The secret life of… fat cells
Adipocytes commonly known as fat cells, play a pivotal role that goes beyond storing excess energy and maintaining body warmth. Far from passive, these cells discreetly govern energy balance, shape immune responses, mitigate inflammation, and synthesise hormones. Here we will delve into the nuanced intricacies of fat cells and their profound influence in keeping us alive!
Fat Cell Basics
What is the medical term for fat cells?
Adipocytes. The word is derived from the Latin "adipo-" meaning fat and "-cyte" indicating a cell.
Any relationship between fat cells and adipose tissue?
Adipose tissue contains fat cells. Fat cells store and release energy in the form of lipids.
So, what’s inside fat cells?
Each fat cell contains a large single lipid or fat droplet housing chiefly triglycerides, also cholesterol esters, functioning as an energy reserve.
How many fat cells are in a human adult?
A human adult can have 30-40 billion fat cells but can vary significantly between individuals. A single lipid has a caloric density of approximately 9 kcal per gram.
What is a core function of fat cell?
Fat cells are both metabolic and endocrinal involved in the regulation of whole-body energy homeostasis.
What does metabolic mean?
Fat cells are actively involved in regulating how our body stores and breaks down energy from the food we eat.
What does endocrinal mean?
Fat cells produce hormones called adipocytokines that profoundly affect themselves and other hormones/cells in the body.
What is whole-body energy homeostasis?
Fat cells play an integral role in regulating our energy supply and demand.
What else can fat cells do?
Fat cells have a reservoir of stem cells to generate new fat cells and other cell types, including fat’s own immune cells.
So fat cells work with the immune system?
Yes, fat cells own immune cells are involved in aspects of regulating our immune system, including managing inflammation.
How do fat cells change and adapt?
Fat cells exhibit ‘plasticity’ properties, able to grow (hypertrophy), multiply (hyperplasia) and shrink (lipolysis).
Are there different types of fat cells?
Yes, white fat cells exhibit ‘phenotypic plasticity’, meaning they can transition between different functional states in response to environmental or physiological conditions.
Where are fat cells stored?
As subcutaneous fat under the skin and visceral fat in and around organs.
Are fat cells stored in other locations?
Yes, as essential fat in bone marrow, between muscles, breast tissue, and the liver and brain.
Is fat mass a simple equation of calories in/out?
No! Genes, hormones, pregnancy, puberty, menopause, gut microbiome, illness, fat cells themselves, and the environment all influence fat mass.
What do you mean by environment?
It includes where we live, what, when and how often we eat, pollution, substance use, sleep exercise and stress levels, light exposure, circadian rhythms, and temperature extremes.
Starting as we mean to go on
Adipocytes or fat cells, play a pivotal role that extends far beyond storing excess energy. Yet they frequently endure undue scrutiny, often associated with a stigma surrounding obesity—a complex condition that has been oversimplified in the popular press as too many calories in vs. out. Thanks to ongoing research, our comprehension of fat cells, and their interactions with various cell types and systems in the brain and body has reached an unprecedented level of knowledge that we can begin to bust some persistent myths.
We know that fat cells’ influence our mental and physical well-being, impacting us in both positive and challenging ways, depending on different factors. A blend of biopsychosocial factors, including genetics, physiology, emotions, cognition, and the environment can influence fat cells structure and function.
"The Secret Life of Fat Cells" reveals fat cells unassuming contribution to our immune (defence), endocrine (hormones), and metabolic (energy) systems. Highlighting their multifaceted functions, discreetly playing a pivotal role in regulating whole-body energy balance, modulating immune responses, attenuating inflammation, and synthesising hormones, helping sustain a delicate equilibrium keeping us alive!
Fat Cell ‘Plasticity’
Adipocytes exhibit ‘phenotypic plasticity’, meaning they can transition between different functional states in response to changing environmental or physiological conditions, changing in function, structure and colour. Altering their size (hypertrophy and atrophy), shape (modelling), and volume (hyperplasia). Additionally, new fat cells forming is known as adipogenesis. In some cases, fat cells can adopt characteristics of other cell types in response to intrinsic cues, such as metabolic (energy) and hormonal fluctuations.
For example, brown fat is characterised by its colour and capacity for fat burning, attributes derived from its high density of mitochondria—often called the ‘powerhouses of the cell’—which contain a high percentage of iron. Infants have a high level of brown fat, which diminishes with age. These adaptations illustrate fat cell plasticity, where cells transition between different functional states in response to environmental or physiological conditions.
Another example is pink fat cells emerge during pregnancy, lactation, and post-lactation as white fat undergoes a process called ‘pinking,’ transforming into milk-producing glandular structures. These structures, referred to as pink fat, support lactation. Unlike other fat types, pink fat is temporary; after lactation, it can revert to white fat. Additionally, brown fat in the mammary region can transition into myoepithelial cells of the areola, which help with milk ejection.
Fasting acts as an intrinsic cue, triggering hormonal signals like glucagon from the pancreas. This prompts the liver to release stored glucose (glycogen) into the bloodstream, ensuring a steady energy supply for the brain and body when dietary glucose is unavailable, such as during sleep or fasting.
Another intrinsic cue is nonshivering thermogenesis. This process is triggered by factors such as extreme temperatures, pollution, and physical exercise. Nonshivering thermogenesis is a way the body produces heat without shivering, primarily using brown fat, which generates warmth by burning energy rather than storing it.
Fat cells also respond to extrinsic cues, including diet, temperature extremes, and pollution. An example of an extrinsic cue affecting fat cell behaviour is exposure to extreme cold temperatures, which induces phenotypic plasticity; activating ‘beiging’ within white fat deposits.
Beige fat demonstrates comparable thermogenic capacity to brown fat. Meaning it can change function from white to beige to generate heat to help maintain body temperature and increase energy expenditure. This adaptation can play a role in regulating body weight and metabolic health.
Another example of an extrinsic cue is chronic overfeeding, which can reduce beige fat, transitioning back toward more energy-storing white fat in place of the energy-burning beige fat. During weight loss, the body initiates a process called lipolysis, breaking down stored triglycerides (fats) into free fatty acids (FFAs) and glycerol. Contrary to popular belief, most fat when ‘losing weight’ is lost as CO₂ through respiration, while a smaller portion is eliminated as water through sweat and urine.
Lipolysis also occurs during periods of rest, such as when we are sleeping, to sustain vital functions like breathing, circulation, and temperature regulation. It helps maintain cellular energy requirements, ensuring continuous support of essential metabolic processes during reduced physical activity.
Fat Cells and Insulin
Insulin is a hormone that acts by promoting blood sugar or glucose transport across the membrane of target fat cells, as well as muscle cells, liver cells and brain cells. Insulin acts on receptors in these cells, creating high-affinity insulin sensitivity or making the cells responsive to insulin. Activating a complex signalling network that triggers a cascade of signalling events.
By signalling, we mean chemical communications that influence the target cellular processes, such as how efficiently they uptake glucose into the cells, metabolic activity, and gene expression. Ultimately, insulin contributes to essential physiological functions including the regulation and management of blood sugar levels, energy homeostasis, and body weight. How?
Insulin plays a crucial role in metabolism by signalling fat cells to store fat. Significant disruption to this insulin receptor signalling network can result in insulin resistance, a condition in which the body doesn't respond well to the effects of insulin. As a result, the pancreas produces more insulin to overcome the resistance, leading to higher levels of insulin in the blood. Why is this a problem?
Insulin resistance is a problem for several reasons, primarily because it can lead to a variety of health issues, including type 2 diabetes, cardiovascular disease, and other metabolic syndromes. Here’s a breakdown of why insulin resistance is problematic:
Hyperinsulinemia: Hyperinsulinemia happens when you have a higher amount of insulin in your blood than what's considered normal due to insulin resistance. As the body becomes resistant to insulin, the pancreas compensates by producing more insulin. Elevated insulin levels (hyperinsulinemia) can themselves cause further health complications, such as high blood pressure, increased fat storage, and even alterations in heart and blood vessel function.
Type 2 Diabetes: If insulin resistance worsens, the pancreas may eventually fail to produce enough insulin to maintain normal blood glucose levels, leading to type 2 diabetes. This condition is characterised by high blood sugar levels, which can damage organs and tissues throughout the body.
Increased Fat Storage: Insulin promotes fat storage, particularly in the abdominal area. High insulin levels due to insulin resistance can lead to excess fat accumulation, contributing to obesity and further increasing the risk of metabolic syndrome.
Cardiovascular Disease: Insulin resistance is associated with a cluster of cardiovascular risk factors, including high cholesterol, high triglycerides, high blood pressure, and an increased risk of forming blood clots. These factors contribute to the development of atherosclerosis, a condition characterised by the hardening and narrowing of the arteries, which can lead to heart attacks and strokes.
Other Health Issues: Insulin resistance is also linked to an increased risk of certain cancers, non-alcoholic fatty liver disease, polycystic ovary syndrome (PCOS), and even Alzheimer’s disease.
Clinical and experimental evidence indicates that hyperinsulinemia can precede and promote both insulin resistance and obesity. This emphasises the significance of maintaining insulin sensitivity or requiring smaller amounts of insulin to lower blood glucose levels, as a critical aspect of the homeostatic control of energy balance and body weight. Homeostatic refers to the tendency towards a relatively stable equilibrium, between interdependent elements .
The homeostatic regulation of energy balance mandates the brain to uphold optimal energy levels. This is achieved by the brain continuously monitoring peripheral signals related to energy status and metabolism, triggering and managing feeding behaviours or food intake and various autonomic, and neuroendocrine (hormonal) factors that influence energy utilisation.
Fat Cells and Energy Homeostasis
Fat cells are involved in regulating the dynamic equilibrium between energy storage and energy expenditure or whole-body energy homeostasis. The hypothalamus deep inside the brain orchestrates this fine balancing act ,collaborating with other parts of the brain, as well as fat cells, gut microbiota, the pituitary gland, the liver and other systems to address metabolic fluctuations.
The Basal Metabolic Rate (BMR) is a crucial factor in this energy balance. A low BMR indicates a slower metabolism and predicts future weight gain. Conversely, a high BMR signifies a faster metabolism, requiring more calories to sustain daily functions. Some people may have a naturally higher or lower BMR based on their genetic makeup.
Mitochondria inside fat cells turn energy into a format called Adenosine Triphosphate (ATP). In the context of energy metabolism, ATP acts as the body's "energy currency," powering various cellular functions by releasing energy stored in its chemical bonds. Much like a rechargeable battery fuelling cell stability and overall bodily functions.
When glucose stores are low, this elicits low levels of insulin and increases mitochondrial respiration toward thermogenesis for fat burning, instead of ATP production. Leading to increased fat mobilisation in the bloodstream and energy expenditure. In this scenario, since our body does not have enough glucose to burn for energy, it burns fat instead.
As our body breaks down fat, it forms ketones, which take over from glucose as the main energy source for our brain and body. This shift, known as ketosis, can increase the metabolic rate of white fat, making it act more like brown fat or beige fat, burning fat for energy. While ketosis is a weight management approach, medical guidance is wise, as it may not be suitable for everyone and could have varying effects depending on one's health status.
In contrast, we know that brown fat, when exposed to high levels of insulin in situations of over-nutrition, behaves more like white fat, slowing metabolic rate and promoting fat storage over fat burning. This points to obesity as a disorder of the energy homeostasis system rather than simply arising from the passive accumulation of fat.
Dysregulated energy homeostasis impairs fat cell plasticity and disrupts the normal communication between the brain and body. This miscommunication hampers the regulation of appetite and satiety signals, leading to a vicious cycle of abnormal fat storage and altered signalling. Consequently, this perpetuates overeating, further disrupts energy balance, and contributes to ongoing weight gain
Fat Cells and Hormones
Fat cells function as an endocrine organ by producing hormone-like substances called adipokines or adipocytokines. These molecules play dual roles in the body: they have both pro-inflammatory and anti-inflammatory effects and are crucial in regulating whole-body energy homeostasis. Imbalances in adipokines can disrupt how the body manages energy expenditure and storage, leading to metabolic irregularities, including insulin resistance, obesity, type II diabetes, chronic inflammation and heart disease.
White fat produces and releases (or synthesises) different adipocytokines, including:
Leptin: predominantly pro-inflammatory, leptin does many things but is well known for regulating appetite by signalling the brain to alter food intake when fat stores are sufficient, regulating sensations of hunger and satiety and controlling energy expenditure. Leptin deficiency is associated with severe obesity, and high levels of leptin, seen in leptin resistance, are linked with chronic inflammation and metabolic disorders.
Adiponectin: predominantly anti-inflammatory and insulin-sensitising. It is one of the few adipokines that lowers inflammation and improves insulin sensitivity. Elevated levels of adiponectin are beneficial and associated with reduced risk of type 2 diabetes and cardiovascular diseases. However, paradoxically, elevated adiponectin levels have been linked with certain inflammatory conditions like arthritis and inflammatory bowel syndrome (IBS).
Adipsin: generally considered pro-inflammatory, and has a novel role as a regulator of bone marrow fat and, consequently, overall bone health. It also controls blood glucose levels and insulin sensitivity. High levels of adipsin is associated with increased fat mass and may contribute to cardiometabolic disease through promoting insulin resistance and inflammation.
Resistin: predominantly pro-inflammatory, is thought to influence weight regulation and glucose metabolism. High levels of resistin are associated with obesity and can lead to insulin resistance and inflammation. In turn, this can lead to systemic inflammation (throughout the body), linked with health issues, such as type II diabetes and heart disease.
Brown fat synthesises different adipocytokines, including:
Fibroblast Growth Factor 21: FGF21 is primarily anti-inflammatory helping regulate energy homeostasis through the control of glucose, fat, and energy metabolism. FGF21 induces the insulin-sensitising hormone adiponectin, so has been studied as a therapeutic agent for the treatment of obesity.
Interleukin-6: IL-6 can be pro-inflammatory in certain contexts and anti-inflammatory in others. It is a complex adipokine mediating innate and adaptive immune responses. As such, it plays a critical role in the body’s defence mechanism but can contribute to chronic inflammation which is linked to a range of conditions, including autoimmune diseases and metabolic syndrome.
Irisin: generally anti-inflammatory effects due to its role in enhancing the browning of white fat cells enhancing energy metabolism, increasing energy expenditure, regulating insulin use and so curbing fat accumulation. It can be stimulated through extreme temperatures (e.g., sauna), a high-fat diet (good fats), and HIT training, potentially offering protective effects against obesity and diabetes.
Tumor Necrosis Factor-alpha: TNF-α is strongly proinflammatory, involved in many physiological processes, including inflammation, cell differentiation, and cell death. TNF-α has been induced in models of diabetes and obesity, providing evidence for a functional link between inflammation and obesity. High levels of TNF-α are associated with inflammatory diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease, as well type 2 diabetes, where it contributes to insulin resistance and metabolic dysfunction.
These examples represent only a portion of the signalling hormones from fat cells, and their roles in whole-body energy homeostasis, that continue to be actively researched. Maintaining a balance of pro-inflammatory and anti-inflammatory adipocytokines is crucial for good health, while elevated pro-inflammatory adipocytokines are a feature of metabolic irregularities.
Fat Cells and Metabolism
Here we will briefly explore two dietary conditions affecting fat cell metabolism:
Condition 1: Meals that help maintain blood sugar levels
Diets low in simple carbohydrates, high in complex carbohydrates, rich in good fats, and with normal protein levels can significantly boost the metabolic rate of fat cells.
Condition 2: Meals that stimulate high blood sugar levels
Diets high in simple carbohydrates, low in complex carbohydrates, low in good fats, and with normal protein levels can have varying effects on fat cell metabolism, influenced by individual differences. Notably, persistent insulin spikes resulting from such diets may lead to increased fat storage and decreased energy availability in the blood.
In condition 2, persistent insulin spikes can trigger a perception of energy scarcity in the hypothalamus in the brain; the hypothalamus signals real-time energy scarcity in the bloodstream, despite sufficient glucose, fatty acids and glycogen stores. This can prompt an early return to hunger. Here’s an explanation of why this condition occurs and the mechanisms involved:
High Glycemic Foods and Insulin Spikes: Meals rich in simple carbohydrates (such as sugars and refined grains) cause rapid increases in blood glucose levels. In response, the pancreas secretes insulin to help cells absorb glucose from the bloodstream. This process is meant to regulate blood sugar levels.
Impact on Fat Storage and Energy Levels: When insulin levels are consistently high due to frequent consumption of high-glycemic foods, the body tends to store more glucose as fat rather than using it for immediate energy. This is because insulin not only facilitates glucose uptake into cells but also promotes fat storage.
Hypothalamic Response to Perceived Energy Levels: The hypothalamus, a critical brain region involved in regulating hunger and energy homeostasis, senses changes in energy availability. Despite the actual abundance of stored energy (glucose, fatty acids, and glycogen), high insulin levels can reduce the amount of glucose available in the bloodstream, as it is quickly moved into cells or converted into fat. This rapid decrease in blood glucose can be perceived by the hypothalamus as a state of energy deficiency.
Triggering Hunger Signals: Because the hypothalamus aims to maintain energy balance, it responds to perceived energy scarcity by triggering hunger signals. This encourages food intake to restore what it perceives as dwindling energy supplies, leading to a cycle where one may feel the need to eat again soon after a meal.
not just about reducing caloric intake, but also about making strategic nutritional choices that support insulin sensitivity and hormonal balance. By focusing on a diet rich in protein, fiber, and healthy fats, while managing carbohydrate intake through choices of complex or low glycemic options, individuals can stabilize blood sugar levels and avoid the sharp insulin spikes that contribute to fat storage and erratic hunger signals.
Intermittent fasting can also play a role by improving metabolic flexibility—the body's ability to switch between burning carbs and fats efficiently—which helps in maintaining insulin sensitivity. Regular physical activity complements these dietary strategies by enhancing muscle insulin sensitivity, accelerating energy expenditure, and promoting the release of hormones that favorably impact hunger and satiety.
Moreover, managing stress is crucial, as chronic stress can lead to elevated cortisol levels, worsening insulin resistance and disrupting eating patterns. Stress reduction techniques such as mindfulness, meditation, and adequate sleep can therefore support hormonal balance and aid in weight management.
Ultimately, long-term weight management involves a holistic approach that considers not only dietary and physical activity patterns but also hormonal health and emotional well-being. This comprehensive strategy supports sustained insulin sensitivity, optimises energy regulation, and aligns food-seeking behaviours with the body’s true nutritional needs, thereby promoting a healthier body weight and overall metabolic health.
Fat Cells as Immune Tissue
Fat cells, or adipocytes, house various types of immune cells within the adipose tissue. These immune cells include macrophages, dendritic cells, and lymphocytes (T and B cells), which play significant roles in maintaining tissue homeostasis and immune regulation. The presence of these immune cells within adipose tissue makes it a crucial component of the immune system.
Adipocytes produce adipocytokines (also known as adipokines), which we learnt are hormones that can influence systemic inflammation and immune responses. Some well-known adipokines include leptin, which regulates energy balance and has immunomodulatory properties, and adiponectin, which has anti-inflammatory effects.
In obesity, the adipose tissue undergoes significant changes, including hypoxia (low oxygen levels) and cellular stress, leading to a shift towards a more inflammatory state. This is characterised by an increased infiltration of pro-inflammatory immune cells and a higher production of pro-inflammatory cytokines, contributing to systemic inflammation.
This chronic, low-level inflammation associated with obesity is linked to various metabolic diseases, including insulin resistance, type 2 diabetes, and cardiovascular diseases. The balance between anti-inflammatory and pro-inflammatory forces within adipose tissue is crucial for maintaining metabolic health and overall well-being.
Fat Cells and Gut Microbiome
A growing body of evidence indicates a dynamic interplay between fat cells and the gut microbiome. Gut microbiota can influence the metabolic functions of the body, including those related to adipose tissue, through various mechanisms such as inflammation and hormone regulation.
Diets low in carbohydrates have been shown to influence specific bacterial strains like Bacteroidaceae Bacteroides, contributing to effective body weight reduction. Similarly, a ketogenic diet can impact the presence of beneficial bacteria strains like A. Muciniphila and Lactobacillus, crucial in regulating lipid metabolism and weight. These are well-documented phenomena
The relationship between the gut microbiota and fat cells extends beyond diet, responding to factors like temperature, intermittent fasting, and caloric restriction. Fat-derived leptin and adiponectin can alter microbial composition and function, which in turn affects metabolic health. by modulating inflammation, immune responses, metabolism, and communication pathways.
A growing number of evidence suggests that gut microbiota play essential roles in fat cell inflammation in obesity and related disorders. Changes in the abundance and diversity of microbiota are associated with inflammation in obesity. Additionally, some probiotic bacteria like Bifidobacterium genera added to foods and medicines can regulate gut microbiota and fat metabolism.
Other probiotic bacteria such as Lactobacillus paracasei, Akkermansia muciniphila, Faecalibacterium prausnitziiare, Parabacteroides distasonis and Clostridium leptum, have been reported to improve insulin sensitivity and alleviate the inflammation of fat cells. These probiotics are being investigated for their potential benefits in managing obesity and metabolic diseases.
Despite these associations, the causal pathways and the mechanisms underlying the relationship between fat cells and gut microbiota have yet to be fully classified, acknowledging the complexity and ongoing research in understanding exactly how the gut microbiota interacts with host metabolism at a detailed mechanistic level.
Fat Cells Revisited
Fat cells emerge as a crucial factor influencing whole-body homeostasis. Understanding the intricacies of fat cell biology is crucial in addressing the surge of inflammation-driven diseases, offering insights into conditions like obesity and type II diabetes. This knowledge provides a systemic approach to exploring fat cells within this rapidly expanding realm of research.
Plasticity: fat cells exhibit plastic properties, responding through changes in energy balance and colour, impacting metabolic activity and fat cell structure and function;
Insulin: Insulin is a peptide hormone with a role in supporting the uptake of blood sugar or glucose into fat cells (and other cells). Prolonged elevated blood sugar can lead to insulin resistance, affecting how fat is stored and used;
Energy Homeostasis: fat cells are a central metabolic organ in the regulation of whole-body energy homeostasis. Acting as an energy bank, storing and releasing energy is just one role of the highly dynamic fat cells;
Hormones: fat cells are metabolically active and produce various hormones and signalling molecules called adipocytokines, such as leptin and adiponectin, that play a significant role in hunger, satiety and levels of systemic inflammation;
Metabolism: Fat cells and blood lipids respond differently to various diets based on the composition and nutritional content of those diets. Individual responses to these diets can vary based on factors like metabolism and genetics;
Immune System: The interplay between fat cells, fat cell immune cells, immune cells, adipocytokines, and the gut microbiome significantly regulates inflammation in the brain and body;
Gut Microbiome: Cross-talk between fat cells and the gut microbiome influences fat cells in many different ways and vice versa, by regulating appetite, energy absorption, fat storage, and chronic inflammation, also mood;
Fat-Brain Axis: Chemical communication between fat cells and the brain, known as the "fat-brain axis," influences appetite, satiety, energy metabolism, and mood.
The content presented in this blog incorporates evidence-based information along with perspectives and opinions. It is designed to stimulate discussions and explorations of emerging research. However, it does not represent official advice or exhaustive factual claims. The goal is to offer readers valuable insights on particular topics of interest while respecting the boundaries of objectivity and subjectivity. Alternative viewpoints are highly encouraged and welcomed at Blindspot. Readers of course consider multiple sources when forming their opinions.