ADIPOSE (FAT) TISSUE
AS AN ENDOCRINE ORGAN
A MAJOR REASON WHY WEIGHT LOSS
CAN BE SO DIFFICULT FOR SOME
If you cruise on over to PubMed and type in the words, "Adipose Tissue as an Endocrine Organ," you'll find hundreds of studies bearing that exact name or similar. For instance, you'll learn that when it comes to this topic.....
- THIS IS NOT NEW INFORMATION: Fifteen years ago, a 2002 study from Clinical Endocrinology and Metabolism (Adipose Tissue as an Endocrine Organ) stated simply that, "Adipose tissue is a highly active endocrine organ secreting a range of soluble products with both local and distant actions. These hormones have important roles in metabolism, reproduction, cardiovascular function and immunity." Please be aware that any time you see the word "immunity" or variations thereof associated with adipose tissue, it is likely talking about its relationship to the chemicals / compounds we refer to collectively as INFLAMMATION.
- ADIPOSE TISSUE IS PART OF YOUR IMMUNE SYSTEM: In March of 2015, the journal Obesity (Adipose Tissue as an Immunological Organ) dealt with this issue. "This review will focus on the immunological aspects of adipose tissue and its potential role in development of chronic inflammation that instigates obesity-associated co-morbidities. Adipose tissue is a large immunologically active organ during obesity that displays hallmarks of both and innate and adaptive immune response. The adipose tissue of obese subjects becomes inflamed and contributes to the development of insulin resistance, type 2 diabetes and metabolic syndrome. Numerous immune cells including B cells, T cells, macrophages and neutrophils have been identified in adipose tissue, and obesity influences both the quantity and the nature of immune cell subtypes which emerges as an active immunological organ capable of modifying whole body metabolism through paracrine and endocrine mechanisms. Overwhelming evidence suggests that prolonged adipose tissue remodeling in response to caloric excess leads to chronic inflammation at the expense of reduced insulin-sensitivity." You get the point. Adipose tissue is seriously inflammatory. The biggest group of these inflammatory markers are collectively referred to as "adipokines".
- ADIPOKINES ARE CELLULAR CYTOKINES (MESSENGERS) THAT COME FROM FAT CELLS: In 2010, July's Molecular and Cellular Endocrinology (The Development and Endocrine Functions of Adipose Tissue) concluded, "Classically known for storing the body's fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and immune systems and play major roles in metabolism. Numerous studies have shown nutrient or hormonal manipulations can greatly influence adipose tissue development. In addition, the associations between various disease states, such as insulin resistance and cardiovascular disease, and disregulation of adipose tissue seen in epidemiological and intervention studies are great. Evaluation of known adipokines suggests these factors secreted from adipose tissue play roles in several pathologies." The previous link talks a bit about cytokines. As you might suspect, adipokines are the cytokines that come from adipose tissue.
A brief note about cytokines. Cytokines are small proteins secreted and released by cells or tissues to have specific effects on the interactions and communications with other cells or tissues --- sometimes quite distantly. Ten years ago, an issue of International Anesthesiology Clinics (Cytokines, Inflammation and Pain) concluded that, "There is significant evidence showing that certain cytokines/chemokines are involved in not only the initiation but also the persistence of pathologic pain by directly activating nociceptive sensory neurons. Certain inflammatory cytokines are also involved in nerve-injury/inflammation-induced central sensitization, and are related to the development of contralateral hyperalgesia/allodynia." The two cytokines most associated with ALLODYNIA / HYPERALGESIA (sometimes called hyperalgia) as well as CENTRAL SENSITIZATION are also two of the most common --- the two that will come up repeatedly today ---- Interleukin six (IL-6) and Tumor Necrosis Factor Alpha (TNF-α). The study went on to talk about the way these particular cytokines trigger GLIAL CELLS and MICROGLIA.
- ADIPOSE IS INFLAMMATORY: Although you've been given a taste of this, I could literally have put dozens upon dozens of studies under this bullet point. A Spanish study from a 2016 issue of Molecular and Cellular Endocrinology (Role of Bioactive Lipid Mediators in Obese Adipose Tissue Inflammation and Endocrine Dysfunction) said, "Special emphasis is given to polyunsaturated fatty acids of the omega-6 and omega-3 families and their conversion to bioactive lipid mediators through the cyclooxygenase and lipoxygenase pathways. The participation of omega-3-derived lipid autacoids in the resolution of adipose tissue inflammation... is also thoroughly discussed." What this means is that the fats that you consume are creating mediators (adipokines) that are either driving your body toward inflammation and pathology or away from inflammation and pathology (HERE). Speaking of pathology...
- ADIPOKINES ASSOCIATED WITH PATHOLOGY: Although we see it in most of these bullets, the German journal Internist spelled it out in 2014 study called --- you guessed it ---- Adipose Tissue as an Endocrine Organ. The authors stated, "With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines) changes towards a proinflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity and chronic inflammation......" Remember this; LOCAL INFLAMMATION is a critical part of any healing process. However, SYSTEMIC INFLAMMATION always creates pathological healing processes, namely because inflammation always leads to fibrosis (scar tissue) --- HERE. This is a big deal because fibrosis is the leading cause of death here in America (HERE).
- ADIPOKINES ARE RELATED TO CANCER: The journal Hormone Molecular Biology and Clinical Investigation devoted their July, 2015 issue to the subject of CANCER as it relates to adipose tissue, publishing some freaky studies on BREAST CANCER among others. One of these studies ---- Adipose Tissue, Obesity and Adipokines: Role in Cancer Promotion ---- concluded that, "Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose-related disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipokines and cancer risk. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis." I have talked about this via several posts in two different forms --- the first being the most obvious in relationship to this study (HERE), but the second (HERE) being the most important.
- ADIPOSE REGULATES GROWTH, PUBERTY, & METABOLISM: A study from the 1999 issue of the Soviet journal Biochemistry (Adipose Tissue as an Endocrine Organ Regulating Growth, Puberty, and other Physiological Functions), published a study on adipokines, most of which pertained to the adipokine Leptin as related to the study's title. Last December, the Journal of Endocrinology published a fantastic overview of today's topic called Adipose Tissue in Control of Metabolism. In it they concluded, "Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through its subtle functions at both organ and systemic levels. On one hand, adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body. On the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipokines that communicate with other organs and modulate a range of metabolic pathways. Therefore, adipose tissue dysfunction plays a prominent role in the development of obesity and its related disorders such as insulin resistance, cardiovascular disease, diabetes, depression and cancer. In this review, we will summarize the recent findings of adipose tissue in the control of metabolism, focusing on its endocrine and thermogenic function. An enormous amount of evidence has demonstrated that impaired biosynthesis, assembly, secretion and signalling transduction of adipokines are associated with the development of obesity and its related disorders." Think about it folks; this was a 20th century study.
- NOT ALL FAT IS THE SAME: The June 2006 issue of Diabetes (Adipose Tissue: From Lipid Storage Compartment to Endocrine Organ) revealed that, "Our understanding of how cellular events in the adipocyte affect the local environment and how systemic effects are achieved through endocrine interactions is rudimentary. While storage and release of lipids are major functions of adipocytes, the adipocyte also uses specific lipid molecules for intracellular signaling and uses a host of protein factors to communicate with essentially every organ system in the body. The intensity and complexity of these signals are highly regulated, differ in each fat pad, and are dramatically affected by various disease states." What I really want you to notice here is that different fat pads (the fat found in different parts of your body) are very different from each other. For instance, BELLY FAT is going to be quite different metabolically than the fat on the bottoms of your feet.
- MALE ADIPOSE IS DIFFERENT THAN FEMALE ADIPOSE: Last month's issue of Redox Biology published a study whose title tells the whole story --- Sex Matters: The Effects of Biological Sex on Adipose Tissue Biology and Energy Metabolism --- in which the authors concluded, "Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders." And on a similar note.....
- ADIPOSE AND REPRODUCTIVE FUNCTION, ESTROGEN, TESTOSTERONE: A 2010 issue of Fertility and Sterility (Adipose Tissue and Reproduction in Women) showed us that it's not just the fat itself that affects reproduction (for instance, women won't get pregnant if they fall below a certain percentage of body fat) but it's distribution (where it's found). In other words, too much adipose in general can lead to problems, but Belly Fat can be a deal-breaker for any number of physiological processes and HOMEOSTASIS. "Adipose tissue is a key endocrine organ involved in multiple processes, including glucose homeostasis, steroid production, immunoregulation, hematopoesis, and reproduction. The distribution of adipose tissue may also have a significant impact on reproductive function." Beyond this, I've shown you how Belly Fat affects both estrogen and testosterone and vice versa (HERE and HERE) in ways that can be worse than freaky.
- ADIPOSE TISSUE ALLOWS ORGANS TO COMMUNICATE WITH EACH OTHER: Oxford's journal Acta Physiologica (Adipose Tissue and its Role in Organ Crosstalk) gave us a basic yet informative abstract. "Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines." BTW, there were tons of studies on this topic --- especially concerning the way that the heart and cardiovascular system are affected by adipokines (usually adversely).
- ADIPOSE COMMUNICATES WITH YOUR CNS: The March 2016 issue of the Journal of Neuroinflammation took this idea a bit further in a study called Secret Talk between Adipose Tissue and Central Nervous System via secreted factors—an emerging frontier in the neurodegenerative research. "Adipokines are Not only Produced by the white adipose tissue but can also be expressed in the central nervous system [brain & cord] where receptors for these factors are present. When produced in periphery and to affect the CNS, these factors may either cross the blood brain barrier (BBB) or modify the BBB physiology by acting on cells forming the BBB. Adipokines could regulate neuroinflammation and oxidative stress which are two major physiological processes involved in neurodegeneration and are associated with many chronic neurodegenerative diseases." The authors even went on to talk about LEAKY BRAIN SYNDROME --- a topic I have discussed at length that is on some level, related to LEAKY GUT SYNDROME. "For instance, studies established positive correlations between mid-life adiposity in women with disruption of BBB integrity, showing that overweight/obesity could favor the onset of vascular disorders increasing BBB permeability later in life. In the same line of evidence, rats fed with Western diet, known for promoting diabetes and obesity, display a leakier BBB due to the decreased expression of tight junctions." If you want to see some of the science behind today's subject, simply take a look at this free study. Amazing proof that what you eat matters (even though your doctor is probably NOT WARNING YOU).
- ADIPOSE COMMUNICATES WITH YOUR HPA-AXIS: This study is so important, I am going to leave you with just a single sentence of the abstract. In similar fashion to the post I did last week where we learned that adipose tissue generates significant amounts of estrogen (a definite factor in ESTROGEN DOMINANCE and HORMONE DISRUPTION), we now see that adipose manufactures the stress hormone CORTISOL as well. The February 2014 issue of Hormone Molecular Biology and Clinical Investigation (Cross-Talk Between Adipose Tissue and the HPA Axis in Obesity and Overt Hypercortisolemic) stated that, "adipose tissue is also able to generate cortisol from cortisone." In other words, not only can your hormones make you fat, but fat itself creates some of these very hormones. Talk about a vicious cycle!
- ADIPOSE AND LACK OF TISSUE OXYGENATION: Lack of OXYGEN ("hypoxia") is common in adipose tissue as confirmed up by dozens of studies. Here are a couple. A 2008 issue of the British Journal of Nutrition (Hypoxia in Adipose Tissue: A Basis for the Dysregulation of Tissue Function in Obesity?) stated, "Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models. Cell-culture studies on murine and human adipocytes show that hypoxia (induced by low O2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor... It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases." Five years later, a 2013 copy of Physiological Reviews (Hypoxia and Adipose Tissue Function and Dysfunction in Obesity) concluded that, "There is substantial evidence that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of over 1,000 genes [this is a prime example of EPIGENETICS]. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity." How do you prevent hypoxia? Don't SMOKE, maintain a normal weight, and exercise (breathe hard) regularly.
As you can see, carrying around too much fat --- especially in the midsection --- has the potential to open Pandora's Box, releasing the adipokines, inflammation, and subsequent fibrosis related to numerous disease processes. If you follow some of the links on this page (especially hormonal and endocrine disruptor stuff), you can see why losing weight for some of you has been nigh impossible. To be successful you'll have to address this problem from many angles. The super cool thing is that the underpinning of most of these angles is the same thing. HERE is is, free of charge to you.