Adipose tissue

Adipose tissue is a type of connective tissue that is composed mainly of adipocytes. It is found throughout the body and fulfills a number of important functions: it provides structural support and protective padding for major organs (e.g., kidneys), it serves as an insulating layer that prevents cutaneous heat loss, and it stores energy for longer periods of fasting. While the insulating and energy storage functions of adipose tissue provide decisive evolutionary advantages, their roles have diminished in modern times. Today, humans also rely on clothing for insulation and, in industrialized societies where food is readily available and affordable, its positive role as an energy reservoir has reversed to become a major health concern (obesity). However, in infants, adipose tissue continues to play a central role in the maintenance of body heat, and in individuals with severe illness, energy stores within the body make an essential contribution to sustaining the body.

There are two types of adipose tissue. Brown adipose tissue is abundant in neonates but recedes in adulthood. Its primary function is to prevent hypothermia through thermogenesis. White adipose tissue remains present throughout a lifetime and serves as the body's most important energy reservoir and also produces hormones.

Structure

• Macroscopic
  • Divided into lobules by connective tissue septae that also house nerves, vessels, and lymphatics.
  • Color: yellow
• Microscopic
  • Composed of monovacuolar adipocytes with a flattened nucleus located at the periphery
    • Vacuoles are filled with triglycerides.
    • Color: white
    • Immunohistochemistry: stains positive for vimentin
  • Surrounded by vascularized connective tissue

Function

• Energy storage: energy reservoir (triglycerides)
  • Starvation → triglyceride breakdown from adipose tissue → ketone bodies → primary source of energy for the brain
  • Triglyceride breakdown prevents degradation of protein and organ failure
• Regulation
  • An anabolic state of metabolism results in increased lipogenesis through both hypertrophy (lipid vacuole expands) and hyperplasia (via stem cell reserves) of adipocytes.
  • A catabolic state of metabolism results in lipolysis.
• Insulation: subcutaneous tissue provides thermal insulation
• Structural support
  • Padding in areas exposed to mechanical stress (foot sole)
  • Holds organs in place (e.g., keeping eyeball in orbit, renal pelvis in renal sinus)
• Hormone (adipokine) secretion
  • Leptin
    • Takes effect at the ventromedial hypothalamic nucleus and induces a feeling of satiety (appetite suppressant).
    • Decreased in individuals with lack of sleep or during times of starvation
    • Mutations in the leptin gene → congenital obesity
    • Increased during states of inflammation
  • Estrogens: adipocytes express cytochrome P-450 aromatase, which catalyzes the conversion of steroids to estrogens (i.e., it converts androstenedione to estrone).
    • Obesity → increased adipose tissue → increased conversion of androgen to estrogen → increased exposure to estrogens → increased risk of breast and endometrial cancer.
• Reservoir for lipophilic biomolecules (e.g., fat-soluble vitamins)
• Insulin effects on adipose tissue
  • ↑ Glucose intake for lipogenesis
  • ↓ Lipolysis
  • Expression of GLUT4 transporters → increased glucose intake into adipocytes.

Individuals with congenital leptin deficiency (e.g., due to leptin gene mutations) present with constant hunger, hyperphagia, and severe obesity beginning in the first few months of life.

Blocking aromatase activity is the mechanism of treatment of estrogen-dependent diseases such as breast cancer, endometriosis, and endometrial cancer. Obese women are more prone to develop these conditions due to higher circulating levels of estrogens synthesized by their adipose tissue.

Occurrence

• Depot fat: subcutaneous tissue, abdominal region
• Insulation fat: subcutaneous tissue
• Structural fat
  • Macroscopically visible: orbits, coronary sulcus of coronary arteries, adipose capsule of the kidney, foot sole, greater omentum
  • Microscopically visible: Small adipocyte groups occur everywhere in the body's stroma.

Development

Mesoderm germ layer → mesenchymal stem cells → preadipocytes (mitotically active) → adipocytes (ripe, mitotically inactive)

A persistently high-calorie intake that exceeds daily needs can lead to a pathological increase of white adipose tissue, causing obesity.

Structure

• Macroscopic
  • Color: brown due to high iron-containing mitochondrial content
  • Same structure as white adipose tissue
• Microscopic
  • Rich in mitochondria and capillaries (see “Function” below)
  • Smaller than adipocytes of white adipose tissue
  • Contain multiple vacuoles (instead of only one as seen in white adipose tissue)

Function

Nonshivering thermogenesis (heat production)

• Mechanism: uncoupling of the respiratory chain in mitochondria with the help of thermogenin to generate heat instead of ATP
• Procedure: cold stimulus → increased activity of sympathetic nervous system → release of norepinephrine → stimulation of β₃-adrenergic receptors of adipocytes for fat burning (beta oxidation)
  • In beta oxidation, many reducing equivalents (NADH + H⁺, FADH₂) accumulate and are introduced into the respiratory chain
  • The uncoupling agent thermogenin, a protein channel, is incorporated into the inner mitochondrial membrane → increased permeability of mitochondrial membrane → influx of H⁺ into the matrix of the mitochondrion, bypassing the ATP synthase channel → electron transfer continues but ATP synthesis stops → the energy from the proton motive force is released in form of heat instead of producing ATP from ADP
• Importance: heat production of the newborn and hibernating animals.

Occurrence

• Infants: especially in the neck and thorax
• Adults: only surrounding the vertebra, vessels (along large arteries), mediastinum, and clavicle

Development

• Embryonic: mesoderm germ layer → mesenchymal stem cells → brown adipose tissue
• In adult organism: regression over the course of a lifetime

• Lipoma
• Liposarcoma
• Fat necrosis
• Fat embolism
• Cholesterol stones
• Overview of nutrition
• Fat-soluble vitamins
• Obesity
• Estrogen and associated diseases
• Fatty casts
• Fatty stool
• Fatty liver
• Statins