme called aromatase that converts androgens, the male sex hormones—even women have low amounts—into estrogen the main female sex hormone. In consequence estrogen blood concentrations will rise with increasing adipose tissue in men and women. Keep this in the back of your mind until we talk about fertility and pregnancy.
RAS (renin–angiotensin system): We will get back to this later when we talk about obesity induced hypertension. Scientists think that adipocytes are able to secrete angiotensinogen the starting point of the blood pressure regulation. Adipose tissue also has high levels of the enzyme ACE. One of the function of ACE is to convert angiotensin I into angiotensin II. This mechanism can lead to increased blood pressure as adipose tissue growth.
Obesity Increases Systemic Chronic Inflammation (SCI)
Everybody talks about low-grade inflammation. Blogs and webpages warn of inflammation causing foods, recommend inflammation reducing diets, and peddle inflammation-reducing supplements. What is it?
Quick Biology Review:
The innate immune system is the first line of defense against micro-organisms, foreign molecules, injury and cell death. The innate immune system is rapid, non-specific and non-anticipatory. The goal is to remove foreign or dead material—microbes or damage to cells and tissues—and communicate to the adaptive immune system. The innate immune system uses phagocytic and inflammatory cells as well as messenger proteins to coordinate both immune systems.
The adaptive immune system is specific and learns to anticipate and recognize foreign material. The response involves the binding of antigens and the secretion of immunoglobulins.
One type of cells that will keep coming up are the Macrophages. Macrophages are part of the innate/unspecific immune system and serve as a first defense. They derive from monocytes and have three broad functions:
• Identify foreign molecules or microbes and remove those via phagocytosis (envelop and destroy).
• Remove dead and dying cells in injured tissue via phagocytosis.
• Secrete cytokines and communicate that way with the adaptive immune system and other tissues.
Balance is important: We tend to think about an immune response as a swift and hard intervention once the immune system is triggered but the opposite is true. Immune responses need to be measured and balanced because the processes will not just remove the virus or bacterium but damage tissue in the process. Think about the dreaded cytokine storm in COVID-19 patients or auto-immune diseases. The goal is to balance removal with as little damage to body tissues as possible.
When a white adipocyte becomes very large—above capacity—they will start leaking free fatty acids (FFAs) into the surrounding adipose tissue. Since FFAs can freely pass through cell walls they will reach macrophages embedded in the adipose tissue. At the same time the super large adipocytes can become hypoxic and are more likely to undergo cell death (apoptosis).
Leaking fatty acids and dead cells shouldn’t be in a well functioning adipose tissue and this prompts an innate immune reaction: The macrophages, embedded in the adipose tissue, secrete cytokines into the interstitial space between adipocytes. The cytokines start diffusing in the adipose tissue and bind to receptors on the adipocyte surface. This signals an inflammatory state to other adipocytes.
This inflammatory signal changes the adipocyte metabolism and turns the adipocyte into what is called an inflammatory phenotype. This means that the adipocyte starts now to produce cytokines and other messenger molecules signaling the inflammatory status.
The cytokines in concert with other secreted messenger proteins increase inflammation in the adipose tissue. Increasing inflammatory signals will attract other immune cells such as monocytes from the blood stream. The monocytes can differentiate into macrophages and the newcomer macrophages start secreting cytokines as well. You get the point. The adipose tissue is now in a vicious inflammatory cycle.
There is another aggravating factor. In lean individuals the adipose tissue secretes smaller amounts of leptin and larger amounts of adiponectin. One function of adiponectin is to suppress macrophage activity and keep the innate immune system in balance. Falling adiponectin concentrations takes the break from the immune response enhancing the excessive inflammatory response not only in the adipose tissue but in other tissues as well. SCI (systemic chronic inflammation) develops.
Expanding adipose tissue has the potential to become inflamed but the inflammation does not remain contained in the adipose tissue. Cytokines signal not only to cells in the same tissue to coordinate the immune response, but cytokines are also secreted into the blood stream and signal the inflammatory status of the adipose tissue to other tissues and organs. This chronically elevated secretion of cytokines is what we call systemic chronic inflammation or SCI for short.
The inflammation messengers cytokines coordinate the metabolism of many tissues and organs: Inflammation is not just a reaction of the immune system. Signaling molecules such as cytokines alter the entire metabolism profoundly for the short time the body is fighting the infection. Inflammation, as you all know from your last bout with flu or even soreness after an intense exercise session, triggers sickness behavior. Depending how severe the inflammation is, this will include sadness, anhedonia, fatigue, reduced libido, reduced food intake, altered sleep and social withdrawal. At a metabolic level inflammation increases insulin resistance and causes dyslipidemia. When you look at these metabolic and behavioral effects of inflammation it becomes clear that the purpose of those adjustments is to save energy and direct resources to the immune system. These reactions from other tissues ensure survival if life is threatened by a physical injury or a microbial threat. In SCI the metabolic adjustments become permanent and have a negative impact on health.
The circulating cytokines dock to receptors on the cell surface of other tissues. This changes the cell metabolism of those tissues as well. For example cytokines can dock to blood vessel epithelium triggering an inflammatory response or can dock to cells changing insulin sensitivity. Systemic inflammation contributes along with other risk factors to T2D, CVD, kidney disease and other chronic diseases. Recently evidence emerged that systemic inflammation might contribute to cognitive decline and dementia as well.
Not every obese person develops chronic diseases, but evidence is strong that systemic chronic inflammation triggered by an inflamed adipose tissue in obesity is the reason why non-communicable chronic diseases are much more common in obese individuals than in individuals in the normal and overweight range.
Emerging Science: EVs Enable Cells to Talk to Each Other
So far you learned two routes of communication between the adipose tissue and other cells and tissues: The adipose tissue secretes hormones and cytokines depending on the metabolic state of the adipose tissue. During the last years scientists discovered another important communication system between cells, tissues and organs: Extracellular vesicles or EVs for short.
What are EVs? All cells release extracellular vesicles as part of their normal metabolism. EVs are tiny vesicles, a piece of membrane surrounding cargo (see image to the right) that is transported from cell to cell. The cell membrane can either come from the endosome which are then called exosomes (more about those specific EVs later.) The EV can also be pinched off from the cell membrane. The inside of the vesicle contains a cargo of regulatory proteins, lipids, DNA and RNA. EVs are secreted into the extracellular space and can either travel to other cells or specific target cells. Those target cells can be within the same tissue or the EVs are transported by the blood circulation to other tissues. Initially, scientists thought that EVs remove surplus cell material, but over the last decade it became increasingly clear that cells use EVs to communicate with each other. Depending on the metabolic situation cargo varies or the cell can regulate how many EVs and what type are secreted.
On a sidenote, proteins embedded in the EV membrane can direct the EV to a specific tissue or cell. A brandnew area of research investigates how to use exosome shells to transport medication to specific cells in the body. For example, this would enable us to transport a chemo drug that wreaks havoc on all cells in the body only to the tumor leaving other cells unharmed.
What are the functions of EV? As you can imaging EVs have many functions. Studying nutrition sciences, the focus research tends to be on exosomes because they are involved in the coordination of the metabolism, interaction between muscle metabolism and health, coordination between gut microbiome and metabolism, inflammatory processes, development of insulin resistance, CVD, cognition, pregnancy, lactation to name a few.
You are what you eat? Exosomes are not just produced by human cells: As research evolved scientists made a couple of surprising findings that are important for nutritionists and dietitians. The first one is that exosome shells can withstand digestion. Since all cells produce exosomes, unprocessed food will contain exosomes as well. These exosomes can pass through our digestive system and act on our gut microbiome, but can also be absorbed into the blood circulation. In mice exosomes were detected in the liver, spleen, and brain. In humans miRNA found only in milk exosomes, can be detected in the blood circulation when study subjects drink milk. This research is brand-new, and the main question is how food exosomes impact cell metabolism or the gut microbiome. Secondly, our gut microbiome also produces exosomes that end up in our blood circulation and have the potential to alter cell metabolism.
Not All Obese and Overweight Individuals Are Metabolically Unhealthy
Why are many obese individuals, but also some overweight or lean individuals, metabolically unhealthy? Why do some obese teenagers develop T2D and CVD already in their teens while others don’t develop those diseases until old age or not at all despite being obese all their life?
Lifestyle and our environment play a large role. The grade of obesity, level of sedentary behavior, a processed food diet, sleep deficit, isolation and chronic stress determine the amount of adipose tissue and to a lesser degree where it is located. Those factors also contribute to SCI.
Genetics and age play a role by determining where the adipose tissue is located, how the adipose tissue grows and how adipocyte function.
Some people have a genotype that increases adipose tissue by generating more smaller adipocytes. This is called hyperplasia and less connected to systemic chronic inflammation. Other people’s metabolism fills up existing adipocytes to capacity producing very large adipocytes. This is called hypertrophy. Overly large adipocytes are connected to systemic chronic inflammation.
What is brown adipose tissue? For the longest time we thought that only infants have substantial amounts of brown adipose tissue. Recently, evidence is mounting that white adipose tissue can beige or brown. Mechanisms are not fully understood, but we think that exercise is one factor that can trigger browning. What is so special about brown adipose tissue? While white adipocytes have only few mitochondria and store fat, brown adipocytes have many mitochondria and burn fat to produce heat. White adipocytes, especially from visceral adipose tissue, have the tendency to become pro-inflammatory as they grow, brown adipocytes are anti-inflammatory.
The location of the adipose tissue is important. Visceral obesity—excessive adipose tissue located within the body cavity—fuels systemic chronic inflammation more than subcutaneous adipose tissue. Even some lean individuals have excessive amounts of visceral fat and therefore develop SCI.
As people reach middle age adipose tissue location start to change. Hormonal changes in middle age promote central and visceral obesity. Details are discussed in the aging chapter.
In summary the current evidence points toward overly large adipocytes and visceral obesity as the main predictors for SCI. But, does this mean that people with this type of obesity automatically develop CVD or T2D early in life and die early?
Lifestyle plays a major role as well. Eating a diet rich in fruits and vegetables and having an active life style promote anti-inflammatory mechanisms and curb SCI. As a consequence metabolic disease progresses more slowly even if a genetic predisposition exists. Regular exercise lowers inflammatory processes.
This explains partially why some overweight and obese people stay metabolically healthy for a long time while others develop T2D already in their teens. Keep in mind that the transition between those metabolic types is fluent.
- In lean people—without visceral adipose tissue accumulation—the adipose tissue functions as it should signaling satiety, helping to regulate glucose and lipid metabolism, and curbing excessive inflammation.
- An estimated 10 – 30% of obese people are metabolically healthy. Just like normal weight individuals this group of obese people doesn’t show any overt signs of metabolic disease. They tend to have very moderate SCI and only a mild metabolic dysfunction. The major question science tries to answer is if those healthy obese people also develop an unhealthy metabolic patterns with age. The problem is that we are lacking at the moment a solid indicator we could add to a lipid panel or a fasting glucose test at check-ups that can estimate the degree of SCI.
- People with a high degree of adiposity or a genetic profile that promotes visceral adiposity tend to have systemic chronic inflammation and manifested metabolic dysfunction. The normal regulation of metabolic function is pretty much hijacked by the hormones and chemicals secreted by the adipose tissue. Development of chronic diseases is apparent.
- Lean people with a high degree of visceral fat due to a genetic predisposition will have increased SCI and a matabolism that is not efficietly regulated. They have an increased risk for chronic diseases.
In conclusion, growing adipose tissue comes with profound metabolic changes. Hunger and satiety regulation becomes progressively inefficient, hormonal changes affect the metabolism, and systemi chronic inflammation alters the immune response and affects other tissues. Our understanding of these complex processes is still limited to broad ideas. Today, research works on understanding the mechanisms that connect growing adipose tissue to chronic diseases, browning of adipose tissue, and most importantly the reversal of those metabolic changes.
Interested? Want to Know More?
Obesity is a major source of systemic chronic inflammation but other factors contribute as well. Here is a Nature article reviewing what we know about the intersection of systemic chronic inflammation and the development of chronic diseases:
If you are as fascinated by exosomes as I am, here is a great review article going into more detail:
American Medical Association
Splits triglycerides into glycerol and fatty acids
Attaching three fatty acids to one molecule of glycerol
The inability to feel pleasure
Increased lipid and cholesterol blood concentrations
Endosomes are intracellular sorting organelles. They sort molecules and regulate traffic of molecules in the cells. This can include directing molecules to the correct cellular compartment, marking molecules for recycling or packaging cargo into exosomes.
Space outside the plasma membrane of a cell. The extracellular space includes the interstitial space (between cells) and the intravascular space (blood vessel system, lymphatic system.)
EV secreted by the endosome