The Impact of Intramuscular Fat Accumulation on Osteosarcopenia

This report delves into the connection between intramuscular fat (IMF) accumulation and osteosarcopenia, a syndrome characterized by the loss of skeletal muscle mass, strength, and bone weakness. It explains that IMF, or intramyocellular lipid, stored within skeletal muscle fibers, can lead to health issues like obesity, insulin resistance, and osteosarcopenia when accumulated in excess. The report discusses the pathogenesis of osteosarcopenia, highlighting how IMF accumulation activates the p53-dependent signaling pathway, leading to muscle loss. It further elaborates on the roles of adipocytokines, fatty acids, and genetic factors in the development of the condition, and the importance of hormonal and nervous crosstalk in maintaining bone and muscle health. The diagnosis of osteosarcopenia involves assessing bone mineral density (BMD) T-scores, DXA tests, and skeletal muscle index measurements, and identifying intramuscular fat deposition. Finally, the report emphasizes the impacts of IMF accumulation, including sarcopenic obesity, inflammation, and oxidative stress, and suggests preventive measures like a quality diet, physical activity, and adequate protein and vitamin D intake.

0
Advanced nerve and muscle physiology
Advanced nerve and muscle physiology
Intramuscular fat accumulation causes osteosarcopenia
JUNE 2, 2019
Student Details:

1
Advanced nerve and muscle physiology
Contents
Introduction......................................................................................................................................2
Intramuscular fat accumulation causes osteosarcopenia.................................................................3
Pathogenesis of osteosarcopenia..................................................................................................4
Diagnosis of the osteosarcopenia.................................................................................................6
Impacts of intramuscular fat accumulation cause osteosarcopenia.............................................7
Conclusion.......................................................................................................................................8
References........................................................................................................................................9

2
Advanced nerve and muscle physiology
Introduction
Intramuscular fat (IMF) is located inside skeletal muscle fibers. This fat is stored inside the lipid
droplets in the close proximity of the mitochondria and would work as energy store during the
time of exercise. However, the excess accumulation of the IMF in the body would cause the
syndrome like obesity, insulin resistance, and osteosarcopenia. This would be increased due to
the deficiency of the estrogen in the body, glucocorticoids exposure, and mechanical unloading.
It may lead to mortality in the peoples (Hamrick, et al., 2016).
Osteosarcopenia is the syndrome causing loss of skeletal muscle mass and strength and bone loss
and weakness. The T-scores of the bone, in the bone mineral density (BMD) criteria identified
by the World Health Organization (WHO) a range of being diseased from the disorder named
osteosarcopenia get discussed. When BMD would get lower than -1 than it would be osteopenia
and lower than -2.5 it would be osteoporotic (Hassan & Duque, 2017).
Here discussion would be enlightened on the intramuscular fat accumulation causes
osteosarcopenia. During this discussion IMF and its accumulation inside the body followed by
the pathophysiology of osteosarcopenia and by the impacts of the intramuscular fat accumulation
on the osteosarcopenia.

3
Advanced nerve and muscle physiology
Intramuscular fat accumulation causes osteosarcopenia
Embryonic mesoderm is the germ layer from where bone, muscle, and fat would be derived.
Intramuscular fat (IMF) would also be known as intramyocellular (IMC) lipid. A deposition of
adipocytes in the muscles is known to be intermuscular adipose tissue. This intermuscular
adipose tissue would get situated in between bundles of muscles. Infiltration of lipid in
myofibers is known as intramuscular fat. This intermuscular adipose tissue and intramuscular fat
would be increased during the aging and sarcopenia. Due to which inflammation and functional
deficits in skeletal muscle would get occur due to the increment in the intermuscular adipose
tissue and IMF inside the body (Saedi, et al., 2019).
Increment in the levels of marrow adipose tissue at a higher level would be responsible for the
leading of the loss of bone and for the osteoporosis disorder. It would lead to the osteoporosis
due to the secretion of the adipocytokines and fatty acids. These adipocytokines and fatty acids
would be toxic for the cells situated inside the vicinity of adipocytes and lead to the decrement in
the formation of the bone and increment in the resorption of the bone tissue. When the bone
resorption process takes place, then the tissue presents inside the bones would get break down by
osteoclasts and the minerals inside the tissue would be released outside the bone tissue. The
releasing of the minerals outside the tissues would lead to the transfer of the calcium inside the
blood from the tissues of the bone (An, et al., 2016).
Due to intramuscular fat deposition in the skeletal muscle fibers would initiate and activate p53-
dependent signaling pathway, which would lead to the loss of muscle mass and strength and lead
to osteosarcopenia (Conte, et al., 2013). Deficiency of Lipin1 gene in the human would lead to
the development of the adipocytes, which would not be mature adipocytes. Deposition of the

4
Advanced nerve and muscle physiology
intramuscular fat would take place in the humans due to the expression of Perilipin 2 (PLIN2) in
the higher amount than the normal (Hausman, et al., 2014).
Protein synthesis would be able to enhance the hypertrophy of muscle and would be helpful in
the maintenance of the strength of muscle. However, due to impaired protein formation would
lead to the atrophy of muscle. Insulin is the factor, which would lead to strengthening the skeletal
muscle and deposition of muscle adipocytes. However, the accumulation of intramuscular fat
would lead to the decrement in the sensitivity to insulin and provide decrement in the impairing
capacity of the insulin synthesis. The decrement in the sensitivity of insulin along with the
infiltration of the fat inside the body would lead to providing an effect on the strength and mass
of the muscle. Due to injury in the muscle, which would get prolonged and would be replaced by
the fatty and fibrous tissue at the place of the lost muscle fibers. Due to this replacement by
fibrous and fatty tissue would lead to the weakness in the muscle (Hamrick, et al., 2016).
Pathogenesis of osteosarcopenia
Bone and muscles would be strongly united organs with each other for the sharing of the critical
functioning during the structure formation, motion and providing strength combinedly. These
both are the very active tissues in the metabolic functioning inside the body. Due to degradation
in the bone and muscles, the formation of the protein inside the skeletal muscle would get
balanced while the reabsorption process in the bone and muscles would provide equilibrium in
the formation of the bone (Bruyere, et al., 2017).
BMD would be lowered down due to the imbalance placed in the functioning of these tissues and
lead to sarcopenia to the person. These tissues named bone and muscles would get stimulation
from the endocrine stimulated hormone during their functioning in the body. They would also
produce hormones that would provide impacts on the functioning of the other tissues and the

5
Advanced nerve and muscle physiology
metabolism activity. These tissues would be helpful in sustaining homeostasis in the correlative
communication with the adipose tissues in the body of a person. The help of hormonal and
nervous crosstalk would provide this homeostasis. Any misbalance in this crosstalk would
provide an effect on the bone, muscles and adipose tissues (Paintin, et al., 2018).
Osteosarcopenia would be affected due to endocrine disorders named vitamin D deficiency,
diabetes, abnormal functioning of thyroid and obesity, corticosteroids use. The Loss of bone and
muscles would be associated with the genetic polymorphism of the genes, and proteins. The
genes named GLYAT, methyltransferase-like 21C, and proteins named myostatin, α-actinin 3,
myocyte enhancer factor 2C and proliferator-activated receptor gamma coactivator 1-alpha
would get included in the genetic polymorphism. The help of decrement in the proliferation of
the myoblast would inhibit muscles growth. This inhibition of the muscles growth would be
affected by the myostatin (Arazi & Eghbali, 2018).
During the mechanical functioning, bone and muscles would amend their mass and strength due
to their adaptive nature. Because of this adaptive nature of both bone and muscles, it would be
necessary to get stimulus for the mechanical functioning to maintain mass and strength in the
bone and muscle for the good health of them. Due to facilities to working off all functioning by
machine, physical working would get decrease. This decrement in the physical movement would
lead to the degradation of muscle and resorption of the bone. Due to this, the fat deposition
would be leaded in the bone and muscles both and infiltration of the fat in the bone and muscles
would begin to take place. This would lead to osteosarcopenia to a person (Rahemi, et al., 2015).
This infiltration of fat would lead to a process named lipotoxicity. In the lipotoxicity process,
inflammatory cytokines secretion would take place from the fat inside the bone marrow and body
of a person. Due to this, tumor necrosis factor alpha, interleukin-6 and inflammatory cytokines

6
Advanced nerve and muscle physiology
would be secreted in the high concentration of these serums in the body of the person having
osteosarcopenia. Mass of muscles would fluctuate with the fluctuations in the mass of the bone
in the body of a person (Hirschfeld, et al., 2017).
Diagnosis of the osteosarcopenia
Due to the osteosarcopenia, the quality of the life of the patient would be depleted. Loss of bone
would be caused to the person having osteoporosis. Due to the loss of bone patient would be
suffered from the situation of endless pain. Due to the osteoporosis, the density of bone would be
decreased because of mineral loss in the bones of the patient. It would lead to the weakness and
brittleness in the bones of the patient. Due to the brittleness in the bones, it would lead to the
fracture due to the fall or due to the mild stresses like a cough. In the situation of being
osteoporotic, the new bones would not replace the loss of bone in the body. The symptoms of the
osteoporosis would be observed due to the weakness in the bones. Due to this, back pain would
be caused by the fractures, height loss, the posture of the body would be stooped and fracture in
the bones would be caused very easily from the expectation (Staff, 2016).
Sarcopenia is a disorder, which would lead to the loss of the muscles mass in the body of the
person. Due to the decrement in the muscles mass due to loss of muscles mass, it would lead to
the weakness in the muscles in the body of the person. It would cause to the muscles due to the
decrement in the production of the protein. Because the production of protein in the body would
be decreased which would lead to the growth of the muscles in the body of the person. Due to a
decrement in the hormones named testosterone and insulin-like growth factor would also lead to
the loss of muscles mass and strength. It would lead to the decrement in the size of the muscles,
weakness, and lack of balancing means fall due to imbalance. These consequences to the patient
having osteosarcopenia would lead to the mortality in the patient (Delmonico & Beck, 2017).

7
Advanced nerve and muscle physiology
For the diagnosis of the osteoporosis, T-score in the bone density test and DXA test would be
performed. In this test, the help of the X-rays would calculate grams of calcium and minerals in
the square centimeter of the bone. DXA test would be performed to test that at what place in the
body fractures in the bone would take place most often (Staff, 2017). For the diagnosis of the
sarcopenia, DXA and BMD test and skeletal muscle index would be measured and for the
identification of the intramuscular fat deposition, mean muscle attenuation would be analyzed
(Fujiwara, et al., 2015).
Impacts of intramuscular fat accumulation cause osteosarcopenia
Due to intramuscular fat accumulation in the body loss of bone mass and strength would take
place. Due to this fat deposition, a health issue named sarcopenic obesity would be diagnosed.
Due to increment in the adipose tissue in the body, growth hormone and insulin-like growth
factor would be decreased. It would lead to inflammation in the body. The decrement in the lipid
oxidation would lead to increment in the intramuscular adipose tissue during the infiltration of
the fat. It would lead to the decrement in muscle mass and muscle strength. In the bone,
decrement in the reactive oxygen species production would lead to the decrement in the
osteoblast activity and increment in the osteoclast activity. This would lead to the decrement in
the density of the bone and loss of the bone. These issues in the body would lead to the
increment in the oxidative stress, resistance of insulin and decrement in the expenditure of the
resting energy (Ormsbee, et al., 2014). It would be prevented by the taking effective quality of
diet instead of a low-quality diet (Ahmed, et al., 2018). Exercises to perform physical activity, a
proper amount of protein and vitamin D would be helpful in the prevention of osteosarcopenia
(Hita-Contreras, et al., 2015).

8
Advanced nerve and muscle physiology
Conclusion
Intramuscular fat would be found in the skeletal muscle fiber deposited in the lipid droplets.
When the intramuscular fat would be accumulated in the excess amount then it would lead to
disorders like osteosarcopenia. Due to excess deposition of intramuscular fat, loss of muscles
mass, strength, and loss of bones would take place in the body of a person. It would take place
due to the increment in the osteoclast activity in the bones and decrement in the lipid oxidation in
the muscles. Due to lipid oxidation in the tissues, intramuscular fat accumulation takes place. It
would lead to weakness in the bone and muscles with the painless situation. It would lead to the
chances of fall, fractures, the problem in walking and may increase the chances of the mortality
in the population. To prevent excess intramuscular fat deposition, the quality diet having vitamin
D and protein in the effective amount and physical activity would be helpful.

9
Advanced nerve and muscle physiology
References
Ahmed, S. et al., 2018. e Effects of Diet on the Proportion of Intramuscular Fat in Human
Muscle: A Systematic Review and Meta-analysis. Frontiers in Nutrition, 20 February.Volume 5.
An, J. et al., 2016. Natural products for the treatment of bone-erosive diseases: The effects and
mechanisms on inhibiting osteoclastogenesis and bone resorption. International
Immunopharmacology, July, Volume 36, pp. 118-131.
Arazi, H. & Eghbali, E., 2018. Osteosarcopenia and Physical. Annals of Sports Medicine and
Research, 20 April.5(1).
Bruyere, O., Cavalier, E. & Reginster, J.-Y., 2017. Vitamin D and osteosarcopenia: an update
from epidemiological studies. Current Opinion in Clinical Nutrition and Metabolic Care,
November, 20(6), pp. 498-503.
Conte, M. et al., 2013. Increased Plin2 Expression in Human Skeletal Muscle Is Associated with
Sarcopenia and Muscle Weakness. PLoS ONE, August.8(8).
Delmonico, M. J. & Beck, D. T., 2017. The Current Understanding of Sarcopenia. American
Journal of Lifestyle Medicine, 11(2), pp. 167-181.
Fujiwara, N. et al., 2015. Sarcopenia, intramuscular fat deposition, and visceral adiposity
independently predict the outcomes of hepatocellular carcinoma. Journal of Hepatology, 18
February, 63(1), pp. 131-140.
Hamrick, M. W., McGee-Lawrence, M. E. & Frechette, D. M., 2016. Fatty Infiltration of
Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity. Frontiers in
Endocrinology, Volume 7.

10
Advanced nerve and muscle physiology
Hassan, E. B. & Duque, G., 2017. Osteosarcopenia: A new geriatric syndrome. AFP: Australian
Family Physician, November, 46(11), pp. 849-853.
Hausman, G. J. et al., 2014. Intermuscular and intramuscular adipose tissues: Bad. Adipocyte,
3(4), pp. 242-255.
Hirschfeld, H. P., Kinsella, R. & Duque, G., 2017. Osteosarcopenia: where bone, muscle, and fat
collide. Osteoporosis International, 28(10), pp. 2781-2790.
Hita-Contreras, F., Martinez-Amat, A., Cruz-Diaz, D. & Perez-Lopez, F. R., 2015.
Osteosarcopenic obesity and fall prevention strategies. Maturitas, February, 80(2), pp. 126-132.
Ormsbee, M. J. et al., 2014. Osteosarcopenic obesity: the role of bone, muscle, and fat on health.
Journal of Cachexia, Sarcopenia and Muscle, September, 5(3), pp. 183-192.
Paintin, J., Cooper, C. & Dennison, E., 2018. Osteosarcopenia. British Journal of Hospital
Medicine, 2 May, 79(5), pp. 253-258.
Rahemi, H., Nigam, N. & Wakelling, J. M., 2015. The effect of intramuscular fat on skeletal
muscle mechanics: implications for the elderly and obese. Journal of The Royal Society
Interface, 12(109).
Saedi, A. A., Hassan, E. B. & Duque, G., 2019. The diagnostic role of fat in osteosarcopenia.
JLPM: Journal of Laboratory and Precision Medicine, Volume 4.
Staff, M. C., 2016. Osteoporosis. [Online]
Available at: https://www.mayoclinic.org/diseases-conditions/osteoporosis/symptoms-causes/
syc-20351968

11
Advanced nerve and muscle physiology
Staff, M. C., 2017. How osteoporosis is diagnosed. [Online]
Available at: https://www.mayoclinic.org/diseases-conditions/osteoporosis/in-depth/
osteoporosis/art-20304599