Adipose Tissue Growth and Development (ANSC)

1. Visceral (2)

(messenteric/perirenal PR) Earliest depot to form appreciable quantities (located within the body cavity) and then mesenteric is earliest of visceral depots

How can fat affect growth? (4)

**Drag on growth because of inflammatory response** 1. Secretes molecules regulating vasculature 2. Secretes molecules regulating innate immune system 3. Secretes molecules regulating energy homeostasis 4. Extracellular matrix components (type 6 collagen)

"TAKE HOME MESSAGE" Adipose tissue is important in growth and development because: (3)

**It can affect GROWTH EFFICIENCY and CARCASS VALUE in several ways** 1. Adipocyte size - balance between lipid filling and lipid mobilization 2. Immune/endocrine function and how they effect feed intake and muscle metabolism -secretions can modulate growth

PPAR"gamma" (4)

**Master switch of adipogenesis** 1. Its expression helps C/EBP"beta" induce C/EBP"alpha" which in turn helps maintain PPAR after C/EBP"beta" expression dwindles 2. PPAR"gamma" drives the expression of a host of adipocyte-specific genes that allow the cell to store and release fatty acids 3. PPAR"gamma" is also anti-mitotic and is the major reason terminally differentiated adipocytes are unable to re-enter the cell cycle

3. Secretes molecules regulating energy homeostasis (3)

*Leptin* 1. Can boss liver and metabolism 2. Can change how tissues function and respond

Structure (3)

1. "Lobules" of fat separated and supported by loose C.T. called "septa" 2. Septa carries blood vessels and nerves to adipose tissue ("food supply" and regulation) 3. C.T. within fat cells brings fat cells in contact with capillaries

3. Intermuscular fat (I.M.) (3)

1. "seam fat"/ fat located around and between individual muscles or groups of muscles 2. represents the 3rd fat depot to develop 3. Species like cattle and sheep - seam fat may contribute substantially to the total fat content of the body

Stimulation of innate pathway can change growth and development (4)

1. ? 2. Liver delivers lipid like things 3. Saturated fats turn ON inflammation; unsaturated fats turn OFF inflammation 4.Proinflammatory cytokines can stunt growth

Reasons BAT shouldn't be ignored (2)

1. Accumulating evidence suggests that adults retain metabolically active BAT 2. The manipulation of fat stores - promotion of increased BAT development offers the possibility of increasing energy expenditure without necessarily causing dysfunction in other tissues.

Adipocyte Lineage (2)

1. Adipose tissue hyperplasia (fat cell #) is the process of proliferation, differentiation, and maturation of stem-like cells of mesodermal origin to form cells of the fat cell lineage capable of conducting lipid metabolism 2. No I.D. of precursor to adipocytes

Adipose Tissue Metabolism (3)

1. Adipose tissue is very metabolically active 2. Overall lipid accumulation is determined by the balance between: ~a. Lipid Storage (de novo synthesis by lipogenesis or through absorption of preformed FFA from blood) ~b. Lipid Metabolism (lipolysis-breakdown of triglyceride to free fatty acids and glycerol 3. REMEMBER: hyperplasia sets the potential for adipose tissue mass while hypertrophy determines the extend to which this potential is reached.

Functions of WAT: ENDOCRINE FUNCTION (3)

1. Adipose tissue secretes signal molecules locally and into the blood -act locally as pro inflammatory cytokines 2. These factors come from both fat cells (preadipocytes and adipocytes) and macrophages that reside in WAT 3. Paracrine, autocrine, and endocrine -local environment may have increased effect that might not be detected in blood

Functions of WAT: Innate Immunity and Inflammation (4)

1. Antigen-nonspecific, "1st line of defense" - functions in nonmemory immune response 2. Cells innate immune function can react to molecules that "slough" off of pathogens just like these foreign molecules were endogenous hormones 3. This triggers responding cell to release pro-inflammatory cytokines - triggers an acute phase and finally an adaptive (antibody-mediated) response 4. In adipose, preadipocytes, adipocyte, and macrophages can participate in this pathway

Nutrients can act as hormones: (2)

1. Can act directly on the brain/neurons -glucose can bind to neuron and boss it (so can fatty acids, leptin, etc 2. NPY causes hunger -leptin turns NPY off -change in NPY is sensed by GnRH (should flip it on)

CURRENT model for fat development: (3)

1. During the final 3rd of gestation, mesenchymal cells migrate and form "nodes" 2. Blood vessels then form in the enter of the aggregates and adipocytes form on the outside of the blood vessels 3. Adipocytes then secrete angiogenic factors (development of blood vessels) that stimulate further blood vessel formation -leads to more adipocyte recruitment etc and "fat lobules" develop forming the foundation of the depot

Postnatal growth curve (2)

1. Efficient production of meat animals with maximum muscle and minimum fat is major goal of the meat industry given consumer demand for lean meat 2. Excess fat associated with meat is generally considered undesirable and is therefore regarded as waste Graph on pg 19 - arrow shows approximate point where carcass would have approximately 30% fat

Endocrine system (3)

1. Endocrine system: system of small organs that involve the release of extracellular signaling molecules called hormones 2. endocrine system is information signal system that mainly uses blood vessels as information channels 3. glands located in many regions of the body release hormones into bloodstream

C/EBP beta (2)

1. Expressed early in the conversion of adipoblasts to preadipocytes and are down regulated as terminal differentiation progresses 2. Role is to 1st enable preadipocytes to reenter the cell cycle to facilitate "clonal expansion" and then to induce PPAR"gamma" and C/EBP"alpha"

Adipose and developmental trajectory (4)

1. Fat can be a drag on production efficiency bc its expensive to make 2. Fat can stunt growth because of the things it secretes (pro-inflammatory cytokines) -Ex: GH/insulin bosses tissue (make more protein) but fat cell is nailing these tissues with cytokines - cause production of less protein 3. Signal cell to do the opposite of build and grow because you are "sick" (i.e. your energy is needed somewhere else) - animal might not even be sick, just fat cells acting weird 4. Just because fat cells participate in inflammatory pathways, doesn't mean they are important for fighting sickness - may be result of management/production process for the animals (how rations effect muscle/fat development)

Post natal growth: adipose tissue normally appears in discreet anatomical locations termed "depots" (3)

1. Fat located within meat imparts a desirable flavor to some meat products - increasing their value 2. Fat deposition in growing animals becomes a liability to producers when it adds to production costs and consumer rejection (trim fat) 3. Adipose tissue development is important due to the effects of fat on meat quality and production efficiency - both desirable and undesirable depots

What is the growth problem ("challenge")? (3)

1. Feed is the primary cost to the producer when growing meat animals in concentrated/confinement systems 2. Traditionally the industry has responded by emphasizing rapid growth ~ Selection programs/improved nutrition ~Metabolic modifiers that increase feed efficiency and lean tissue deposition while limiting fat accretion 3. Meat quality often adversely influenced by increased FE and lean tissue accretion ~Increased lean results in decreased intramuscular fat (marbling)

Adipose tissue function (2)

1. Functions as an energy reservoir 2. Functions as an endocrine organ that secretes a multitude of factors that can effect feeding behavior and metabolism

Primary Role of BAT (2) (2)

1. GENERATE HEAT 2. Expresses uncoupling protein 1 (UCP-1) which "uncouples" oxidative phosphorylation - recycles protons back to mitochondria rather than allowing them down the proton gradient where they would make ATP -- trying to block ATP synthesis

Nuclear Transcription Factor Classes (2)

1. HORMONE ACTIVATED TFS: ~ CAAT-Enhancer Binding Proteins (CEBP"alpha", CEBP"beta") ~ Basic Leucine zipper DNA binding domain 2. LIGAND-ACTIVATED NUCLEAR RECEPTORS: (zinc finger DBD) a. Peroxisome, Proliferator-Activated Receptors (PPAR"alpha", PPAR"gamma") b. Retinoic Acid Receptors (RXRs, RARs) c. Orphan Receptors (ex. COUP-TF)

Hormones (2)

1. Hormones regulate many functions of an organism (growth and development, tissue function, and metabolism, as well as sending messages and acting on them 2. Adipose tissue releases hormones into the blood so adipose can be thought of as an "endocrine gland"

BAT may be factor affecting feed efficiency (2)

1. It generates heat which is a DRAG on feed efficiency because it wastes energy 2. Feed is converted to heat instead of muscle or fat

Pro-inflammatory cytokines (4)

1. Locally acting - by autocrine and paracrine methods 2. will be CATABOLIC - tell tissues to break stuff down -break down proteins, release amino acids -break fats down/triglycerides, release free fatty acids 3. can completely change the way muscles work -tells muscles to breakdown protein 4. change metabolism of a tissue -initiate inflammatory response/tricks body into thinking it is sick -redirects energy to immune cells

Model for depot development: (3)

1. Mesenchyme is a type of loose C.T., of mesodermal origin and located within the embryonic mesoderm 2. Consists of a ground substance matrix containing a loose aggregate of unspecialized cells which are capable of developing into C.T., bone, cartilage, the lymphatic system, and the circulatory system 3. Origin of fat pad primordial not known - thought that primitive pluripotent mesenchymal cells aggregate to form a "primordial" and clusters of differentiation are determined by cell-cell or cell-environment interactions

BAT (3)

1. Multilocular lipid storing cells - more capillaries than WAT because of higher oxygen demand - lots of O2 delivered, lots of blood, lots of hemoglobin 2. Found in discrete depots 3. "Convertible" after B-adrenergic stimulation

PPAR activation (2)

1. Nuclear receptors activated by fatty acids and lipid derivatives 2. Also activated by several classes of synthetic molecules -Thiazolidinediones -Fibrates -NS anti-inflammatory drugs

PPARs (Peroxisome Proliferator-Activated Receptors (3)

1. Nuclear receptors, active as heterodimers with RXR 2. 3 different isotypes (alpha, beta/delta, and gamma) 3. Mainly involved in the control of lipid metabolism

paracrine and autocrine action (2)

1. Secretion can interfere with normal development, regulation, and growth 2. Effect production efficiency

Functions of WAT: LIPID METABOLISM (5)

1. Synthesis, storage and release of fatty acids by fat cells (adipocytes) -Energy density of lipids is greater than that of carbohydrates and proteins (6-8x more energy dense than protein) -external signs control whether lipid filling or lipid mobilization occurs 2. Protection of vital organs 3. Physical support and insulation

Regulation of Adipogenesis: (3)

1. Temporal pattern of transcription factor expression (mouse models) is not observed during the differentiation of primary pig preadipocytes 2. S-V cells from newborn pig adipose tissue are probably more advanced in development than preadipocytes in the 3T3-L1 cell model 3. S-V cells may be in a state where PPAR"gamma" and C/EBP"alpha" are expressed but new signals or vascularization are needed before cells are fully committed and lipid filling begins

Fat is laid down in 4 major depots in beef, lamb and pork

1. Visceral 2. Subcutaneous fat 3. Intermuscular fat (I.M.) 4. Intramuscular fat (I.F. or "marbling"

Anatomical Location Summary (in order of development) ~(4) (species differences)

1. Visceral ~Perinephric: fat surrounding kidneys, pelvis, and heart (KPH ~ Omental/Mesenteric: fat surrounding the GI tract 2. Subcutaneous: external fat under hide (largest % fat contribution) 3. Intermuscular: fat between muscles 4. Intramuscular: fat within muscle (marbling) - specifically with perimysium

Two types of fat tissue:

1. White adipose tissue (WAT) 2. Brown adipose tissue (BAT) - extensive vascularity gives it dark color

C/EBP"alpha" (2)

1. Works in concert with PPAR to drive expression of adipocyte-specific genes specifically those conferring insulin sensitivity on the cell 2. Also maintains robust expression of PPAR"gamma"

Cell types in adipose tissue (7)

1. adipocytes 2. adipoblasts 3. fibroblast 4. macrophages 5. endothelial cells of blood vessels 6. pericytes (may g.r.t. adipocytes - source of stem cells) 7. mast cells: release heparin and histamine

WAT (4)

1. development continues throughout life 2. well vascularized with each adipocyte being in contact with a single capillary 3. secretion of various peptide and non-peptide molecules 4. Less innervated than BAT but does have sympathetic innervation

4. Intramuscular fat (I.F. or "marbling") (3)

1. last fat depot to develop and consequently contributes the least to total carcass fat 2. this depot represents fat deposited within a muscle 3. Marbling is related to eating quality of meat because it is highly correlated to the flavor of intact meat products (steaks/chops especially)

2. Secretes molecules regulating innate immune system (2)

1. poor aspect of endocrine function - not beneficial to animals -more prone to cancers, diseases, etc because of unnecessary/improper inflammatory response 2. Pro-inflammatory cytokines released and trick body into thinking it is sick and change metabolism

What is adipose tissue? (4)

1. specialized loose C.T. with many lipid-filled adipocytes (store fat) 2. network of C.T. fibers 3. variety of other cell types, blood vessels, lymph nodes 4. all held in matrix of collagen fibers

Leptin and the endocrine function of fat (3)

1. stimulates lipolysis - bosses metabolic function to make fat smaller 2.inhibits lipogenesis 3. Impairs insulin signaling - insulin tells fat to store glucose as a lipid but leptin screams no

2. Subcutaneous fat (3)

2nd fat depot to be detectable; located just under the skin back fat 1. Outer layer (O.S.) - 1st to develop and is the oldest SQ fat layer at any age ~ thought to act as insulation 2. Middle layer (M.S.) - 2nd layer to form - normally the thickest layer postnatally representing the bulk of SQ fat in all species *most metabolically active layer* 3. Inner Layer (I.S.) - latest developing layer - very small/thin - sometimes very difficult to detect in lean carcasses

SREBP-1 (2)

Basic helix loop helix DBD 1. Plays a major role in the delivery of endogenous ligands to PPAR"gamma" thus contributing to maximal activity of the master switch

Contribution to fat cell # (1)

Much fat cell hyperplasia takes place prenatally but recruitment of new fat cells can occur perinatally as well

What kind of fats can make tissues inflamed? (1)

Saturated fats

1. Secretes molecules regulating vasculature (1)

Vascular endothelial growth factor - builds vasculature to support fat growth