THE FAT CELL STORY
Introduction: Obesity and overweight are the most prevalent medical entities of modern time
and accounting for about two-thirds of the United States adult population and most other industrialized
countries. The consequence of these entities to the people health is quite serious, and, more than we realize.
We, as the humans have to do something to change
this trend otherwise our new generation health will be in jeopardy. What I want to do is to learn everything about the fat
cells and try to summarize it. So anyone want to live longer have to learn and understand this fact and trying to loose extra
fat that he or she does not need.
The fat cell, once upon a time believed to be a passive cells. It main role is
storing energy in the form of fat, although it also cushions and insulates the body.
Dduring the past fifteen years we discovered that the fat cells
produce a lot of chemicals that causes the so called diseases of civilization this including atherosclerosis, hypertension,
diabetes mellitus, cancer and arthritis. In order to cure above mention medical problems we must eliminate all excessive fat.
Here is the summary of the content on the subject
that will be discussed.
THE FAT CELL
(please click below)
http://www.lifespan.org/adam/healthillustratedencyclopedia/2/19267.html
Where and how the fat cells come
from?
The journey from one cell to 40
billion cells
Adipogenesis: The development of adipose tissue or the formation of
fat or fatty tissue.
The fat cells or adipocytes are differentiated from adipoblast: the: Pluripotent mesenchymal embryonic stem cells of the adipose tissue to become preadipocytes. This occurs during gastrulation when mesoderm layer is formed or about 3 weeks old or at the human embryo Carnegie stage7.The preadipocytes then differentiate to be mature adipocytes under
control by many factors. This process occurs through out life. In the adipose tissue, therefore contain many stages of adipocyte
from adipoblast, adipocyte, young adipocyte and mature adipocyte. The mature adipocytes also vary in size depend on fatty
acid content. The functions of adipocytes also vary depending on the age and size of individual adipocyte.
After the adipose tissue forming in the third week of pregnancy, it continue to differentiate
and distribute throughout the body slowly until the third trimester of pregnancy(29 week),this process accelerated rapidly
under the influence of growth, and sex hormones. At the 40 week, the body fat content will be about 15 % of body mass. If
the mother is diabetic and with poor control, the mother’s insulin level will be higher along with higher blood sugar.
The blood sugar that passes through the placenta will be higher and that will stimulates the fetus pancreas to excrete more
insulin. The higher insulin will increase the fetus fat content. That makes the fat mass higher than normal at the time of
delivery. The process of increasing fat mass during the last trimester is mainly due to increase in the size of adipocyte
Adipocyte differentiation:
Ideally the fatty tissue should distribute evenly under the skin or surrounding organs in order to cushioning and insulating
the body and lubricating the organs beside the main function of storing of energy in the form of fatty acids. However the
fat distribution is uneven by the control of the genes or transcription factors such as C/EBP, nuclear hormone receptors such as Ppar and other hormones, such as sex hormones, stress hormones such as cortisol, adrenalin,
growth hormone, insulin like growth factor1(IGF-1), insulin and certain fatty acids. Certain drugs such as TZD (thiazolidinediones), protease inhibitor and certain diseases such as AIDS can interfere with the fat distribution
and differentiation. The abnormal excessive fat distribution especially android or abdominal fat especially
visceral fat which can cause medical problems so called metabolic syndrome.
Normally once preadipocyte
differentiate to mature adipocyte, there will no further divide or die except in special circumstance that cause adipocyte
to die or call apoptosis. Preadipocyte, however can form from polypotent progenitor stem cell or fibroblast with the stimuli
such as MCSF (macrophage colony stimulating factor) which excrete from enlarged mature adipocyte, insulin, IGF-1, cortisol
as well from certain long chain free fatty acids and drug such as TZD
Adipocyte hyperplasia and hypertrophy:
When the people
gain weight usually is due to increase in the adipocytes (number) or increase the fat content in the adipocytes (size) or
both. As mentioned above, all types of fat cells exist at the same time throughout life. During the third trimester, however
the fat mass is increasing by increase in fat content rather increasing in the numbers. In the first decade of life, especially the first few years after birth the fat mass actually decrease
when compare with other body mass (small fat cells), the rest of the first decade the fat mass is increase due to increasing
in fat content (hypertrophy).In puberty period with influence of sex hormones and growth hormone, the number of fat cells
increase (hyperplasia). The growth hormone increase subcutaneous fat all over. The estrogen increase fat cells in the lower
or glutealfemoral area more than upper or abdominal area. In males, the testosterone stimulates muscle mass more than the
fat mass. However if the excess energy intake occur at any period of life the fat mass will increase by increase in size of
the fat cells. In males due to lack of adequate subcutaneous fat cells in lower region to accommodate extra fat. The fat cells
hypertrophy therefore occurs more obvious in upper body area than female counterpart so called apple shape (pear shape in
female). During post menopausal period, when estrogen decline, inadequate stimuli to estrogen receptor in the hypothalamus
at ventro lateral nucleus, the appetite increase that cause energy uptake more than expenditure. This create the fat deposit
in upper body because lower body reservoir already full (no new fat cells created due to lack of estrogen).
Fat
and body composition and body shape:
Ideal
adult body shape please click below
http://en.wikipedia.org/wiki/Body_shape
http://books.google.com/books?id=6UymxRxhX1AC&pg=PA210&lpg=PA210&dq=body+composition+essential+fat&source=web&ots=MMA4O3nZN3&sig=svghR2AxPuDZBqo0utcln4IcRMY#PPA207,M1
http://health-essential.blogspot.com/2007/06/do-you-want-to-optimize-your-body.html
Fat distribution
(please click below)
http://www.virtualfitnesstrainer.com/articles/Fat_Distribution.htm
http://en.wikipedia.org/wiki/Human_body
As mention above the percentage of fat mass depend on amount of food you eat
which depend on your basal metabolism and physical activity.If you eat more than you need or excessive energy
intake. Of cause you will gain fat weight.Recently it become very important that where the fat will be
distributed.This fat distribution is undercontrol by many factors especially the sex hormones.
Estrogen stores fat in the buttocks, thighs, and hips in women.[18][19] When women reach menopause and the estrogen produced by ovaries reduces, fat migrates from their buttocks, hips and thighs to their
waist,[20] later fat is stored in belly.[21] Thus females generally have relatively narrow waist and big buttocks, [22] and this along with wide hips make for their bigger hip section and lower waist-hip ratio, around 0.7
Estrogens increases fat storage in the body,[23] which results more fat stored in body of females. Body fat percentage recommendations are more for females, this serves as an energy reserve for pregnancy. Males have less subcutaneous fat in face due to effect of testosterone,[24] also testosterone reduces fat by aiding fat metabolism. Males generally deposit fat around waist and abdomen("apple shape") due to lack of estrogen. A central pattern of body fat, mainly seen in
males, seems to start in adolescence. Post menopausal women, abdominal adiposity is associated
with a relatively more androgenic sex
hormone profile. Treatment with ethinyl estradiol in M-F transsexuals induced a significant increase
in all subcutaneous fat depots, with a lesser but proportional and significant increase
in the visceral fat depot and a decrease in thigh muscle area. Testosterone administration
in F-M transsexuals markedly increased thigh muscle area, reduced subcutaneous fat deposition at
all levels measured, but slightly increased the visceral fat area. We conclude
that sex steroid hormones are important determinants of the sex-specific localization of body
fat.
Fat distribution in menopause woman: http://ije.oxfordjournals.org/cgi/content/abstract/20/1/151
Abdominal fat in long-term HRT users is lower
than that of non-users of similar age, menopausal age and body mass index.
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=10134&Ausgabe=225053&ProduktNr=223845
What kind or type of fat cell or
adipocyte we have?
There
are two types of adipose tissue exist: white adipose tissue (WAT) and brown adipose tissue (BAT),
which are also known as white fat and brown fat, respectively. White fat cells (also known as Unilocular Cells) contain
a large lipid droplet surrounded by a ring of cytoplasm. The nucleus is flattened and located on the periphery. The fat stored is in a semi-liquid
state, and is composed primarily of triglycerides and cholesterol ester.
Brown adipose tissue (BAT) or brown
fat is present in many newborn or hibernating mammals. Its primary purpose is to generate body heat. contain a single,
large fat vacuole, brown adipocytes contain several smaller vacuoles and a much higher
number of mitochondria. Brown fat also contains more capillaries since it has a greater need for oxygen than most tissues.At birth,
the brown fat, which then makes up about 5% of the body mass and is located on the back, along the upper
half of the spine and towards the shoulders, is of great importance to avoid lethal cold (hypothermia is a major death risk for premature neonates). The brown adipose tissue expressing the mitochondrial uncoupling protein 1 (thermogenin),) has the ability to dissipate energy through adaptive from Non-shivering thermogenesis by
giving the cell's mitochondria an ability to uncouple oxidative phosphorylation and utilize substrates to generate heat rather
than ATP. After exposure to cold leads to sympathetic stimulation of brown adipocyte via norepinephrine binding
to beta- adrenergic receptors. As in white fat, sympathetic stimulation promotes hydrolysis of
triglyceride, with release of fatty acids and glycerol. However, within brown adipocytes, most fatty acids are immediately
oxidized in mitochondria and, because of the uncoupling protein; a large amount of heat is produced.
In human adult, white adipose
tissue composes as much as 20% of the body weight in men and 25% of the body weight in women.However so called essential fat
for a man is 3 % and 12 % for a woman.
More detail please click on
http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/brownfat.html
Adipocyte As An Endocrine Gland
As mentioned before fat cells once believed to be benign cells with the
function of storage of excessive fat for the future use. Since 1994, obese gene (OB) discovered along with discovered of hormone
Leptin. Since then there are 50 chemicals or adipocytokines or adipokines were discovered. Here is part of the lists. (We
will keep add on to the list when we know more about them. These adipokines will be subjected for further discussion in the
future)
1...Leptin (http://en.wikipedia.org/wiki/Leptin )
2. Adiponectin (http://en.wikipedia.org/wiki/Adiponectin), anti-inflammatory factor
3. Tumor_necrosis_factor_alpha, the inflamatory factor http://en.wikipedia.org/wiki/Tumor_necrosis_factor_alpha )
4. Angiotensinogen, angiotensin II (http://en.wikipedia.org/wiki/Angiotensin_II )
5. Resistin (http://en.wikipedia.org/wiki/Resistin)
6. Interleukin-6 (http://en.wikipedia.org/wiki/Interleukin-6) , IL-1b. IL8, IL-10, IL- 17D
IL-18
7. Plasminogen activator inhibitor-1 (http://en.wikipedia.org/wiki/PAI-1 ), proclotting factor
8. Adipsin
9. Acylation -stimulating protein
10. Agouti protein
11. Transforming growth factors -b
12. Adipophilin
13. CRP, the inflammatory protein marker
14.11beta-hydrxysteroid dehydrogenase-1(converts
circulating inactive cortisone to active cortisol)
15. Adipose aromatase (converts circulating androgens
to estrogens)
16. MCP-1 monocyte (macrophage) chemo attractant
protien-1
17. Visfatin
18. Growth-regulated oncogene (GRO)
19. Macrophage
inflammatory protein (MIP)-1α and -1β,
20. Tissue inhibitor
of metalloproteinase (TIMP)-1 and TIMP-2 (37). TIMPs
21. NEFA (Nonesterified fatty acid)
22. MCSF (macrophage colony
stimulating factor)
ADIPOCYTE APOPTOSIS
Some experts believe
the fat cells never die in normal situation. However a few chemicals, foods and certain drugs can cause adipocyte apoptosis.
Because obesity basically due to either enlargement of the fat cells and increasing of the number of the fat cells. In order
to eliminate excessive weight effectively, it make sense to get rid of the fat cells along with the reduction of the fat content
from the fat cells by using it as the energy. Therefore the study of adipocyte apoptosis is very important in the treatment of obesity and/or osteoporosis, with special emphasis
on natural products as promising leads for drug development. The following chemical compounds had been studied and proved
to be effective in induce adipocyte apoptosis. Here are the lists of those compounds:
-
Leptin treatments on rats
are suppressed food intake, reduced body weight, reduced body fat, adipocyte apoptosis, and elevated energy expenditure. Further,
leptin treatment of leptin-deficient (ob/ob) mice increases endosteal bone formation and bone mineral
-
Ciliary neurotrophic factor
(CNTF)
-
Beta adrenergic agonists
-
Conjugated
linoleic acid (CLA)
-
Tumor necrosis factor-alpha
(TNF-), Adipocyte apoptosis has also been induced in vitro using tumor necrosis factor-alpha (TNF-),
-
Epigallocatechin gallate
(EGCG) from Camellia sinensis (tea)
-
Ajoene, from Allium sativum. Natural products have potential for inducing apoptosis of adipose tissue, inhibiting bone marrow adipogenesis
and increasing the expression of osteogenic factors in bone, thereby yielding effective treatments for obesity and osteoporosis
-
Some PPAR gamma ligands
-
Vitamin A in higher doses
-
Prostaglandin metabolites
such as prostanoid (15dPGJ2)
-
High dietary calcium intake
-
Omega 3 fatty acid
-
Hot pepper: Treatment with capsaicin decreased the number of normal cells and increased
the number of early apoptotic and late apoptotic cells in a dose-dependent manner. The treatment of cells with capsaicin caused
the loss of mitochondria membrane potential (m). The induction of apoptosis in 3T3-L1 preadipocytes by capsaicin was mediated
through the activation of caspase-3, Bax, and Bak, and then through the cleavage of PARP and the down-regulation of Bcl-2.
Moreover, capsaicin significantly decreased the amount of intracellular triglycerides and glycerol-3-phosphate dehydrogenase
(GPDH) activity in 3T3-L1 adipocytes. Capsaicin also inhibited the expression of PPAR, C/EBP, and leptin, but induced up-regulation
of adiponectin at the protein level. These results demonstrate that capsaicin efficiently induces apoptosis and inhibits adipogenesis
in 3T3-L1 preadipocytes and adipocytes.
-
Antiretroviral
therapy (ART). With nucleoside analogue reverse transcriptase inhibitors (NRTIs) in general and stavudine in particular. The
exact mechanism of fat wasting remains unclear, but the pathogenesis can largely be attributed to the mitochondrial toxicity
of NRTIs. NRTIs are inhibitors of polymerase gamma, an enzyme which is necessary for the replication of mitochondrial DNA
(mtDNA). Dysfunction were identified in the subcutaneous fat tissue and skeletal muscle of HIV-patients under ART and linked
to the use of stavudine.
Note: the detail can be reviewed
on the references section
Vitamin A and adipocyte
apoptosis: http://jme.endocrinology-journals.org/cgi/content/full/35/2/391
Omega 3 fatty acid:
http://jn.nutrition.org/cgi/content/full/136/12/2965
-
TGF is an endogenously
produced hormone-like substance that plays a role in fat cell apoptosis (cell death). In times of starvation, such as long
term carbohydrate depletion, adipose tissue produces TGF as a means of blocking fat cell anabolism, this means insulin in unable to trigger fat cell growth yet still possesses its powerful
anabolic signal for muscle. This in turn facilitates the process of fatty
acid mobilization (release from adipocytes/fat cells) and subsequent utilization as an energy source for the body. The result
is fat cell starvation and eventual apoptosis. This is synergistic with natural PGF-2 elevation since localized increases
in PGF-2 also result in an increase in TGF production. There also appears to be correlation between endogenous /exogenous
GH levels and TGF. The higher the GH level, the more TGF produced in/by adipose tissue. This somewhat explains the extreme
fat loss that occurs during GH administration even without a change in dietary habits.
Bodybuilders utilized exogenous
forms of TGF as a means of fat cell eradication. Picture the number of fat cells in an athlete's body decreased by 20-50 %!
During administration, fatty acids provide food for hard training muscle. Post administration, the athletes possessed a much
lower potential for gaining fat tissue while creating a superior ability to utilize calories to build muscle. Simply stated,
this means less mouths (cells) to feed = more calories for muscular repair and growth. Obviously there was a synergistic chemistry
possibility utilized by athletes. TGF alone would be catabolic to lean mass tissue so an increase in the Adipose tissue mass
is reflected by the volume and the number
of adipocytes and is subject to homeostatic
regulation involving cell death mechanisms. In this study we have investigated the mechanisms of apoptosis in human preadipocytes and adipocytes that may play
a role in the regulation of adipose tissue mass.
We found that death receptors (CD95, TNF-related
apoptosis-inducing ligands receptors 1 and 2, and TNF receptor 1) are expressed in human fat cells and that apoptosis can be induced by specific ligands. Sensitivity
to apoptosis could be stimulated by an
inhibitor of biosynthesis. In addition,
inhibition of auto-/paracrine action of IGF-I dramatically sensitizes human adipocytes for death ligands-induced apoptosis. Phosphoinositide 3-kinase and, to a weaker
extent, p38 MAPK are involved in IGF-I-mediated
survival. IGF-I protect human fat cells
from apoptosis by maintaining the expression of antiapoptotic proteins, Bcl-xL and Fas-associated death domain-like IL-1-converting enzyme inhibitory protein. In conclusion, we identified mechanisms of apoptosis induction in human fat
cells. We furthermore demonstrate that human fat
cells protect themselves from apoptosis
by IGF-I in an auto-/paracrine manner.
Leptin-induced
adipose apoptosis: Implications
for body weight regulation
http://www.nano.uga.edu/pdfs/BaileGullicksen.pdf
Adipocyte Evolution
For hundred thousand years since human race exist, we almost always struggled to overcome
food scarcity, disease and hostile environment. We were in the stage of famine more often than the stage of feast. Our body
prepare for this stage of famine in order to survive so called starvation mode. During this period possible certain genes
expression such as Sir2 and SCH9 genes that prepares our body for this famine stage. This means that our body prepares to
survive better than other stage. However after world war two the food become plentiful when we start to eat more than usual
and more than the body need, another survival gene or diabetic gene begin to work by convert everything to fat very efficiently
in order to prepare for the next famine period. That make majority of us become overweight or obese and eventually succumb
diabetes along with cardiovascular disease and cancer and other chronic diseases that we know of.
A total of 99% of the world’s metazoan species rely solely on
innate immunity to defend them from infection. For insects, an organ called the fat body mostly mediates
this response. The fat body has a receptor for bacterial and fungal cell wall constituents
called the Toll receptor. This receptor activates the nuclear factor kappa B (NF-kappaB) signaling
cascade and induces the secretion of antibacterial peptides and other defense mechanisms.
The insect fat body simultaneously manages the animal’s liver functions and the
storage of lipids. At some point during evolution, vertebrates split these metabolic duties between
the liver and adipose tissue. But what happened to the functions of innate immunity?
Since the discovery of innate immunity and the acute phase response in humans, it has been thought
that these functions were primarily the domain of the liver, but more recent
evidence shows that when fat storage was delegated to adipose tissue, the ability to fulfill some
aspects of innate immunity was preserved in adipose tissue as well. The white adipose tissue and
bone marrow also share an embryologic origin.
When adipose tissue is increase in size and number
of adipocytes. The adipocytes therefore increasing expression of the innate immunity like bone marrow and liver by excreting
more inflammatory moecules. This is more likely
Will be the reason for the etiology of the so
called diseases of civilization.
Adipose tissue as innate immune system http://circres.ahajournals.org/cgi/content/full/96/9/939
Sir2 gene :http://hubpages.com/hub/Sir2_Gene
Sir2: http://en.wikipedia.org/wiki/Sir2
SCH9 gene: http://www.sciencemag.org/cgi/content/abstract/292/5515/288
starvation mode http://www.unu.edu/unupress/food2/UID07E/uid07e11.htm
ADIPOSITY AND HUMAN LONGEVITY
Introduction: It has been recognized the danger of obesity some over 2000 years ago. The Greek physician Hippocrates
observed that “Sudden death is more common in those who are naturally fat than in the lean”. There was no documentation
related to the weight problems and human longevity until around 1913 Medico-Actuarial Mortality Investigation published the
article which covered data from 1885 to 1909, when tuberculosis and pneumonia were the leading causes of death. The study
indicated that the lowest mortality rate by build were found in persons whose weight at the younger ages somewhat over weight
for the insured population, and the persons whose weight at older ages was under the average. After 1913, however the mortality
investigations conducted by life insurance companies showed that, in general, persons whose weights were below average lived
longer than those whose weights were above average. In 1942 and 1943 Metropolitan Life developed an ideal weight table which
revised again in 1983 and called 1983 Metropolitan Height and Weight Tables which still in used in present day.
However the mechanisms of excessive body fat weight affect human longevity is not known until
-1959 The report of the Build and Blood Pressure Study indicated
the relationship of high blood pressure and overweight.
-1973 the American Cancer Society reported the finding of
study some 750,000 people since 1959. The study showed that the lowest mortality rate was lowest in nonsmokers with weighing
80 % to 89 % of average weight.
-1977 MANITOBA STUDY with 26 years observation
period found the relationship of excessive body weight and ischemic heart disease.
-1981 Report in Am J Epidemiology (1981; 113:144-56).
Contributions of obesity and diabetes in Pima Indian
-1983 the Framingham Heart Study reported in the cohort of
5209 men and women which had been follow up since 1949 , found the positive relationship of overweight and cardiovascular
disease, hyperlipidemia.
- 1985 the report from Annual of Internal Medicine(
1985; 103:1034-6) on the prospective American Cancer Society study followed 750,000 men and women for 12 years showed increase
in incidence of cancer in overweight men and women were higher than normal weight.
-1988 Reports on Framingham study
related to central fat distribution and the risk of coronary heart disease.
In the recent studies in Annuals of Internal Medicine January 2003 showed that the people whom
gaining weight during midlife are the higher mortality than normal weight. The overweight nonsmoker’s female lost 3.3
years of life expectancy for female and 3.1 years for male. For obese nonsmoker people, female lost 7.2 years and 5.8 years
in male. However If obese and smoke as well will lost 13.3 and 13.7 years in life expectancy in female and male respectively.
In 2005 in The New England Journal of Medicine(March17,05) the study report predicted that life
expectancy will decline over the next 50 years by at least two to five years due to the epidemic of obesity in United
States. It will be the first time since the past 1000 years that human life expectancy is decline.
Note: In diabetic men or women age 50 and old died on average
7.5 and 8.2 years earlier respectively, than those who did not have diabetes. If diabetic with cardiovascular disease
will reduce life expectancy by 7.8 years for men and 8.4 years for women.
As long as mechanism of adiposity that cause cardiovascular diseases, it easy to understand due
to current knowledge which we know that adipocytes are the endocrine glands that produce chemicals that cause inflammation,
insulin resistance that lead to atherosclerosis and diabetes. In cancer however, hard to explain but the most likely
is the combination of increase in estrogen production by adipocyte along with increasing in the production of insulin like
growth factor-1(IGF-1) and low in insulin like growth factor-binding protein-3(IGFBP-3) that produce from mainly visceral
fat. Another chemical from fat cell; leptin and insulin also quite high in obese and diabetic patient; may be the cause of
tumorigenesis by itself.
In conclusion if you are overweight or obese definitely it will decrease your life expectancy especially
if you already have diabetes along with cardiovascular complications for at least 10 to 15 years. If you smoke along with
it the life probably will be even shorter, perhaps 20 years.
Note: Current life expectancy for average American is
75 years for men and 80 years for women.
SUMMARY
Fat cells or adipocytes once believed to be the
inert cells with the main functions are accumulating excessive energy in the form of fat or oil for the future use, protecting
the physical body by cushioning and warming our body from the cold weather. In 1994, the leptin; hormone that control our
appetite, first discovered from the fat cells, ever since more than 50 hormones and chemicals were found to produce by the
fat cells. These chemicals affect our health and life and decrease our life expectancy.
According to our human evolution during the past
quarter million years, In general, our bodies never get use to the excessive fat. We constantly are in the state of starvation
more than the state of feast. I believe strongly the diabetic genes are the survival genes that help our body convert energy
from food to storage fat easily and efficiently so we can survive the famine longer. Since the industry evolution in the late
1800 our food supply has been increased. We have been eating more food than our body need and been eating too much carbohydrate
that our body never get use to. The results are obesity and diabetes epidemic. Over 60 percents of population of civilized
countries are obese and diabetics are rising along with associate diseases that I call them as the diseases of civilization:
diabetes, obesity, coronary heart disease, cerebrovascular disease, cancer, arthritis, autoimmune diseases.
As far as I know, not too many physicians aware
of the significance of the fat cells, the grave consequences of excessive fat in our body. Here is the summary of the fat
cell story.
The fat cells or
adipocytes are derived from mesoderm mesenchymal cell layer called adipoblasts during the third week of life or at the human embryo Carnegie stage7. Adipoblasts then differentiate to be preadipocytes, adipocytes, mature adipocytes under the control from the
several hormones, chemicals, ligands. Once the adipocytes become matured adipocytes, they start accumulate fat droplets in
the form of triglyceride or triacylglycerol. They also starting excrete several hormones such as leptin that controlling our
food intake, appetite, satiety, adiponectin, the hormone that keeps us healthy. Some experts said the adipocytes size can
increase up to 10 times of normal size to accommodate the ever increase the excessive energy. Once the fat cells are enlarge
in size and start running out of space. They start produce many more chemicals in order to protect themselves and recruiting
more fat cells from mesenchymal cells. Those chemicals more or less will create the problem to our body directly or in directly.
For examples they start to recruit monocyte from the circulation to adipose tissue to form macrophage by produce the chemical
named MCSF (macrophage colony stimulating
factor).
The reason for this is once the fat cell is enlarge to the point, the cell membrane
break, the fat cell contents leak, especially the triglyceride. The macrophage cells then perform their duty by engulfed the
fat, the dead tissue. The macrophages as you know also produce a lot of chemicals that cause inflammatory cascade in our body.
Another word, excessive fat content fat cells are becoming the foreign bodies that need to get rid of.
Other reasons, once the fat cells are enlarged they produce excessive leptin (hyperlipidemia)
to the point that the receptors in the brain no longer response as usual (leptin resistance). So the people keep eating more.
The adiponectin production also decrease this will decrease insulin sensitivity that cause type two diabetes. Adiponectin
itself is also anti-inflammatory process. The large fat cell also produces other chemicals such as angitensinogen, angiotensin
II that cause high blood pressure. Interleukin alpha that cause inflammation. Beside once the fat cells are full, the body
is unable to produce new adipocytes fast enough to accommodate the process of conversion of circulatory glucose to fat are
slowdown that cause high blood sugar or diabetes. In turn the pancreas continues to produce of lot insulin (hyperinsulinemia)
which require for activation of lipoprotein lipase to work. To the point the pancreas exhausted and eventually dies prematurely
due to over work that will cause type two diabetes insulin dependent. The increasing of the fat tissue either by increasing
in the size and or the number of fat cells also create other medical problems such as cancer, impotency; fat cells produce
the enzyme adipose aromatase that convert circulatory androgen to estrogen that make estrogen dependent cancer cells to grow
faster and make us to have less sexual desire (impotence) due to low testosterone that require for sexual function. The fat
cell also contend another enzyme called 11beta-hydroxysteroid dehydrogenase-1 that converts circulating inactive
cortisone to active cortisol, the stress hormone that cause the unnecessary ageing.
Beside the problems with the size and the number of the fat cells that create the medical
entities as mentioned above. The fat cells distribution is very important factor. The subcutaneous fat actually, if in moderate
amount is not bad. The matter of fact if we are deficient of this fat compartment (subcutaneous fat cells) we can develop
diabetes a little easier; the studies showed the new born underweight babies will develop diabetes in adult life. People from
Asia, even though they are not over weight also develop diabetes easier than Caucasians due to less subcutaneous fat cells
to accommodate extra fat that they eat than needed so the abdominal visceral fat which is more active metabolically increasing
in both size and numbers that again cause diabetes, hypertension, cardiovascular diseases, metabolic syndrome a lot sooner
than Caucasians. The fat distribution is dominantly control by the few hormones such as growth hormone, Insulin like growth
factor1, Estrogen, testosterone, stress hormones such as glucocorticoid and PPAR gamma agonist such as TZD(thiazolidinediones). During adolescence, the fat distribution will be more in the periphery or gluteal-hip region in female
due to the controlling of estrogen. In male due to the testosterone receptors located more in abdominal or central or visceral
region and less estrogen, the fat content will be more in this region (central). When the estrogen level in menopausal women
are low they will develop central adiposity same as men. As mention before the excessive of the stress hormone in certain
conditions such as Cushing syndrome and excessive stress from job will also cause central adiposity.
To me, the most important thing we learn from this research is once we eat more than
we need, will create the medical condition that I will call it “OVEREATING SYNDROME”.
-derangement of normal cellular homeostasis
-Mal-functions of natural hormones such as insulin, leptin, adiponectin
-Increase inflammatory process and the chemicals that require for the process
-Increase in fat distribution in non adipose tissue such as in the liver, pancreas.
The result is
-Decreasing life expectancy.
-Hyperlipidemia both hypertriglyceridemia and hypercholesterolemia
-Diabetes mellitus and complications
-Hypertension
-Atherosclerosis
-Cardiovascular diseases: coronary heart disease, peripheral vascular disease
-Cerebrovascular diseases: stroke, dementia
- Cancer
-Auto immune diseases
-Arthritis
The simple solution is eating the right amount
of food, eating the right kinds and balanced food. However, due to our eating traditions and habits, un-caring of the food
industry, lacking of knowledge of health care professionals, the ignorance of our government, this problem will continue.
For the first time in the last thousand years the human life expectancy is decline if we will not change or do something about
it.
Note: This subject will revise periodically.
April1, 2008
