Histology Chapter 6 Adipose Tissue

Development from White & Brown Fat

*With adaptation to cold temperatures beige adipocytes change reversibly, forming many more small lipid droplets, adopting a gene expression profile more like that of brown fat, and begin to release heat (see below).

White Adipose Tissue

*unilocular* single large droplets of triglycerides

leptin

- 16-kDa polypeptide hormone - a "satiety factor" with target cells in the hypothalamus, other brain regions, and peripheral organs - helps regulate the appetite under normal conditions and participates in regulating the formation of new adipose tissue

White adipocytes - three sources of stored triglycerides

■ Dietary fats brought to the cells via the circulation as chylomicrons, ■ Lipids synthesized in the liver and transported in blood with very-low-density lipoproteins (VLDLs), ■ Free fatty acids and glycerol synthesized by the adipocytes.

uncoupling protein-1 (UCP1) or thermogenin

- Heat production in brown adipocytes is greater than that of other cells because their inner mitochondrial membranes have greatly unregulated levels of the transmembrane protein *uncoupling protein-1 (UCP1) or thermogenin*. - In the presence of free fatty acids, UCP1 permits the *flow of protons from the intermembranous space to the matrix* *without* passing through ATP synthetase complexes. - Instead of producing ATP, the energy associated with this proton flow dissipates as heat.

Proliferation of Progenitor Cells

- Humans are born with stores of white adipose tissue, which begin to accumulate by the 14th week of gestation - visceral and subcutaneous fat is well-developed before birth - Proliferation of progenitor cells diminishes by late gestation, and adipose tissue increases mainly by the filling of existing adipocytes until around age 10, followed by a period of new fat cell differentiation which lasts through adolescence. - New adipocyte formation occurs around small blood vessels, where undifferentiated mesenchymal cells are most abundant.

VLDLs

- Smaller than chylomicrons - greater surface-to-volume ratio), of similar lipid and protein composition to chylomicrons - synthesized from lipids in *liver cells* - Levels of circulating lipoproteins according to density, from VLDL to high-density lipoprotein (HDL)are routinely measured in clinical tests for blood lipids, after fasting to allow depletion of chylomicrons

lipomas

- benign tumor generated by unilocular adipocytes, relatively common - *liposarcomas*malignant adipose tumors occur infrequently - *hibernomas* - Fetal lipomas of brown fat

Brown Adipose Tissue

- constitutes 2%-5% of the newborn body weight, located mainly in the back, neck, and shoulders, but it is greatly reduced during childhood and adolescence. - In adults it is found only in scattered areas, especially around the kidneys, adrenal glands, aorta, and mediastinum. - The color of brown fat is due to both the very *abundant mitochondria* (containing cytochrome pigment) scattered among the lipid droplets of the fat cells and the *large number of blood capillaries* in this tissue - Brown adipocytes contain many small lipid inclusions and are therefore called *multilocular* - The small lipid droplets, abundant mitochondria, and rich vasculature all help mediate this tissue's principal function of *heat production* and warming the blood.

Brown Adipose Tissue Development

- develops from mesenchyme, but involves preadipocytes in a different embryonic location (paraxial) - emerge earlier than white fat during fetal development - maximal relative to body weight at birth and partially disappears by involution and apoptosis during childhood - amount and activity of brown fat are higher in lean individuals. - number of brown adipocytes increases during cold adaptation, usually appearing as clusters of multilocular cells in white adipose tissue - beige cells or preexisting progenitor cells

nonshivering thermogenesis

- main function of multilocular adipose cells - Heat Production: nerve impulses liberate norepinephrine - multilocular adipocytes quickly metabolized their fatty acids of - consequent increase in O2 consumption and heat production. -Warms the tissue and locally circulating blood, which then distributes the heat throughout the body.

obesity

- nutritional intake exceeds energy expenditure - Although adipocytes can differentiate from mesenchymal stem cells throughout life, adult-onset obesity mainly involves increasing the size of existing adipocytes (hypertrophy). - Childhood obesity, in contrast, often involves increases in both adipocyte size and numbers due to the differentiation of more preadipocytes from mesenchymal cells (hyperplasia). - Weight loss after dietary changes is due to reductions in adipocyte volume, but not their overall number.

Chylomicrons

- particles of variable size - formed from ingested lipids in epithelial cells lining the small intestine and transported in the blood and lymph. - core containing mainly triglycerides, surrounded by a stabilizing monolayer of phospholipids, cholesterol, and several apolipoproteins

Brown Adipose Tissue Structure

- polygonal - generally smaller than white adipocytes - more centrally located nucleus - often closely packed around large capillaries - subdivided by connective tissue partitions into lobules that are better delineated than the lobules of white adipose tissue. - Cells of this tissue receive direct sympathetic innervation, which regulates their metabolic activity.

adipocytes/adipose tissue

- typically found isolated or in small groups within loose or dense irregular connective tissue but occur in large aggregates in adipose tissue or "fat" in many organs/ body regions. - represents 15%-20% of the body weight in men, somewhat more in women. - serve as storage depots for neutral fats, chiefly triglycerides (long-chain fatty acyl esters of glycerol) specialize in concentrating triglycerides as lipid droplet(s) (other cells normally accumulating relatively little lipid) - function as key regulators of the body's overall energy metabolism - active cells metabolically, responding to both nervous and hormonal stimuli - endocrine organ: release hormones and various other important substances as the "center of nutritional homeostasis" - conducts heat poorly - provides thermal insulation for the body. - fills spaces between other tissues, helping to keep some organs in place. - Subcutaneously shape the body surface, and cushion regions subject to repeated mechanical stress such as the palms, heels, and toe pads.

Other components of adipose tissue

- white fat is subdivided into incomplete lobules by partitions of connective tissue containing a vascular bed and nerve network. - Fibroblasts, macrophages, and other cells typically comprise about half the total cell number in white adipose tissue. - Reticular fibers form a fine interwoven network that supports individual fat cells and binds them together, and the microvasculature between adipocytes may not always be apparent in tissue sections.

lipoprotein lipase

-synthesized by the adipocytes and transferred to the capillary cell membrane - chylomicrons and VLDLs are hydrolyzed at the *luminal surfaces of blood capillaries* by this enzyme - Allows free fatty acids to then enter the adipocytes by both active transport and diffusion.

Why are triglyceride lipids the preferred form of nutrient storage?

1. Insoluble in water: lipids can be concentrated with no adverse osmotic effects on cells. 2. The caloric density of triglycerides (9.3 kcal/g) is twice that of proteins or carbohydrates, including glycogen, making these simple lipids the most efficient

two major types of adipose tissue

1. White adipose tissue, the more common type specialized for fat storage, consists of cells each containing one large cytoplasmic droplet of whitish-yellow fat. 2. Brown adipose tissue contains cells with multiple lipid droplets interspersed among abundant mitochondria, which helps give this tissue a darker appearance - release heat and function to warm the blood. **Both types have a rich blood supply and the adipocytes, unlike other cells of connective tissue proper, are individually surrounded by a thin external lamina containing type IV collagen.