E l adipose tissue is a specialized connective tissue in lipid storage . It can be considered a somewhat atypical connective tissue since it has very little extracellular matrix, but its embryonic origin is the mesenchymal cells derived from the mesoderm, which also give rise to the rest of the connective tissues. Adipose tissue is present in all mammals and in some non-mammalian animal species. Your ability to store lipids depends on your cells, the adipocytes , which can contain large drops of fat in your cytoplasm. Fat is a good store of energy since it has about twice the caloric density of sugars or proteins. These warehouses are used to provideenergy molecules to other tissues or to directly generate heat. Adipocytes clump together in large numbers to form adipose tissue, although they can also be found dispersed in loose connective tissue. After adipose tissue, the liver is the second structure that stores the most lipids in lipid drops.
Adipose tissue is a highly dynamic endocrine organ capable of secreting bioactive factors known as adipokines that regulate a wide variety of biological functions. Traditionally, two types of adipose tissue have been distinguished based on their morphological and functional characteristics: white and brown adipose tissue (Figure 1). The adipocytes of white adipose tissue are large rounded cells (25-200 mm) characterized by a large unilocular lipid droplet surrounded by a thin layer of cytoplasm, few mitochondria, and a flat nucleus displaced to the periphery. The main functions of white adipose tissue are the accumulation of energy in the form of triacylglycerols, thermal insulation and the secretion of adipokines that regulate various biological processes in an autocrine, paracrine and endocrine way. As discussed in a previous article, brown fat adipocytes are smaller cells (15-60 mm) and have a polygonal shape, multilocular lipid droplets, multiple mitochondria, and a central nucleus. Adaptive thermogenesis by activating UCP1 constitutes the main biological function of brown fat, which can also act as a deposit of triacylglycerols and secrete adipokines, although to a lesser extent than white adipose tissue.
In 2010, the existence of a third type of fat cells called beige adipocytes with morphology of brown adipocytes inside white adipose tissue was described ( Figure 1 ). Acquisition of this phenotype similar to brown adipocytes (presence of multilocular lipid droplets and a large number of mitochondria) occurs after exposure to cold, stimulation of b-adrenergic receptors or by the treatment of agonists of the g receptor activated by the factor g peroxisome proliferator (PPARg), in a process called adipose tissue browning (“ fat browning ”). After induction, beige adipocytes express classical thermogenic genes ( UCP1, PPARGC1A, DIO2 and ADRB3), but they also express differential gene markers such as CD137, TMEM26, TBX1 or SHOX2 . The fat browning phenomenon could have great clinical relevance, since studies carried out in rodents have shown that activation of beige adipocytes is associated with resistance to obesity and associated metabolic disorders.
Inflammation and fibrosis of adipose tissue
Obesity is a state of low-grade chronic inflammation. In this sense, the pathological expansion of adipose tissue in obesity is accompanied by an increase in the recruitment of macrophages and other cells of the immune system, an increased secretion of proinflammatory adipokines, as well as alterations in the components of the extracellular matrix of adipose tissue. , which aggravate the systemic inflammation of obese individuals.
Under physiological conditions, adipose tissue-resident Th2 and Treg CD4 + eosinophils and lymphocytes suppress inflammation by secretion of anti-inflammatory cytokines, such as IL-4, IL-10, or IL-13, which activate the anti-phenotype. Inflammation of M2 macrophages ( Figure 3). However, excess adiposity favors the infiltration of macrophages, neutrophils, foam cells, T and B lymphocytes, mast cells, and dendritic cells in adipose tissue. A characteristic feature of inflammation associated with obesity is the macrophage polarization towards a proinflammatory M1 profile, as well as the transformation of the anti-inflammatory lymphocytes ¥ 2 and CD4 + Treg into inflammatory cells ¥ 1 and ¥ 17, particularly in fat visceral. Another histological feature of inflammation of adipose tissue is the increased apoptosis of adipocytes, which are surrounded by macrophages, forming a crown-like structure. The adipocytes themselves favor this inflammatory microenvironment by secreting proinflammatory cytokines, chemokines, and alarmins.
Obese subjects present a lower production of elastin and an increase in the synthesis of type I, III, V and VI collagen, fibronectin and laminin in adipose tissue, which favor the appearance of fibrotic areas in this tissue, being more abundant in the visceral fat than subcutaneous fat. This alteration in the remodeling of the extracellular matrix decreases the flaxibility of the adipose tissue, contributing to the dysfunction and inflammation of the adipose tissue. Likewise, the fibrosis of the adipose tissue limits its capacity for expansion, a fact that favors the ectopic accumulation of lipids in other peripheral tissues, such as the liver, pancreas, skeletal muscle or heart, generating a phenomenon called lipotoxicity. In this sense, obesity is associated with increased lipolysis, especially in the visceral fatty deposit. Liver overload with excess fatty acids inhibits insulin and apoliprotein B degradation and increases hepatic gluconeogenesis and lipoprotein metabolism in hepatocytes. Therefore, fibrosis of adipose tissue contributes indirectly to the development of hyperinsulinemia, hyperglycemia and dyslipidemia associated with visceral obesity. Furthermore, the stiffness of adipose tissue is associated with an increase in markers of hepatocellular damage, as well as with a greater development of steatosis and liver fibrosis. hyperglycemia and dyslipidemia associated with visceral obesity. Furthermore, the stiffness of adipose tissue is associated with an increase in markers of hepatocellular damage, as well as with a greater development of steatosis and liver fibrosis. hyperglycemia and dyslipidemia associated with visceral obesity. Furthermore, the stiffness of adipose tissue is associated with an increase in markers of hepatocellular damage, as well as with a greater development of steatosis and liver fibrosis.
Altered adipokine secretion
Since the discovery of the hormone leptin in 1994, adipose tissue has emerged as an endocrine organ capable of secreting hormones, cytokines, growth factors, and other bioactive peptides, encompassed under the name of adipokines. Today, it is well known that these adipokines not only act autocrine / paracrine on adipocytes, but also exert endocrine actions, regulating biological functions as diverse as appetite control, glycidic and lipid metabolism, cardiovascular homeostasis, or reproduction, among others ( Table 1). There is a relevant group of adipokines involved in the regulation of the immune system and inflammation represented by acute phase reactants (C-reactive protein or serum amyloid protein A), cytokines (tumor necrosis factor a [TNF-a] or interleukin 6 [IL -6]), chemokines (monocyte chemotactic protein 1 [MCP-1]), alarmins (HMGB1, tenascin C or calprotectin), inflammatory factors (leptin or osteopontin) and anti-inflammatory factors (adiponectin or lipocalin-2). In this sense, obesity is associated with a greater increase in the secretion of pro-inflammatory adipokines, as well as a repression of the anti-inflammatory hormone adiponectin, which favors the development of systemic inflammatory responses and metabolic dysfunction.
Extensive scientific evidence has demonstrated differences in the expression and secretion of adipokines in visceral and subcutaneous fatty deposits, a more pronounced inflammatory secretory profile in visceral fat in obese patients. Altered adipokine secretion in obesity constitutes an important mechanism for the development of insulin resistance, dyslipidemia, and cardiovascular complications observed in the context of obesity.
Decrease in the mass and / or activity of brown and beige fat
Brown fat represents a small fraction of the total adiposity (~ 0.1%), but it has a great capacity to dissipate energy by clearing free fatty acids, consuming glucose and generating heat during the thermogenesis process. The activity of brown fat can be induced in response to cold and by activation of the sympathetic nervous system. Likewise, the activity of brown fat is greater in women than in men, and presents a progressive decline with age. For all the above, the mass and / or activity of brown fat determines the energy balance.
The discovery of brown and beige fat in adult individuals has opened a wide field of research focused on these tissues as a potential therapeutic target for developing anti-obesity drugs, given the thermogenic capacity of both fatty deposits. The interscapular region exhibits increased expression of a classic brown adipocyte marker, ZIC1 , while the supraclavicular region exhibits increased expression of the beige adipocyte marker TBX1 , suggesting that different populations of brown and beige adipocytes in these anatomical regions may respond differentially to external stimuli, constituting different potential targets for therapeutic interventions.
In recent years, it has been shown that obese patients present a reduction in the size and / or activity of brown and beige fatty deposits, which could contribute to the development of deleterious complications of obesity. In this sense, an inverse correlation has been observed between brown fat and total adiposity, BMI and fasting blood glucose.
CONCLUSION
Weight gain is associated with inflamed, fibrotic, and dysfunctional adipose tissue that favors ectopic fat accumulation and insulin resistance. Likewise, the reduction of the mass and / or activity of the brown and beige fatty deposits in situations of excess adiposity contribute to the development of comorbidities associated with obesity. Therefore, the evaluation of body composition is absolutely recommended for the diagnosis, treatment and monitoring of overweight and obese patients. In visceral obesity patients, a 5-10% reduction in body weight induces an increase in insulin sensitivity, an improvement in the lipid profile and a reduction in proinflammatory factors, thus reducing the risk of developing cardiometabolic diseases.
