Adipose Tissue

Adipose tissue is a specialized type of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. Multiple hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview, growth factors, and cytokines are expressed by adipocytes and their associated stromal cells and macrophages. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Brown adipose tissue is present mostly in the fetus and in young children, and its main purpose is thermogenesis. Small deposits of brown adipose tissue persist into adult life. White adipose tissue is the major adipose tissue in adults, and it plays a role in several disease states, most notably obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome, and type 2 diabetes.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Adipose tissue is a type of loose connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue composed mainly of cells called adipocytes.

Composition

  • Adipocytes 
  • Stromal vascular fraction (SVF):
    • Preadipocytes
    • Fibroblasts
    • Vascular endothelial cells
    • Immune cells (major—adipose tissue macrophages)

Types of adipose tissue

Two classic types:

  • White adipose tissue:
    • Predominant type in adults
    • Major source of energy, stored as triglycerides
    • Contain single large lipid droplet (unilocular)
  • Brown adipose tissue:
    • Brown color due to increased vascularity and more mitochondria
    • Present in large amounts during fetal life (~ 5% of body mass of newborn Newborn A neonate, or newborn, is defined as a child less than 28 days old. A thorough physical examination should be performed within the first 24 hours of life to identify abnormalities and improve outcomes by offering timely treatment. Physical Examination of the Newborn)
    • Persists into adult life in much smaller amounts
    • Contains a large amount of small lipid droplets (multilocular)
    • Generates body heat

3rd, recently described, transitional type:

  • Beige, “inducible,” or “brite” (= “brown in white”) adipose tissue
  • Transitional/transformation phase, when white adipose tissue converts to brown adipose tissue (browning of white adipose tissue) or vice versa by differential gene expression, in response to thermogenic needs

Anatomic distribution

  • Subcutaneous fat: beneath the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin
  • Visceral fat: around internal organs
  • Yellow bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow
  • Intermuscular
  • Breast tissue
  • Distribution of brown adipose tissue: 
    • Fetus: prominent in the posterior cervical, axillary, suprailiac, and perirenal regions; also in the interscapular and deltoid regions 
    • Adults: persists around the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys, adrenals, aorta, mediastinum Mediastinum The mediastinum is the thoracic area between the 2 pleural cavities. The mediastinum contains vital structures of the circulatory, respiratory, digestive, and nervous systems including the heart and esophagus, and major thoracic vessels. Mediastinum and Great Vessels, and neck
Adipose tissue

Subcutaneous adipose tissue

Image: “Adipose Tissue” by Bruce Blaus. License: Public Domain, edited by Lecturio.

Development

Embryonic development

White adipose tissue: 

  • From 14 to 24 weeks of gestation: 
    • Adipocytes differentiate from perivascular undifferentiated mesenchymal cells or stem cells and progenitor cells and express peroxisome proliferator–activated receptor gamma/retinoid X receptor (PPARɣ/RXR) transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors.
    • Adipocytes that arise in subcutaneous sites are molecularly and functionally different from those that arise in visceral sites.
    • PPARɣ is considered the master regulator of adipogenesis.
  • Precursor lipoblasts accumulate small lipid vacuoles in their cytoplasm, which fuse to become larger typical unilocular adipocytes of white adipose tissue. 

Brown adipose tissue:

  • Arises from skeletal myogenic progenitor cells, with similar close relationship with angiogenesis, and express the transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors PR domain–containing 16 (PRDM16) and PPARɣ coactivator 1 (PGC-1)
  • Lipoblasts accumulate small lipid vacuoles, which remain separate to become typical multiloculated adipocytes of brown adipose tissue.

Postembryonic development

  • Growth in number and size of adipocytes continues through puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty.
  • New adipocytes may continue to form throughout the lifespan, especially if overnutrition (hyperalimentation) occurs.
  • Stem cells and preadipocytes can divide; mature adipose cells cannot.
  • Healthy versus unhealthy fat deposits:
    • Subcutaneous white adipose tissue, especially that in the gluteal–femoral region, is considered metabolically healthy.
    • Visceral white adipose tissue is associated with inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and increased risk of metabolic disease.

Gender differences

  • Begin in early childhood
  • Young girls have more adipose tissue than young boys
  • After puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty, the distribution and physiology differ.
  • Related to steroid hormone secretion

Females:

  • Estrogens and progesterone promote localization of more fat in the lower body.
    • Results in the gynecoid habitus of women (fat around hips, thighs, and buttocks)
    • These fat deposits are subcutaneous.
  • After menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause, women may store more fat around the waist and more visceral fat.
  • Women continue to accumulate fat relative to body weight throughout the teen years.
  • In premenopausal women, gluteal adipocytes are different because they: 
    • Undergo less lipolysis despite weight loss because cells have more catecholamine-sensitive α2 receptors, which inhibit lipolysis
    • Have higher lipoprotein lipase (LPL) levels, so they capture more circulating triglycerides
    • Are larger

Males:

  • Fat in the lower body is reduced by androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens, producing an android distribution of fat.
  • Store more abdominal (visceral) fat
  • More prone to “central” (visceral obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity)
  • Reach a peak in body fat content during early adolescence

Morphology and Histology

Morphology

White adipose tissue: 

  • Bright cadmium-like yellow, glistening, and greasy surface:
    • Yellow color imparted by carotenoids found in many vegetables and fruits 
    • Reflects the active metabolism of fat in white adipose tissue
  • Homogeneous diffuse appearance on cut section
  • Thin septae dividing poorly defined lobules
  • Thicker septae in areas of mechanical pressure (buttocks)
  • Variation in color indicates a pathologic process:
    • White or whitish yellow: fat necrosis
    • Pale yellow: lipoma Lipoma A lipoma is a benign neoplasm of fat cells (adipocytes) and the most common soft tissue tumor in adults. The etiology is unknown, but obesity is a predisposing factor; genetics also play a role, with multiple lipomas occurring in various inherited disorders. Lipoma
    • Reddish to orangish yellow: angiolipoma
    • Whitish yellow to white firmer nodules: liposarcoma

Brown adipose tissue: 

  • Reddish brown owing to abundant vascularity and numerous mitochondria within cells
  • Glandular lobulated appearance

Beige: lighter brown than brown adipose tissue

Microscopic appearance

White adipose tissue:  

  • A mature white fat cell is spherical; size: up to 120 μm in diameter (compare to RBC = 7 μm, lymphocyte = 12–16 μm, hepatocyte = 20–30 μm)
  • Cytoplasm: displaced and compressed to the perimeter by a single lipid vacuole; composed of 99% triglycerides
  • Nucleus:
    • Displaced peripherally by a lipid vacuole
    • Oval, thin, and small, with central minute clear vacuole
  • Adipocyte basement membrane: highlighted by reticulin and periodic acid–Schiff (PAS) stains 
  • Ill-defined lobules are separated by thin bands of collagen that are thicker in the buttocks.
  • Stroma: capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries (have intimate relationship with each adipocyte, similar to other endocrine organs), fibroblasts, macrophages, preadipocytes, stem cells
White adipose tissue

White adipose tissue: cells with flattened nuclei that are located peripherally

Image: “White adipose tissue” by OpenStax College, Anatomy and Physiology. OpenStax CNX. License: CC BY 4.0

Brown adipose tissue:

  • Organized into prominent lobules of cells
  • Lobules are divided by septa containing blood vessels and nerves.
  • Brown adipose tissue adipocytes: 
    • Multivacuolated and some univacuolated cells are present.
    • Size: 25–40 μm (size varies, depending on nutritional status)
    • Many large, round mitochondria (giving granular appearance to cytoplasm)
    • Nucleus: spherical, centrally located in the multilocular cells
Brown adipose tissue

Brown adipose tissue:
Brown adipose tissue contains multivacuolated adipocytes and has a characteristic brown color due to marked vascularization (4–5x more than white adipose tissue) and numerous mitochondria. The adipocytes are smaller than the ones in white adipose tissue and the nucleus is centrally located; white adipocytes are also scattered within normal brown adipose tissue.

Image: “Tecido adiposo multilocular brown adipose tissue” by Lucasmcorso. License: Public Domain

Beige fat: 

  • Intermediate microscopic appearance between white adipose tissue and brown adipose tissue
  • Varies depending on stage of induction

Physiology

Lipid storage

  • White adipose tissue is the largest and most efficient store of energy (as triglycerides).
  • LPL is synthesized by adipocytes and transferred to the adjacent endothelial cells.
  • LPL on the luminal surface of endothelial cells hydrolyzes triglycerides from chylomicrons (from the intestine) and very-low-density lipoproteins (from the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver).
  • Most of the released free fatty acids (FFAs) are taken up by the fat cells and re-esterified with glycerol phosphate within the adipocyte to form triacylglycerol.
  • Triacylglycerols are stored within the adipocyte’s lipid droplet.
  • Stored triacylglycerols are mobilized by lipase, which hydrolyzes stored triglycerides.
  • Mobilization of triacylglycerols is controlled by both neural and hormonal factors:
    • Norepinephrine:
      • Activates lipase
      • Denervated fat will continue to deposit even in a state of starvation.
    • Insulin: stimulates lipid synthesis and inhibits lipase
    • Glucagon and growth hormone: activate lipase 
    • Thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones
      • First increase lipogenesis
      • Then cause lipolysis
    • Cortisol’s effects depend on the physiologic context.
    • Androgens are anti-adipogenic and estrogens are pro-adipogenic.
  • The released FFAs may be re-esterified or released to the circulation and bound to albumin for transfer to other cells.

Endocrine function

Adipose tissue produces a number of hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and cytokines.

  • Leptin: 
    • Protein product of the ob gene
    • Acts on the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus to increase energy expenditure and decrease appetite 
  • Adiponectin:
    • Decreases gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis and stimulates glucose uptake
    • Modulates lipid catabolism
    • Obesity is associated with reduced levels of adiponectin.
  • Resistin:
    • Increases low-density lipoprotein (LDL) levels
    • Associated with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance
    • Proinflammatory effects
  • Aromatase: 
    • Converts androstenedione to estrone, the major source of estrogen in men and postmenopausal women
    • Expressed by the stromal cell fraction of adipose tissue and not the adipocytes
  • Interleukin-6 (IL-6): (30% of IL-6 is from adipocytes, stromal cells, and resident macrophages):
    • Stimulates hepatic triglyceride secretion and acute-phase reactants
    • Increases platelet number and activity
    • Increases expression of endothelial adhesion molecules
    • Release is induced by tumor necrosis factor Tumor necrosis factor Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF) α ( TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)-α) (implicated in anorexia of cancer).
  • Other cytokines: 
    • TNF TNF Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor Necrosis Factor (TNF)-α:
      • Expressed in preadipocytes
      • Blocks differentiation to mature adipocytes
    • Fibroblast growth factor 1: 
      • From microvascular endothelial cells in white adipose tissue
      • Stimulates preadipocyte differentiation and accumulation of triglycerides 
    • C3 and adipsin: proteins of the alternative complement pathway 
    • Plasminogen activator inhibitor 1 (PAI-1): 
      • Potent inhibitor of the fibrinolytic system (thromboemboli increased)
      • Insulin induces expression of PAI-1 by adipocytes.
      • Obesity is associated with elevated levels.

Heat production

  • Major function of brown adipose tissue: nonshivering thermogenesis; important for newborns
  • Brown adipose tissue is very vascular and regulated by sympathetic stimulation.
  • Many β1 and β2 adrenoreceptors regulate lipolysis and thermogenesis.
  • Brown adipose tissue has more and larger mitochondria than white adipose tissue, and these possess a unique decoupling protein called “thermogenin” (the protein product of the UCP-1 gene).
  • Thermogenin uncouples the oxidation of fatty acids from the generation of ATP.
  • The resultant energy is dissipated as heat.

Other functions of adipose tissue

  • Insulation from heat and cold by the subcutaneous layer 
  • Protective padding and structural support of visceral organs, mammary tissue, periorbital tissue, bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow, and in areas of mechanical stress (palms and soles of feet)

Clinical Relevance

  • Obesity: a disease of excessive fat accumulation by both hypertrophy and hyperplasia of white adipose tissue: “Overweight” is defined as a BMI (the weight in kilograms divided by the square of the height in meters) of 25–29.9 and “obese” as a BMI ≥ 30. In the United States, the prevalence of obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity is ~ 40%, and that rate is increasing. Obesity is usually due to a sedentary lifestyle and an increased caloric intake, but there are also uncommon secondary causes. Obesity is associated with a number of disabilities, including:
    • Hypertension, hypercholesterolemia, diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus type 2
    • Heart disease and dyslipidemia
    • Cancer
    • Osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis, gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout
    • Nonalcoholic fatty liver disease Nonalcoholic Fatty Liver Disease Nonalcoholic fatty liver disease is a spectrum of liver pathology that arises due to accumulation of triglycerides in hepatocytes. Risk factors include diabetes mellitus, insulin resistance, obesity, and hypertension, among others. Nonalcoholic fatty liver disease ranges from fatty liver or hepatic steatosis but can lead to nonalcoholic steatohepatitis (NASH), which features fatty deposits and inflammation. Nonalcoholic Fatty Liver Disease, gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract disease, GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease
    • Kidney disease
    • Sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep apnea, dementia, depression
    • Increased susceptibility to infections, including coronavirus Coronavirus Coronaviruses are a group of related viruses that contain positive-sense, single-stranded RNA. Coronavirus derives its name from "κορώνη korṓnē" in Greek, which translates as "crown," after the small club-shaped proteins visible as a ring around the viral envelope in electron micrographs. Coronavirus disease 2019 (COVID-19), influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza, and bacterial and fungal infections
    • Skin changes, including stretch marks (striae), acanthosis nigricans (likely due to sustained hyperinsulinemia), hirsutism in women
    • Metabolic syndrome diagnosed if 3 of the following 5 conditions are met:
      • Hypertension
      • Low levels of high-density lipoproteins
      • Abdominal obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
      • Increased triglyceride levels
      • Increased glucose levels
      • Mnemonic PHATS 3/5: Pressure up, HDL low, Abdominal obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, Triglycerides up, Sugars up
  • Cellulite: a cosmetic problem that refers to linear depressed streaks (mattress phenomenon) or dimpling in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin: Cellulite appears mostly on the thighs and buttocks, is more common in females, and results from an uneven dermal–hypodermal interface, with fibrous tissue surrounding the protruding adipous papillae. Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis is less common in men because they have a smoother, strand-free dermal interface in the thigh Thigh The thigh is the region of the lower limb found between the hip and the knee joint. There is a single bone in the thigh called the femur, which is surrounded by large muscles grouped into 3 fascial compartments. Thigh and buttock areas.
  • Lipodystrophies: rare congenital or acquired syndromes associated with a loss of healthy adipose tissue: Generalized lipodystrophy can be associated with diabetes, hepatic steatosis, pancreatitis, and metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome.
  • Fat necrosis: condition associated with mechanical trauma (e.g., fat necrosis of the breast Fat necrosis of the breast Fat necrosis of the breast is an inflammatory, benign condition resulting from injury to the breast tissue. Forms of injury include blunt traumatic injury as well as trauma from surgical procedures, biopsies, and radiation therapy. Fat Necrosis of the Breast), inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation (e.g., associated with acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis), or ischemia (e.g., omental infarction). 
  • Fat embolism: an embolus composed of a cluster of adipocytes that enters the bloodstream and results in the blockage of blood flow: Fat emboli can present as pulmonary emboli after fractures of the long bones owing to the release of bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow fat.
  • Calciphylaxis: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and subcutaneous fat necrosis, with small blood vessel necrosis, calcium precipitation, and thrombosis: Calciphylaxis is a complication of dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Overview and Types of Dialysis and renal failure and is also seen in primary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism This condition is often lethal.
  • Panniculitis: inflammatory infiltrates in the subcutaneous adipose tissue: There are many causes of panniculitis, including steroid withdrawal, diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis, pancreatic disease, α1-antitrypsin deficiency, and autoimmune diseases. Inflammation may involve eosinophils, neutrophils, granulomas, and histiocytes with lymphophagocytosis, among others. Panniculitis may sometimes resolve without treatment, but it is often managed with antibiotics and anti-inflammatory drugs.
  • Mesenteritis inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation (mesenteric panniculitis): usually benign condition presenting as space-occupying lesion consisting of chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation with fat necrosis and proliferation of myofibroblasts involving single or multiple areas of the mesentery: Mesenteritis inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation often presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, but it can also be asymptomatic. This condition mostly affects middle-aged males. Prognosis is excellent, with most lesions regressing within 2 years.
  • Tumors:
    • Hibernoma: a benign neoplasm of brown adipose tissue: Hibernoma is the only pathologic lesion of brown adipose tissue. Tumors mostly occur in sites corresponding to the distribution of brown adipose tissue—the interscapular area, neck, mediastinum Mediastinum The mediastinum is the thoracic area between the 2 pleural cavities. The mediastinum contains vital structures of the circulatory, respiratory, digestive, and nervous systems including the heart and esophagus, and major thoracic vessels. Mediastinum and Great Vessels, and axilla Axilla The axilla is a pyramid-shaped space located between the upper thorax and the arm. The axilla has a base, an apex, and 4 walls (anterior, medial, lateral, posterior). The base of the pyramid is made up of the axillary skin. The apex is the axillary inlet, located between the 1st rib, superior border of the scapula, and clavicle. Axilla and Brachial Plexus. Hibernoma presents as a painless slow-growing subcutaneous mass, and it may achieve a size of up to 23 cm. Treatment is surgical excision.
    • Lipoma: a benign neoplasm of adipocytes (white adipose tissue): Lipoma is the most common soft tissue tumor in adults. Many variants of lipoma Lipoma A lipoma is a benign neoplasm of fat cells (adipocytes) and the most common soft tissue tumor in adults. The etiology is unknown, but obesity is a predisposing factor; genetics also play a role, with multiple lipomas occurring in various inherited disorders. Lipoma exist, including angiolipoma, atypical lipoma Lipoma A lipoma is a benign neoplasm of fat cells (adipocytes) and the most common soft tissue tumor in adults. The etiology is unknown, but obesity is a predisposing factor; genetics also play a role, with multiple lipomas occurring in various inherited disorders. Lipoma, myxolipoma, and spindle cell lipoma Lipoma A lipoma is a benign neoplasm of fat cells (adipocytes) and the most common soft tissue tumor in adults. The etiology is unknown, but obesity is a predisposing factor; genetics also play a role, with multiple lipomas occurring in various inherited disorders. Lipoma. Lipoma usually presents as a painless soft tissue nodule. Diagnosis is usually established clinically and supported by tissue biopsy. The usual treatment is surgical excision, but smaller asymptomatic lesions may not require any treatment.
    • Liposarcoma: a rare malignant tumor originating from adipocytes. This tumor is a kind of soft tissue sarcoma. Symptoms depend on the site of origin. Clinically, liposarcoma may be difficult to distinguish from a lipoma Lipoma A lipoma is a benign neoplasm of fat cells (adipocytes) and the most common soft tissue tumor in adults. The etiology is unknown, but obesity is a predisposing factor; genetics also play a role, with multiple lipomas occurring in various inherited disorders. Lipoma. Diagnosis is established with biopsy, and the mainstay of treatment is complete surgical excision.

References

  1. Brooks, J. S. J. (2020). Adipose Tissue. In Mills, S. E. (Ed.), Histology for Pathologists (5th ed., Chap. 6). 
  2. Harvey, I., Boudreau, A., Stephens, J. M. Adipose tissue in health and disease. Open Biology, 10(12), 200291. https://doi.org/10.1098/rsob.200291
  3. Pawlina, W., Ross, M.H. (2020). Adipose Tissue. In Histology: A Text and Atlas with Correlated Cell and Molecular Biology (8th ed., Chap. 9)
  4. Akalestou, E., Genser, L., Rutter, G. A. (2020). Glucocorticoid Metabolism in Obesity and Following Weight Loss. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.00059
  5. Stimson, R. H., Anderson, A. J., Ramage, L. E., et al. (2017). Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct. Diabetes, Obesity and Metabolism, 19(6), 883–891. https://doi.org/https://doi.org/10.1111/dom.12899
  6. Toward a consensus view of mammalian adipocyte stem and progenitor cell heterogeneity. (2020). Trends in Cell Biology, 30(12), 937–950. https://doi.org/10.1016/j.tcb.2020.09.\
  7. Perreault, L., Laferrère, B. (2020). Overweight and obesity in adults: Health consequences. UpToDate. Retrieved January 23, 2021, from https://www.uptodate.com/contents/overweight-and-obesity-in-adults-health-consequences
  8. Divoux, A., Moutel, S., Poitou, C., Lacasa, D., Veyrie, N., Aissat, A., Arock, M., Guerre-Millo, M., Clément, K. (2012). Mast cells in human adipose tissue: Link with morbid obesity, inflammatory status, and diabetes. Journal of Clinical Endocrinology and Metabolism, 97(9), E1677–E1685. https://doi.org/10.1210/jc.2012-1532

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