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 influence to gain insights into their profound effects 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?
On average, a human adult has 30-40 billion fat cells. 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 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 is the most common, and white fat can transdifferentiate to brown fat, beige fat, and pink fat!
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 play a role.
What do you mean by environment?
E.g., where we live, what, when and how often we eat, pollution, substance use, sleep, exercise, stress and light levels, circadian clock, and temperature extremes.
Starting as we mean to go on
Adipocytes or fat cells, play a pivotal role that goes beyond storing excess energy. Yet they frequently endure undue scrutiny, often associated with obesity, a complex condition that has been oversimplified. 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.
We know that fat cells’ influence extends to our mental and physical well-being, impacting us in positive and challenging ways, depending on different factors. A blend of biopsychosocial factors, including genetics, physiology, emotions, cognition, and the environment can influence them. Recognising their complexity and intricate interplay with these factors is crucial for understanding their contribution to our immune (defence), endocrine (hormones), and metabolic (energy) systems.
"The Secret Life of Fat Cells" highlights their multifaceted functions, discreetly playing a pivotal role in regulating whole-body energy balance, modulating immune responses, attenuating inflammation, and synthesising hormones. This blog aims to offer insights into the crucial role that fat cells play in sustaining the delicate equilibrium of our physical, and mental health, and overall well-being
Fat Cell ‘Plasticity’
Fat cells display plasticity properties, meaning they can change in function and structure (size, shape, and number). They can also transdifferentiate into different cell types in response to intrinsic cues from within the body, such as metabolic and hormonal fluctuations. Fat cells also respond to extrinsic cues from outside the body, such as diet, temperature extremes and pollution.
Obesity is influenced by external factors like nutrition choices, stress levels and genetics. When these factors lead to obesity, it acts as an extrinsic cue, signaling fat cells to change. These changes can include existing cells getting larger (hypertrophy) and/or multiplying in number (hyperplasia). Additionally, new fat cells can form known as adipogenesis.
Another example of an extrinsic cue affecting how fat cells behave is exposure to extreme cold temperatures, which signals white fat to transdifferentiate into brown fat. Brown fat has thermogenic properties, meaning it generates heat to help maintain body temperature and increase energy expenditure. This adaptation can play a role in regulating body weight and metabolic health.
It is the case that we do not ‘lose fat cells’ when we change habits around diet, fasting and exercise, rather they shrink. The body initiates a process known as lipolysis, breaking down stored fats or lipids into free fatty acids and glycerol. These components are then released into the bloodstream, with some stored in the liver and the majority expelled through our breath (CO2), also 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 even during reduced physical activity.
Fasting serves as an intrinsic cue, triggering hormonal signals like glucagon from the pancreas, which signal the liver to release stored glucose (glycogen) into the bloodstream. This ensures that our brain and body have a steady supply of glucose for energy while we are sleeping or when dietary glucose intake is reduced.
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.
Other intrinsic cues can manifest in distinct colour changes in fat cells, such as the emergence of pink fat during pregnancy and lactation. These dynamic alterations in colour represent a unique aspect of fat cell plasticity. Brown fat gets its colour and propensity for fat burning from its density of mitochondria, often referred to as the ‘powerhouses of the cell’ containing a high percentage of cellular iron.
An imbalance in energy homeostasis can lead to the transdifferentiation or reconfiguration of brown fat to take on white fat traits. Whereby, brown fat can transdifferentiate from being metabolically active with thermogenic capacity, to more storage-oriented white fat. And the reverse is true, where white fat can behave more like brown fat through a process called ‘beiging’.
Beiging can occur under certain conditions, such as chronic cold exposure, fasting, and particular exercise (HIT endurance training). In these scenarios, beige fat demonstrates comparable thermogenic capacity to brown fat, switching phenotype or traits from previously being white fat storage to fat-burning brown fat.
Pink fat cells are modelled only during pregnancy, lactation, and post-lactation. White fat remodels through a process called ‘pinking’, transdifferentiating to milk-producing glands which can be defined as pink fat. Pink fat can change into brown fat, and brown fat during pregnancy and lactation transforms into myoepithelial cells of the areola (darker area around the nipple).
This plasticity is specialised and temporary to support breastfeeding. After the lactation period ends, myoepithelial cells revert to their previous form, which is brown fat. So, these specialised changes are reversible; brown fat cells can return to releasing energy as needed for temperature control, similar to their function before pregnancy and lactation.
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, also metabolism, and gene expression. Ultimately, insulin contributes to essential physiological functions including the regulation and management of blood sugar levels, energy homeostasis and body weight.
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 so the pancreas makes more insulin to overcome the resistance, leading to higher levels of insulin in the blood.
Clinical and experimental evidence indicates that hyperinsulinemia can precede and promote both insulin resistance and obesity. Hyperinsulinemia happens when you have a higher amount of insulin in your blood than what's considered normal due to insulin resistance.
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, 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 fueling 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, burning fat for energy.
In contrast, we know that brown fat, when exposed to high levels of insulin in situations of overnutrition, 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 limits fat cell plasticity, and diminishes the normal cues between brain and body that among other things, would orchestrate balanced appetite and satiety. Creating a vicious circle of abnormal fat storage and altered signalling, perpetuating a cycle of overeating, further disruption of energy balance, and weight gain.
Fat Cells and Hormones
Fat cells act as an endocrine organ, producing hormone-like molecules known as adipokines or adipocytokines. These molecules have dual roles of pro-inflammatory and anti-inflammatory, and regulating whole-body energy homeostasis. Imbalances in these hormones can affect how the body expends energy and stores energy.
White fat produces and releases (or synthesises) different adipocytokines, including:
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 has a relationship with severe obesity.
Adiponectin: has both anti-proinflammatory and insulin-sensitising properties. It helps improve the body's response to insulin and reduces inflammation. However, elevated levels of adiponectin are positively associated with inflammatory conditions such as arthritis and IBS.
Adipsin: 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. However, adipsin may link increased fat mass and dysregulated fat cells with cardiometabolic diseases.
Resistin: Resistin is thought to influence weight regulation and glucose metabolism. Elevated levels of resistin in obesity can lead to insulin resistance and inflammation. In turn, this can lead to low-level systemic inflammation throughout the body, linked with health issues.
Brown fat also synthesises different adipocytokines, including:
Fibroblast Growth Factor 21: FGF21 helps 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 is a complex adipokine with both anti-proinflammatory properties. IL-6 mediates innate and adaptive immune responses, which if dysregulated can amplify inflammation and a switch from an acute to a chronic inflammatory state.
Irisin: Irisin is involved in enhancing the browning of white fat cells improving systemic metabolism, increasing energy expenditure, regulating insulin use and so curbing fat accumulation. It can be stimulated through extreme temperatures, a high-fat diet (good fats), and HIT training.
Tumor Necrosis Factor-alpha: TNF-α is a proinflammatory adipokine of fat cells, 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.
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-anti-inflammatory adipocytokines is crucial for good health, while elevated pro-inflammatory adipocytokines are a feature of obesity and related conditions.
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 the highest 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 decreased energy availability in the blood.
In condition 2, persistent insulin spikes can promote fat storage and 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.
The impact of insulin spikes on the overall availability of energy in the body highlights its practical implications for maintaining a balance in the body's energy regulation (homeostasis) and weight management. Prioritising protein, complex or low glycemic carbohydrates, healthy fats, intermittent fasting, and stress reduction can effectively manage insulin sensitivity.
Long-term weight management involves enhancing insulin sensitivity or maintaining insulin levels within a 'normal' range. Fat cells thrive when insulin levels are sensitive or normal, renewing satiety signals and aligning food-seeking behaviours with the body's actual needs.
Fat Cells as Immune Tissue
Fat cells have their own immune cells. These immune cells are an integral part of the adipose tissue and play a crucial role in maintaining the health and function of the fat cells. Immune cells living in the fat tissue, such as macrophages, dendritic cells, and T and B cells12, also help regulate immune processes.
Fat cells are also like mini-factories that produce various substances, including hormones called adipocytokines. These hormones can send signals to other parts of the body and influence many processes, including our overall inflammation levels and immune response.
When a person becomes overweight or obese, the fat cells can become stressed and start to function abnormally. This can cause the immune cells in the fat tissue to become overactive and produce elevated levels of pro-inflammatory adipocytokines. If prolonged, this can lead to a state of chronic, low-level inflammation in the brain and body.
This inflammation can spread and affect many other systems in the body, leading to various health problems, including insulin resistance. The interaction between fat cells and their resident immune cells and the immune system is a delicate balance and plays a crucial role in overall health.
Fat Cells and Gut Microbiome
We are including the relationship between fat cells and the gut microbiome, recognising that a growing body of evidence indicates a dynamic interplay that goes beyond a simple dual influence. The communication between the gut microbiota and fat cells is complex, with different avenues of impact.
On one hand, the gut microbiota and its metabolites respond to poor dietary choices, influencing the expansion, inflammation, and insulin resistance of fat cells. While diets rich in saturated fats can contribute to dysbiosis, or alter the balance of the gut microbiota.
On the other hand, varied diets, such as a low-carbohydrate diet, 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 like A. Muciniphila and Lactobacillus, crucial in regulating lipid metabolism and weight.
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 impact the composition of the gut microbiota 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.
Despite these associations, the causal pathways and the mechanisms underlying the relationship between fat cells and gut microbiota have yet to be fully classified.
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 the rapidly expanding realm of research.
Plasticity: fat cells exhibit plastic properties, responding to changes in energy balance and colour, impacting metabolic activity and fat cell 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 role in hunger, satiety and levels of 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.
Fat-Brain Axis: Chemical communication between fat cells and the brain, known as the "fat-brain axis," influences appetite, satiety, and energy metabolism.
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.