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.M.D., Ph.Dאסף רודיך המחלקה לביוכימיה קלינית והמרכז לתזונה
הפקולטה למדעי הבריאות
אונ' בן-גוריון
מאזן האנרגיה וההוצאה האנרגטית מאזן האנרגיה וההוצאה האנרגטית - הבסיס לטיפול בשינויי אורח חיים- הבסיס לטיפול בשינויי אורח חיים
)פרקים נבחרים...()פרקים נבחרים...(
בקרת משקל הגוף: פשוט מאוד....
מטרות:אם זה כ"כ פשוט, למה זה בעצם כ"כ מסובך?1.
מנגנונים בסיסיים בבקרת צריכת האנרגייה )אכילה(2.
מנגנונים בסיסיים בבקרת ההוצאה האנרגטית3.
דוגמאות ליחסי הגומלין המורכבים בין הצריכה 4.
האנרגטית וההוצאה האנרגטית
איך סוכרת מסבכת עוד את העניינים...5.
זה מסובך!
Simple: The energy balance and the laws of
thermodynamicsEnergy expenditure
Energy intake
The energy balance:
Energy expenditure
- Involuntary:- BMR (basal metabolic rate)
- TEF (Thermic effect of food)
- Voluntary (activity):- NEAT (non-exercise activity thermogenesis)
- ET (exercise thermogenesis)
Energy intake
Food intake (calories):Nutrients:
lipidsCarbohydratesproteins
The control of food intake
- Complex process: Metabolic, Neuro-endocrine, Mental (including mood), Social, Cultural factors
- Complex afferent signals (orexigenic Vs anorexigenic):- hunger versus satiety (feeding frequency);
- “fullness” signals (meal size);
- energy abundance signals (short/long term);
- food composition signals (olfaction);
- Mood, social, cultural
- Mediators:- Neuronal:
- Central: Hypothalamus, brain stem, Area Postrema, “reward” centers, Cortical centers
- peripheral: Vagus
- Hormonal (pancreas, fat tissue, GI)
Hypothalamus
= anorexigenicorexigenic =
The Arcuate Nucleus of the Hypothalamus: integrator of orexigenic
and anorexigenic signals
food-seeking behaviour
NPY(Orexogenic
signal)
αMSH(Anorexogenic
signal)**
**
** MC-R4(melanocortin Receptor 4)
Summary: GI, pancreatic and adipose signals for hypothalmic regulation of food
intake
food-seeking behaviour
NPY(Orexogenic
signal)
αMSH(Anorexogenic signal)
Adipose tissue
Hypothalamus
= anorexigenicorexigenic =
(Nature 404: 661,
2000)
leptin
Adipostatic action of Leptin:Leptin signals fat-storage
sufficiency
(Science 304:63-4, 2004)
food-seeking behaviour
NPY (Orexogenic
signal)
αMSH(Anorexogenic
signal)
-
-
+
+
Leptin effect in the arcuate nucleus of the hypothalamus: 1.
Direct (rapid) effect 2 .Neuroplasticity (h)
Excitatory
synapses
+-
+
Inhibitory
synapses
-
3 .Developmental
Adipose tissue
Hypothalamus
GI tract
Pancreas
= anorexigenicorexigenic =
- Does insulin resistance develop in the brain?
- Does it mediate reduced anorexigneic signal?
- Can common mechanisms underlie insulin and leptin resistance???
The energy balance:
Energy expenditure
- Involuntary:- BMR (basal metabolic rate)
- TEF (Thermic Effect of Food)
- DIT (Diet-Induced Thermogenesis)
- Voluntary:- NEAT (non-exercise activity thermogenesis)
- ET (exercise thermogenesis)
Energy intake
Food intake (calories):Nutrients:
lipidsCarbohydratesproteins
Obligatory Vs. Facultative (adaptive)
Components of Total Daily Energy Expenditure (TDEE)
Exercise thermogenesis
Facultative )adaptive( thermogenesis
Obligatory thermogenesis
- Essential thermo.
- Endothermic thermo.
Diet-induced thermogenesis
Muscle
Brown Adipose Tissue
White Adipose Tissue
GI, liver, WAT, muscle
BAT, WAT? Muscle?
All organs
Most organs
Acetylcholine )central(
Norepinephrin )central(
Thyroid hormone
Insulin
Norepinephrin )central(
none
Thyroid hormone
30%)20 to >100(
~ 60%
6-12 %
: גילגול אנרגייה האגורה ההוצאה האנרגטית
, והאנרגייה ATPבמזון )"שריפת" המזון( לייצור
ל"עבודה" ATPהאגורה ב-
מיטוכונדריה!!
"שריפת המזון" ATP ייצור ATP ניצול
חומר מחזר
פוטנציאל אלקטרו-כימי
נוראדרנלין והורמון הטירואיד מבקרים את המספר והיעילות האנרגטית של מיטוכונדריות
NRF – nuclear respiratory factor
mtTF-A – mitochondrial trascription factor A
PGC-1 – PPARγ co-activator 1
CREB – cAMP responsive element binding protein
DII – Thyroxine 5’-deiodinase type 2
mtTF-A
Noradrenalin
Thyroid hormone
mitochondria
The energy balance
Energy expenditure
Energy intake
צריכת האנרגייה מבקרת את ההוצאה האנרגטית
השפעת הצריכה האנרגטית על ההוצאה עדות לעצמת מנגנוני הבקרה של מאזן האנרגייההאנרגטית:
Energy intake and energy expenditure exhibit complex
inter-relationsEnergy expenditure
Energy intake
Food intake (calories):Nutrients:
lipidsCarbohydratesproteins
Processes:Eating initiation
(frequency)Satiety sensation /
appetite regulation (meal size)
Diet composition
- Involuntary:- BMR (basal metabolic rate)
- TEF (Thermic effect of food)
- Voluntary (activity):- NEAT (non-exercise activity thermogenesis)
- ET (exercise thermogenesis)
Body mass
צריכת בקרת ההוצאה האנרגטית ע"י: משקל הגוף בכל-זאת איננה מלאה האנרגייה
משתנה
~60% decrease
~20%
הבדלים בין-אישיים במידת ההשפעה של תרומת צריכת אנרגייה על הוצאת האנרגייה:
הגנטיקה
- identical, severe caloric deficit in 14 female monozygotic twins:
- weight loss of 5.9 – 12.4 Kg
- High correlation in the change within twin pairs (r=0.88), but much less between pairs
(Int J Obes 25: 533, 2001)
- a 1000 kCal over-eating in 12 male monozygotic twins for 100 days:
- weight gain of 4.3 – 13.3 Kg
- within twin pairs variability 6-fold lower than between pairs variability
(NEJM 322: 1477, 1990)
Genetics plays an important role in
the association between Energy intake and Energy expenditure :
The ability to regulate the coupling of
food intake, ATP production, and ATP utilization
Nutrient combustion results in fixes amount of reducing equivalent
Entering reducing equivalent into the Mt through the glycerol phosphate shuttle versus aspartate-malate shuttle
Fixed amount of ATP is produced for a certain amount of protons pumped out of the Mt
Uncoupling proteins
The coupling, uncoupling, and futile cycling of reactions in energy
metabolism:
Fuel combustionATP synthesis ATP utilization for work
חומר מחזר
פוטנציאל אלקטרו-כימי
Coupling the electron transport chain to ATP
synthesisNADH + H+ + ½O2 NAD+ + H2O G = -52.7 kCal/mol
3ADP +3Pi 3ATP G = 21.9 kCal/mol
(oxidation)
(phosphorylation)
The coupling, uncoupling, and futile cycling of reactions in energy
metabolism
Nutrient combustion results in fixes amount of reducing equivalent
Entering reducing equivalent into the Mt through the glycerol phosphate shuttle versus aspartate-malate shuttle
Fixed amount of ATP is produced for a certain amount of protons pumped out of the Mt
Uncoupling proteins
Fixed amount of ATP is required for fixed amount of biological activity
- Futile cycles
- higher Vs lower efficiency isoforms
ה"נטייה להשמנה" תלוייה במידת הצימוד וביכולת להפר את הצימוד שבין ייצור
ATP וניצול ATPאנרגייה מהמזון, ייצור
Food
Energy
ATP
+ADP +Pi
+ADP +Pi + WORK
Synthesis
Ion transport
Muscle work
Energy expenditure
Energy intake של גדולההשפעה EI על EE:
בין גדולהיכולת הפרת צימוד ייצור אנרגייה לעבודה
:EE על EI של קטנההשפעה
בין קטנהיכולת הפרת צימוד ייצור אנרגייה לעבודה
משמעויות טיפוליות – לא פרמקולוגיEnergy expenditure
Energy intake
-Increasing Exercise:- direct increase in TEE- indirect, EXTENDED increase in TEE through elevation in BMR (Thyroid, Sympathetic - UCP)
- prevents the adaptive decrease in BMR during caloric restriction
-Increasing NEAT:- life style choices- work environment engineering- cultural change
-Increasing DIT:- Low quality protein?
- Food composition choices:
- High protein? Low carb? (Increase satiety?)
- Decreasing energy extraction from food – dairy products?
- Decrease highly calorie-dense foods
- Decrease soft drinks- GI microbial flora:- Decreasing energy extraction from food (Nature 444: 1027, 2006)
משמעויות טיפוליות – פרמקולוגיהEnergy expenditure
Energy intake
- Increasing anorexigenic, decreasing orexigenic signals:
- GLP1 analogues (Extenetide) and DPP4 inhibitors (Citagliptin)
- Metformin - Ghrelin- Decreasing reward signals to food:
- CB1 inhibitors (Rimonabant)
- Decreasing nutrient absorption:
- Pancreatic lipase (Orlistat)
- A glucosidase inhibitors (Orlistat)
- Increasing BMR, non-voluntary components of NEAT
- beta 3 adrenergic agonists
ומה בסוכרת?Energy expenditure
Energy intake
-Increasing Exercise:- direct increase in TEE- indirect, EXTENDED increase in TEE through elevation in BMR (Thyroid, Sympathetic - UCP)
- prevents the adaptive decrease in BMR during caloric restriction
-Increasing NEAT:- life style choices- work environment engineering- cultural change
-Increasing DIT:- Low quality protein?
- Food composition choices:
- High protein? Low carb? (Increase satiety?)
- Decreasing energy extraction from food – dairy products?
- Decrease highly calorie-dense foods
- Decrease soft drinksDelayed increase in insulin sensitivity (risk of hypo up to 72 h from exercise)
Diabetics may be particularly resistant to weight loss by caloric restriction
Diabetics seem to have increased BMR compared to weight-matched non-diabetics: increase GNG? Direct effect of hyperglycemia?
Glucosuria – abnormal loss of calories
Kibbutz Ruhama, Israel
(photo: Zvia Rudich)
