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Regulation of metabolism in adipose tissue
ةينهدلا ةجسنلأا يف يئاذغلا ليثمتلا ةيلمع ميظنت
Dr. Othman Baothman
Metabolic regulation (BIOC 315)
Part2
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Introduction
• Mammals have two types of adipose tissue: White fat: the storage and release of lipid as fuel reserve.
• Brown fat: used to generate heat. Contain many more
mitochondria than white fat, and this is what gives it its colours.
• Stored lipid is oxidised in the tissue itself and the mitochondria can be uncoupled so that the oxidation generates heat.
• Brown fat is important in the newborn and in hibernating mammals.
• In white fat is stored as one droplet that typically almost fills the cell (see figure..). In function, the similarity is that both types of cell store triacylglycerol and may release fatty acids.
• The difference is that brown fat cells have a much higher oxidative capacity and may oxidize a large proportion of the fatty acids released from storage.
• In a 70 kg man, adipose tissue weighs approximately 14 kg, or
about half as much as the total muscle mass. In obese individuals
adipose tissue can constitute up to 70% of body weight.
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Colorized transmission electron
micrograph of adipocytes.
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x
• Sound like a clear-cut good fat/bad fat situation? Think again: new research suggests that “bad” white fatty tissue has a trick up its sleeve. Not only does it respond to cold, it can DIRECTLY sense cold temperature without relying on nerves.
• Huh? How can fatty tissues sense temperature?
• Let’s backtrack and talk about how brown fat works first. Imagine you’re jumping into the frozen arctic ocean (brrr). The terrible cold almost instantaneously activates sensory nerves in your body. These nerves signal to the temperature control centre– the hypothalamus at the base of the brain – that heat is desperately needed. In response, the hypothalamus releases norepinephrine, the major
neurotransmitter in the fight-or-flight sympathetic nervous system. This mobilizes a protein
calledUCP1that is present in brown fatty tissue, which triggers it to release its energy stores. Here, activation of the hypothalamus and sympathetic nervous system is absolutely necessary – mice bred without norepinephrine receptors are unable to mount this fat burning response.
• Or so it seems. Scientists took these norepinephrine receptor(beta-receptors) lacking mice and exposed them to a chilly 10 Celsius (50 F) for 20hrs. In normal mice, this activated thermogenesis-related genes in two populations of fat: between-shoulder brown fat and subcutaneous (under the skin) fat.
Unsurprisingly, in beta-receptor lacking mice, the brown fat response was almost completely obliterated, since they aren’t getting the trigger signal. However, subcutaneous fat more-or-less retained their ability to respond to cold, evidenced by robust thermogenic gene activation. Intriguingly, visceral fat (fat deep in the abdomen surrounding organs) did not respond to cold at all, in both normal and mutant mice. Since one major difference between these two populations of fat is that subcutaneous fat is closer to the surface of the body, scientists wondered if some types of cells in subcutaneous fat can “feel” and respond to cold autonomously, without the need for nerve activation.
• So what are these cells? Scientists took lab grown white and brown fat cells and directly cooled them down. For good measure, they also included beige cells – white fat cells that behave somewhat like brown fat – in the study.
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Rat fat cells secretes a number of hormones, such as insulin, adrenaline, glucagon,
prostaglandin …etc
لثم ،تانومرهلا نم ددع زرفت نارئفلا يف ةينهدلا ايلاخلا دنلاغاتسوربلا ،نوجاكولجلا ،نيلانيردلأا ،نيلوسنلاا ني
..
خلا
• Fatty acid biosynthesis
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Carbohydrates metabolism in adipose
tissue in fed state
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لكش 2.2
(TAG)
1. Increased glucose transport:
2. Increased glycolysis:
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لكش 2.3
In adipose tissue, glycolysis serves a synthetic function by supplying
glycerol
phosphate for triacylglycerol (TAG) synthesis (see figure 2.3).
TAG
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3. Increased activity in the HMP
• The major supplier of NADPH for fatty acid
synthesis. Two NADPH are produced for each
molecule of glucose that enters this pathway
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Fat metabolism in adipose tissue in
fed state
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1. Increased synthesis of fatty acids: Synthesis of fatty acids from acetyl CoA in adipose tissue is nearly undetectable in humans, except when refeeding a previously fasted individual (see Figure 2.2, ④). Instead, most of the fatty acids added to the lipid stores of adipocytes are provided by dietary fat (in the form of chylomicrons), with a lesser amount is supplied by VLDL from the liver.
لكش
2.2
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2. Increased TAG synthesis:
After consumption of a lipid-containing meal,
hydrolysis of the TAG of chylomicrons (from the intestine) and VLDL (from the liver) provides
adipose tissue with fatty acids (see Figure 2.2, ⑤
). These exogenous fatty acids are released by the
action of lipoprotein lipase (LPL), an extracellular
enzyme attached to the capillary walls in many
tissues—particularly adipose and muscle.
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x
2.5 لكش
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• Because adipocytes lack glycerol kinase, glycerol 3-phosphate used in TAG synthesis
must come from the glycolysis. Thus, in the well
fed state, elevated levels of glucose and insulin
favor storage of TAG (see Figure 2.2, 6 ).
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2.6 لكش
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3. Decreased TAG degradation: Elevated insulin favors the dephosphorylated (inactive) state of hormone-sensitive lipase (HSL) (see figure 2.7).
TAG degradation is thus inhibited in the well-fed state.
• للحت ضافخنا : TAG
لا لضفت نيلوسنلاا عافترا ةلاح يف ةلاح
ةطشن ريغلا (
ةرفسفم ريغلا يا )
زيبيللا ميزنلأ (
ظنا لكشلا ر
و 2.7 .) 2.8
لا للحت نود لوحت يلاتلابو ةلاح يف TAG
ةديجلا ةيذغتلا
.
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Or (HSL)
2.7 لكش
ةيلاتلا ةحفصلا يف حرشلا رظنا •
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لكشل زجوم حرش 2.7
Overview of fatty acid and glucose metabolism in white adipose tissue.
• The body’s main store of chemical energy is in the form of triacylglycerol (TAG) in white adipose tissue. Fat storage is the process of deposition of TAG. Fat mobilization (or lipolysis) is the process of hydrolysis of the stored TAG to release non-esterified fatty acids into the plasma (bound to the carrier protein albumin), so that they can be taken up by other tissues.
• Abbreviations:
LPL, lipoprotein lipase; glycerol 3-P, glycerol 3-phosphate; VLDL, very-low- density lipoprotein. The major pathways and main sites of hormonal regulation are shown: a plus sign indicates stimulation, a minus sign inhibition. Dashed lines show multiple enzymatic steps
ةيثلاثلا نوهدلا ةروص يف نوكي ةيئايميكلا ةقاطلل يسيئرلا مسجلا نزخم (TAG)
ةينهدلا ةجسنلأا يف
ءاضيبلا . بسرت ةيلمع وه نوهدلا نيزخت ىمستو TAG
Lipogenesis
؛ امنيب نوهدلا كرحت
Lipolysis ( )
نزخم للحت ةيلمع يه ريغ ةينهد ضامحأك امزلابلا يف ررحتتل TAG
ةرتسأم ( طبترم
ة لدت )+( ةملاع . ىرخلأا ةجسنلأا لبق نم ذخؤت نأ نكمي ثيحب ، ) لقانلا نيموبللأا نيتوربب زيفحت ىلع
ةملاع ،لعافتلا (
- ) لعافتلا طيبثت ىلع لدت .
تاوطخلا ددعت ىلع ةعطقتملا طوطخلا نيبت ةيميزنلأا
.
LPL: Lipoprotein lipase, HSL: hormone-sensetive lipase.
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Intertissue
relationships in the
absorptive state
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Carbohydrates metabolism of
adipose tissue in fasting
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Glucose transport into the adipocyte and its
subsequent metabolism are depressed due to low levels of circulating insulin. This leads to a decrease in fatty acid and TAG synthesis.
نيلوسنلاا تايوتسم ضافخنا ببسي ثت متي مدلا يف
لقن طيب
طيبثت يلاتلابو ينهدلا جيسنلا لخاد يف زوكولجلا ليثمتلا
ضامحلأا عينصت يف ضافخنا ىلإ يدؤي اذهو يئاذغلا
ةيثلاثلا نوهدلا و ةينهدلا
. TAG
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Fat metabolism of
adipose tissue in fasting
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1. Increased degradation of TAG: The activation of hormone-sensitive lipase (HSL) and subsequent
hydrolysis of stored TAG are enhanced by increasing of epinephrine and norepinephrine hormones. These hormones, which are released from the sympathetic nerve endings in adipose tissue, are physiologically important activators of hormone-sensitive lipase (HSL) (Figure 2.9, ①). [Note: Glucagon also activates the lipase].
• نومرهلل ساسحلا زابيللا ميزنا طيشنت نإ للحت مث نمو HSL
نزخملا TAG
نيرفنبلإاو نيلانيردلأا ةدايز قيرط نع زفحي .
يتلاو ،تانومرهلا هذه زرفت مت
سف تاطشنم يه ،ةينهدلا ةجسنلأا يف ةيفطاعلا ةيبصعلا تاياهنلا نم ةيجولوي
نومرهلل ةساسحلا زابيللا ميزنلإ ةمهم HSL (
)
( لكشلا رظنا و 2.9
، 2.7 ) ①
. م ده طيبثتو زيفحت رظنا ( زابيللا نوجاكولجلا اضيأ طشني : ةظحلام [ نيجوكيلاجلا لكش
9
].)
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• Hormonal regulation of triacylglycerol (TAG) degradation in the
adipocyte during fasting.
نوهدلا مدهل ينومرهلا ميظنتلا ةيمحشلا ةيلخلا يف ةيثلاثلا للاخ
مايصلا .
2.8 لكش
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Major metabolic pathways in adipose tissue during starvation
ةعاجملا للاخ ةينهدلا ةجسنلأا يف ىربكلا ةيضيلأا تاراسملا
2.9 لكش
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لكشلل زجوم حرش 2.8
ةيثلاثلا نوهدلا مدهل ينومرهلا ميظنتلا ةيمحشلا ةيلخلا يف TAG
Activation of hormone-sensitive lipase (HSL): This enzyme is activated when phosphorylated by a 3',5'-cyclic AMP(cAMP)–dependent protein kinase.
3',5'-Cyclic AMP is produced in the adipocyte when one of several hormones (such as epinephrine or glucagon) binds to receptors on the cell membrane, and activates adenylyl cyclase (Figure 16.15). The process is similar to that of the activation of glycogen phosphorylase. [Note:
Because acetyl CoA carboxylase is inhibited by hormone-directed phosphorylation when the cAMP-mediated cascade is activated (see Figure 2.8), fatty acid synthesis is turned off when TAG degradation is turned on.] In the presence of high plasma levels of insulin and glucose, HSL is dephosphorylated, and becomes inactive.
نومرهلل ساسحلا زابيللا ميزنأ طيشنت (HSL)
: لبق نمرفسفي امدنع ميزنلاا اذه طيشنت متي
AMP AMP جاتنا متي . زانيك نيتورب ميزنا ىلع دمتعملا يقلحلا بترت امدنع ةيمحشلا ةيلخلا يف يقلحلا
ط امم ةيلخل ا ءاشغ ىلع اهتلابقتسمب ) نوجاكولجلا وأ نيرفنبلإا لثم ( نيلانيردلاا تانوموره دحأ ةقلحملا ليلينيدأ ميزنا طشنت (adenylyl cyclase )
( لكشلا .) 2.8
طيشنتل ةلثامم ةيلمعلا هذهو
ًاقباس تسرد يتلاو زلايروفسف نيجوكيلجلا (
لكش رظنا 7
لولأا ءزجلا يف .)
تايوتسم دوجو يف
ميزنا نإف ،زوكولجلاو نيلوسنلأا امزلاب نم ةيلاع ةرفسفلا هنم لازت HSL
ًلاطعم حبصيو
.
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2. Increased release of fatty acids: Fatty acids obtained from hydrolysis of stored TAG are released into the blood (see Figure 2.9, ②). Bound to albumin, they are transported to a variety of tissues for use as fuel. The glycerol produced following TAG degradation is used as a gluconeogenic
precursor by the liver. [Note: Fatty acids are also converted to acetyl CoA, which can enter the TCA cycle, thus
producing energy for the adipocyte.].
للحت نم اهيلع لوصحلا مت يتلا ةينهدلا ضامحلأا قلاطإ متي مدلا يف TAG
( رظنا
لكشلا ) 2.7
و ( لكش 2.9 ، .) ② ةينهدلا ضامحلأا طبترت نيمويبللأاب
يح ،
ث مده نم جتنملا لورسلجلا . دوقوك اهمادختسلإ ىرخلأا ةجسنلأا ىلإ اهلقن متي زوكولج ردصمك مدختسي TAG gluconeogenic
دبكلا قيرط نع [ .
ةظحلام
: لخدت نأ نكمي يتلاو ، acetyl CoA ىلإ اضيأ ةينهدلا ضامحلأا ليوحت متي ةرود
، TCA
ةيمحشلا ةيلخلل ةقاطلا جاتنإ يلاتلابو
.].
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3. Decreased uptake of fatty acids: In fasting, lipoprotein lipase
activity of adipose tissue is low. Consequently, circulating TAG of lipoproteins is not available for TAG synthesis in adipose tissue.
يف زنا ةيطاشن نإف ،مايصلا ةلاح مي يف ) LPL ( زابيل نيتوربوبيلالا ضفخني ةينهدلا ةجسنلأا ثلاثلا نوهدلا نإف ،يلاتلابو . ةي
ف ةينهدلا تانيتوربلا نم TAG
ي ةرفوتم ريغ ةيومدلا ةرودلا عينصتل ةجسنلأا يف TAG
ةينهدلا
.
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Intertissue
relationships during
starvation
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Key map for feed/fast
cycle
