Exam 1 Flashcards
Hypertrophy in muscles
- increase in postnatal muscle mass
- satellite cells
- Growth of muscle reflects in its mass
- > the number of cells present and the amount of protein accumulated in each cell
Altering Muscle Hyperplasia
- MYOSTATIN is the key player
- Negative regulator of muscle growth
- Reduce or knock out myostatin to increase muscle fiber hyperplasia
Ex. Mighty mouse, Piedmontese, Belgian Blue - myomiRNA, muscle specific miRNA, negative regulators of gene expression; however some also activate gene expression
Ex. Texel sheep
Extracellular Matrix Proteins (ECM) Role in Control of Cartilage Maturation(Growth Plate)
- ECM is critical for proper differentiation and organization of growth plate chondrocytes
- Mutations in collagen XI causes severe skeletal abnormalities
- Deficiency of collage XI causes death at birth
Muscle Pathologies (Dystrophies)
- rapid loss of muscle protein and skeletal muscle mass with muscular dystrophies
- due to greatly increased protein degradation with little or no change in muscle protein synthesis
What type of animal should we farm more of?
- ruminants, like cattle, because they can take grass and things we can not utilize in our diets and make it into consumable produce
PAX 7 Role in Myogenesis
- Works with PAX3 in early development
- predominates during post-natal growth and muscle regeneration in the adult
- Satellite cells
Intramuscular (IM or marbling) Adipose Depot
- fat deposited within the muscle
- primary factor determining quality grade in young beef carcasses (impacts value)
- some consumers willing to pay for high marbling
- increase marbling score=increase number and area occupied by fat cell
- accumulate in close proximity to blood vessels
- extended time-on-feed increases excess fat deposition
- postnatal adipose tissue dev was believed to occur in order of internal, intermuscular, subcutaneous and intramuscular, BUT new research shows its simultaneous
Callipyge Gene (CLPG) Sheep Mutation
- Specific muscle hypertrophy, only certain muscles affected
- unique inheritance pattern
- natural mutation that increases muscle mass
- Hypertrophy of loin and leg, “beautiful buttocks”
- Evident at 4-6 wk of age
- Non-mendelian Genetics
- Polar overdominance
- Heterozygotes who inherit the CLPG mutation from sire(paternal/dad) express the phenotype
- Homozygotes are normal in appearance
- leg grows at a faster rate than the loin
Fetal phase in embryonic development
- maturation and specialization of tissues
- dramatic increase in size of existing organs and tissues
- over 75% of fetal growth occurs in this phase
- becomes recognizable as to what species animal is
2 Types of bone
1) Hard, Compact or Cortical
- Dense, hard nature
- Cortical ring surrounding a bone marrow cavity of long bones
- 80% of bone in the skeleton
2) Spongy
- Sponge-like appearance
- vertebrae, flat bones or end of long bone
- Deposited in a fibrous network
- Found in axial skeleton (vertebrae) as well as in epiphyseal and marrow regions of long bones
- 20% of bone in skeleton
Growth
- general and normal expansion of size as produced by the accretion of tissues similar in composition to that of original tissue or organ
- if an animal has increased in weight, it has grown
- cannot use weight to determine growth in finishing lots because the animals have put on excess fat
Lipolysis
- release of fatty acids from triglycerides
- hormone controlled process
Advantage of brown fat in sheep
- increasing brown fat can help to increase survival rate of lambs after birth
- maternal supplementation with Arginine can increase BAT in lambs
- must supplement to ewe bc they do not have brown fat
Maturation in Myogenesis
- functional muscle fibers form from myotubes
- once myoblasts fuse into myotubes, they further differentiate to mature
Regulatory factors
- factors that regulate determination or differentiation
Ex: muscle regulatory factors - specific factors to regulate the process
Order of adipose deposition
- Perirenal
- Visceral
- Intermuscular
- Subcutaneous
- Intramuscular
What happens as muscle grows?
- increase in DNA
- Increase in protein
- Increase in the amount of protein per unit of DNA
M line in a sarcomere
- center of thick filament
Two Osteogenic pathways in Osteogenesis
1) intramembranous ossification
- flat bones of the face, most of the cranial bones, and the clavicles (collarbones)
2) endochondral ossification
- long bones
Sarcomere
- smallest unit of contraction
- many of them
- one z line to z line makes up a single sarcomere
- length of sarcomere influences meat tenderness
- > if in contracted state meat will be tougher and vice versa
Visceral(VS) Adipose Depot
- located within the body cavity in close association with the viscera
Myofibrillogenesis (part of differentiation)
- development and formation of myofibrils(muscle fibers)
- 1st myofibrils are unstriated
- as myogenesis proceeds, those immediately beneath the sarcolemma are the first to become striated
- nuclei migrate from their central core position to the periphery
- Increase in number by further fusion of myoblasts
Calcium metabolism
- is a complex system
- Ca++ very tightly regulated
- Will be released into the bone from the blood stream
1) Low blood Ca - Release of PTH which stimulates osteoclast activity and corresponding resorption of bone calcium
2) High blood Ca - Thyroid gland releases Calcitonin
- Stimulates osteoblast activity with a corresponding deposition of calcium into bone
Sliding Filament Theory
- muscle shortens during contraction without either filament (thick or thin) changing in length
- instead filaments slide past eachother in their region of overlap
- force of contraction is generated by the process that actively moves thick and thin filaments past eachother
SNP(single nucleotide polymorphism) Within the Myostatin Gene
- SNPs transition the G allele to an A allele in the 3’ UTR
- Creates a target site for miRNAs
- miRNA down-regulates myostatin, causes hyperplasia
Adipose tissue role
- stores triglycerides and acts as an energy reservoir
- store surplus lipid energy for subsequent mobilization in times of need
- protection for vital organs (KPH)
- reservoir for fat storage (lipids)
miRNA
- Small non-coding RNA which post-transcriptionally regulate gene expression
- most are negative regulators of gene expression
- if binds to mRNA during translation mRNA is degraded and the protein is not produced
How is growth accomplished?
- Hyperplasia
2. Hypertrophy
Double Muscling- the cause and effect
CAUSE - Loss of active myostatin - Myostatin is a NEGATIVE regulator of muscle growth - little amount of myostatin means that animal will develop extra muscle fibers and have increased hyperplasia (lots of muscle development) EFFECT - Increased hyperplasia - Born with double the number of muscle fibers - improved sensory traits - increases the percentage of carcass weight as primal cuts in finished steers - muscle fiber diameter does not differ only number
Nebulin
- myofibrillar protein
- parallels thin filament to Z line
Serial Slaughter Studies
- uniform group of steers managed the same way
- slaughter them at given intervals of time across a finishing period
How can DNA and protein increase?
- Satellite cells
- > First identified in 1961 by Alexander Mauro
- > It is a postnatal source of DNA
- > Control postnatal muscle growth
How to measure whole body protein metabolism?
- urinary excretion of 3-methylhistidine (3-MH)
- Myosin and actin have histidine residues that are post-translationally modified with the addition of a methyl group
- 3-MH can not be reused and is quantitatively excreted in the urine on muscle breakdown
- usually expressed as a ratio of 3-MH to creatine
Exception: In Sheep, 3-MH is further metabolized and cannot to be used to measure protein breakdown
How to measure prenatal development
- figuring out how old the fetus is to project birthdate
1) somite formation - # = age
- mice and poultry
2) weight
3) length - crown to rump length (livestock)
- measured from poll to ischium of pelvis
4) anatomical indications - visual evaluation of gross developmental changes
- late phases will show this
GDF8 allele of Texel sheep is characterized by:
- by a G to A transition in the 3’UTR
- creates a target site for miRNAs
- > MyomiRNAs that are highly expressed in skeletal muscle
- This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep
- strongly expressed in skeletal muscle
- total level of circulating myostatin was 1/3 of that in wild type sheep although mRNA levels were unaffected
Pluripotent Stem Cells
- can give rise to all cell types of the body, but not placental cells
- embryonic stem cells
Myogenesis Summary
- prenatal formation of skeletal muscle
- Muscle mass is determined by number and size of muscle fibers
- During myogenesis, extent of muscle multiplication largely determines number of muscle fibers
- MRFsand PAX3/7 control the process
- MyomiRNAs are also involved
- Muscle fiber number is set before birth!
- > Postnatal growth(after myogenesis) is hypertrophy of existing fibers
Estrogen receptors Role in Control of Cartilage Maturation (Growth Plate)
- Pubertal growth spurt and cessation of growth are induced by sex hormones
- causes a pubertal growth sport (causes people to
reach maturation earlier and cessation)
Osteogenic cell
- develops into osteoblast
- stem cell
How does bone form through fetal development?
- Throughout fetal development and into postnatal growth and development, bone forms on the cartilaginous matrix
- By the time a fetus is born, most of the cartilage has been replaced with bone
- Some additional cartilage will be replaced throughout childhood, and some cartilage remains in the adult skeleton
Inheritance of double muscling
- Gene responsible for double muscling phenotype has
been mapped to chromosome 2 - Named mh for muscular hypertrophy
- DM phenotype occurs in the homozygous
recessive condition (mh/mh) - Heterozygote (mh/N) exhibits some increase
in muscle mass and has less negatives
What is the largest muscle tissue in an animal
- longissimus thoracic et lumborum
- accounts for 10% of total muscle weight
Tissues
- closely associated with cells and cell products that act synergistically to perform specific functions
I band in a sarcomere
- isotropic, light band
- region which only contains thin filaments
Perirenal (PR) Adipose Depot
- fat deposited around the kidney
White Adipose Tissue (WAT)
- primary site of energy storage (stores lipids)
- most common fat cell, used to store fat and found beneath the skin and abdomen
- adipocytes, specialized cells devoted to the accumulation of triglycerides
- contains triglycerides that are formed from free fatty acids and released from lipoproteins in bloodstream
- other metabolites accompany the fatty acids into the adipocyte which are required for de novo fatty acid synthesis
Satellite Cells
- Quiescent or dormant cells found between
basement membrane and sarcolemma in adult or
postnatal skeletal muscle - Source of nuclei for postnatal muscle growth
- Important for muscle repair!!
- muscle satellite cells play a crucial role in postnatal muscle growth (fuse with existing muscle fibers and provide the nuclei needed for postnatal fiber growth)
- muscle hypertrophy in postnatal growth
Costamere
- myofibrillar protein
- anchors myofibrils to sarcomere
- floods calcium into the cell
How are muscle fibers classified
- classified based on speed of contraction and type of metabolism
- differs based on muscle fiber types
- Type 1 (primary fiber development of myogenesis)
- Type 2A, 2X and 2B(secondary fiber development)
How has animal production and growth changed in animal markets?
- increased the size of the animals, but with more muscle and less fat
Diaphysis
- shaft region of bone
- cartilage becomes bone
- bone ossification(grows length of bone)
IGF-1 Role in Control of Cartilage Maturation (Growth Plate)
- Stimulate proliferation of chondrocytes
Adipocyte Growth
- Postnatal adipose tissue growth is an increase in the number of adipocytes (Hyperplasia) and an increase in the size (hypertrophy)
- 70% due to increase in cell diameter and volume
- 30% due to increase in cell number
- hyperplasia continues through postnatal growth
- > grows in waves, increase cell number followed by an increase in volume
Adipocyte transcription Factors (MRFs of the fat cells)
- Peroxisome proliferator activated receptor (PPARy)
- transcription factor that binds to the fat specific enhancer present in the adipocyte fatty acid - CCAAT-enhancer binding protein (C/EBP)
- C/EBPa and PPARy appear to act synergistically by triggering the adipocyte differentiation program and reciprocally activating transcription of one another - Reinoic Acid (RA)
- WNT
Types of Genetic Mutations in Muscle Growth
- Myostatin
Double muscled animals
A. Piedmontes and Belgian Blue have mutations in myostatin gene (complete KO)
B. Texel has reduction in active myostatin due to miRNA mutation
C. Dogs are homozygous for mutation(2 copies) - Callipyge
- miRNA involved
- unique inheritance pattern (heterozygotes that inherit gene from sire/dad)
- specific muscle hypertrophy that becomes evident after birth
- prevents normal down regulation of key genes (DLK-1, PEG-11)
A band in sarcomere
- antisotropic, dark band
- length of thick filament and contains thin filament(actin) that overlaps the thick filament(myosin)
TGF-beta Super Family
- inhibits proliferation of satellite cells
- causes prenatal muscle growth rates in adults*
- knockout of myostatin, increases muscle fiber hyperplasia
ex: Double Muscled Cattle - loss of active myostatin causes increased muscle fiber hyperplasia and double in muscle size
Abdominal Fat Pad (poultry) Adipose Depot
- within the body cavity, under the skin
2 populations of somitic cells
1) Dermomyotome
- form dermatome and myotome
- dermatome-> cells responsible for forming dermis
- mytome-> cells responsible for developing all muscles of the body
2) Sclerotome
- form vertebral column
Buttons
- Cartilaginous ends of the thoracic vertebrae in cattle
- with age, Ossification starts from the center and works outwards
- Evaluate top 3 buttons anterior to the 12th rib
- Also look at the lumbar region for ossification (work posterior to anterior)
True growth
- increase in structural tissues (bone, muscle and connective tissue)
What do bones need to grow?
- Bone contains Calcium and Phosphorus in an 2:1 ratio
- You want double the amount of calcium to phosphorous
- Most recommendations are to feed Ca:P at 2:1 ratio
- You find most feeds don’t have lots of calcium, they are majority phosphorous, so in order to make the 2:1 ratio of calcium to phosphorous then you can add limestone
- Magnesium and Vitamin D are necessary for proper growth
Paranemin and Synemin
- myofibrillar protein
- bind and stabilize myofibril to myofibril interactions
How do satellite cells increase muscle fiber growth
- Proliferate slowly(make multiple cells)
- Differentiate into myoblasts
- Fuse with existing fibers
- Purpose to either increase DNA content per fiber or
replace nuclei that are no longer functional - Minimum number must be maintained to ensure
regenerative potential in mature muscle - satellite cells decrease as muscle grows into adulthood, there is a much larger number at birth
Embryonic growth in meat animals
- meat animals spend a majority of their existence in the prenatal stage
- development of all tissues begins at fertilization
Heritability and selection to help feed the growing population
- animal growth and carcass traits have high heritability
- look for animals with faster rates of growth and utilize those animals
- identify superior genetics and use animals with those
Reserve Zone of Epiphyseal Growth Plate
- The reserve zone is the region closest to the epiphyseal end of the plate and contains small chondrocytes within the matrix
- These chondrocytes do not participate in bone growth but secure the epiphyseal plate to the osseous tissue of the epiphysis
3 Types of Adipose Tissue
- Brown
- White
- Brite (brown IN white), or Beige
Elastin fibers
- embedded in mucopolysaccharide ground substance
- > chondroitin sulphates most important
- rubberlike
- capable of being stretched to nearly twice their length
Perimysium
- surrounds muscle bundle in skeletal muscle
Sir John Hammond
- pioneer in animal growth research
- documented that the growth of animals produces tissues that accumulate in a sigmoidal manner
- showed that different tissues and organs grow at different rates and mature at different times
Purpose of Skeleton
- provides structural support for the body
How does Adipocyte Hypertrophy Occur
- occurs through the accumulation of triglycerides in the adipocytes
1. Incorporation of dietary fatty acids
2. De Novo Fatty Acid Synthesis - “from scratch”
- utilization of precursors to synthesize fatty acids
3. Lypolysis - non-esterified free fatty acids
- release of glycerol is best measure of the rate of lypolysis
Secondary Myotube Fibers
- Smaller, develop on the framework of the primary fibers
- influenced by maternal nutrition (runt pigs have lower number of secondary fibers)
- 80-90% of myofibers present at birth are derived from secondary fibers
- fetal phase
- muscle fiber types 2A, 2X and 2B evolve
Can We Accelerate Marbling Deposition? Study
- Timing of Exposure to high concentrate diet(conc)
- found that when ate conc-conc had highest marbling deposition
- conc-forage had second best
- forage-conc third
- forage-forage lowerst
3 types of muscle
1) skeletal
2) smooth
3) cardiac
Adipogenesis
- includes proliferation, differentiation and conversion of cells into lipid-filling cells (adipocytes)
1. Fertilized Egg
2. Fibroblast/adipoblast (determination)
3. Preadipocyte (differentiation)
4. Adipocyte
Runts
- Common in litter bearing animals
- While in utero restriction of nutrient supply to the developing fetus (maternal nutrtion/nutrient delivery to the fetus)
-> can alter muscle fiber development - Limited blood supply to the fetus caused by poor uterine position
- Has a low birth weight compared to others
- Has lower postnatal growth
- produce carcasses with less muscle and more fat
- there is a reduction in secondary to primary muscle fibers
Ex: Runt Pig
Carcass Maturity Classification
- Growth plate closure determines maturity in lamb carcasses
- > used to determine age of carcass for grading
- During processing, feet are removed at distal end of metacarpal
- If less than 12 months of age, epiphyseal cartilage is present and it “breaks” at distal epiphyseal plate
- if over 12 months of age, epiphyseal cartilage is ossified and foot separates at metacarpophalangeal joint, “Spool joint”
- In beef, ossification of vertebral column determines skeletal maturity
- > Sacral –lumbar –thoracic (posterior to anterior)
Mesenteric (MS) Adipose Depot
- around intestines
Myostatin
- Discovered that GDF-8(myostatin) is a negative regulator of muscle growth(prevents from growing too much muscle and not enough fat)
- inhibits myogenesis (cell muscle growth and proliferation)
- if do not have enough myostatin animal will have little body fat and EXCESSIVE MUSCLE
- detected early in the myotome
- continued expression in adulthood
- located in the cytoplasm of muscle fibers
- myostatin expression occurs during periods of primary and secondary fiber formation
- Myostatin also involved in muscle homeostasis during
adulthood
-> May inhibit satellite cell proliferation
Subcutaneous (SC) Adipose Depot
- fat deposited under the skin or hide
- pigs predominantly deposit here
- ruminants
Tibial dyschondroplasia (TD)
- Seen in poultry predominately, ~50% of broiler chickens have this problem
- Growth plate cartilage accumulates in proximal region of tibia and femur
- Getting too much cartilage and not enough none formation, you don’t have enough structural support
- Lameness, increased fractures in fibula, and increased susceptibility to osteomyelitis
- growth plate cartilage is not properly degraded and accumulates at the expense of bone formation
Maintenance Energy Requirement
- 15-25% of energy intake by animals is used to replace muscle protein that is degraded
- replacing proteins that are turned over each day