ΠΑΝΕΠΙΣΤΗΜΙΟ ΘΕΣΣΑΛΙΑΣ
Άσκηση και Παχυσαρκία
Μεταβολισμός, Ενεργειακό Ισοζύγιο και
Υποδόριος ιστός στην Παχυσαρκία
Σακκάς Γεώργιος PhD
Τμήμα Επιστήμης Φυσικής Αγωγής και Αθλητισμού
Άδειες Χρήσης
• Το παρόν εκπαιδευτικό υλικό υπόκειται σε άδειες
χρήσης Creative Commons.
• Για εκπαιδευτικό υλικό, όπως εικόνες, που υπόκειται
σε άλλου τύπου άδειας χρήσης, η άδεια χρήσης
αναφέρεται ρητώς.
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Χρηματοδότηση
• Το παρόν εκπαιδευτικό υλικό έχει αναπτυχθεί στα πλαίσια
του εκπαιδευτικού έργου του διδάσκοντα.
• Το έργο «Ανοικτά Ακαδημαϊκά Μαθήματα Πανεπιστημίου
Θεσσαλίας» έχει χρηματοδοτήσει μόνο τη αναδιαμόρφωση
του εκπαιδευτικού υλικού.
• Το έργο υλοποιείται στο πλαίσιο του Επιχειρησιακού
Προγράμματος «Εκπαίδευση και Δια Βίου Μάθηση» και
συγχρηματοδοτείται από την Ευρωπαϊκή Ένωση (Ευρωπαϊκό
Κοινωνικό Ταμείο) και από εθνικούς πόρους.
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Σκοποί ενότητας
• Η αναγνώριση της σημαντικότητας του
υποδόριου ιστού ως λειτουργικού οργάνου και
η σημασία του στην υγεία και τον μεταβολισμό
του ανθρώπου
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Περιεχόμενα ενότητας
•
•
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•
•
•
•
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What is Adipose Tissue
Energy Balance in Obesity
Metabolic Changes in Weight Gain & Loss
Susceptibility to Weight Gain (relapse)
Importance of Adipose Tissue
Adiponectin & Leptin
What happens when we get fatter
Inflammation and Obesity
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What is the Adipose Tissue?
• Is a complex organ that regulates
and coordinates energy
homeostasis
• Composed of
– Adipocytes
– Fibroblasts and fibroblastic preadipocytic cells
– Endothelial cells
– Nerves
– Immune cells
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What is the Adipose Tissue?
• Originally thought to just be an energy storage
• It is an organ
• Composed of White Adipose Tissue (WAT) and Brown
Adipose Tissue (BAT)
• Both types of cells differentiates form mesenchymal
stem cells (μεσεγχυματικά κύτταρα) - Adipogenesis
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White Adipose Tissue
• It is the main type of adipose tissue
and can be found in subcutaneous
regions, surrounding visceral
organs and in the face
• Contains large unilocular lipid
droplets
• Differs between subcutaneous and
visceral
• It is an active endocrine organ that
regulates
– Insulin sensitivity, lipid metabolism
and satiety
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Brown Adipose Tissue
• Mainly participates in Thermogenesis
• Located in discrete pockets in the
paravertebral (παρασπονδυλικός),
supraclavicular (υπερκλείδιος) and
periadrenal (επινεφρίδια) regions
• Histologically distinct from WAT
• Multiloculated adipocytes
• Large number of mitochondria (brown
colour)
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Energy Balance in Obesity
• Why am I obese?
-Because of my Genes?
-Because of my Metabolism?
Or
-Because of the environment, food intake and
lack of physical activity?
Some individuals gain weight much easier than others
or keep off weight after a successful diet
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Energy Balance in Obesity
• Environmental changes influence energy
balance (increase energy intake and
decrease physical activity)
• 77% of the weight gain is due to Low
Activity Energy Expenditure
(French et al, 2001) (Weinsier et al, 2002)
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Is our body weight well regulated?
• Lack of regulatory process of body weight
– Weight does not vary over short time period
– But in a 18yr study body weight fluctuated 10kg
• An increase in food intake of 800kj/d (2 soft drinks/day) will
increase body weight by 25 kg in 2.5yr
• From the gained weight, the 75% is fat & the 25% is muscle
• For example: 70kg with BMI of 22 kg/m2 need to gain 25kg
in order to became obese with BMI 30kg/m2, meaning 19kg
of fat and 6kg of muscle
(Lissner et al, 1991)
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Stability of body weight
…is achieved by
• Controlling food intake
• Resting energy expenditure
• Physical activity
Obesity develops when one or more of these
factors are ineffective
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Metabolic Changes in Weight Loss
• During diet (reduction in energy
intake):
– dietary-induced thermogenesis falls
10%
– metabolic rate is decreased by 5-8%
For example: for a reduction of body
weight from 100kg to 70kg (30kg
weight loss) a 15% reduction in energy
requirements is expected for weight
maintenance (from 1800Kcal/day to
1260 Kcal/day)
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Metabolic Changes in Weight Loss
•
•
•
•
Secondary changes in sympathetic nervous system activity
Leptin concentration falls
Leptin changes - related to REE and fat oxidation falls
Urinary Noradrenaline excretion falls
Relapse (υποτροπιασμός)
• The low fat oxidation rate and the low leptin levels seen in
POST-OBESE individuals predispose to weight relapse
•
(Rosenbaum et al. 2000) (Doucet et al. 2000) (Filozof et al. 2000)
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Metabolic Changes in Weight Gain
• Weight gain is associated with increases in
energy expenditure due to:
– dietary-induced thermogenesis
– metabolic cost due to
• Synthesis of glycogen
• Synthesis of protein
• Deposition of fat
• Digestion of food
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Variability in response to Weight Gain
Why some people, no matter how much food
they eat, don’t gain weight or at least as much
as others?
The answer is (not so sure yet ?)…
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Variability in response to Weight Gain
• Non-exercise activity thermogenesis
(fidgeting, spontaneous muscle
contraction and maintaining posture)
(Levine et al. 1999)
• Fidgeting or similar activities can
sufficiently balance increased energy
intake
• Different type of muscle fibers prefer
different type of substrate: type I like
fat, type II like sugar
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Susceptibility (επιρρέπεια - τάση) to weight gain
• In some individuals during weight loss
(underfeeding), energy expenditure falls
rapidly and in greater extend compared with
others
• This is a potential susceptibility factor to
weight gain in the future (Webber et al. 2003)
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Gene Mutation and Obesity
• All mutations are related to abnormalities in
energy intake rather than of energy expenditure
• Leptin mutation – early onset obesity due to
hyperphagia (Montague et al. 1997)
• Melanocortin-4 mutation (antagonist of satiety
signal – αίσθηση κορεσμού) – accounts for up to
5% of childhood morbid obesity (Barsh et al.
2000)
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Importance of Adipose Tissue
• Adipocytes are stores of free fatty acids
• Adipocytes are also endocrine organs with multiple metabolic roles
in regulating whole-body physiology (Greenberg & Obin 2006)
• οb/ob mice (no subcutaneous fat at all) have severe lipoatrophic
diabetes: insulin resistance, hyperglycemia, hyperlipidemia and
steatotic liver (Gavrilova et al. 2000)
• Transplantation of adipose tissue completely reversed the
characteristic phenotype
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Fat as an Endocrine Organ
• Adipose tissue secretes proteins called
“adipokines” that act in an autocrine
(αυτοκρινής ), paracrine (παρακρινής) or
endocrine fashion to control metabolism
• More than 50 adipokines have been identified
but LEPTIN & ADIPONECTIN have been well
studied
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Leptin – Λεπτίνη
• The first adipocyte hormone identified
• Secreted from the fat cells
• Influences food intake through a direct effect on the
hypothalamus
• Plasma leptin concentration is correlated with BMI
• Leptin concentration increases when we gain weight, in
order to increase REE and decrease food intake
•
(Greenberg and Obin 2006, Halaas et al, 1995)
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Leptin in obesity
• Leptin concentration is high due to increased fat cells
• However due to chronic effect of high leptin levels,
obese individuals are “Leptin Resistant”
• In humans with a rare disorder called lipoatrophy (little
or no fat), leptin levels are very low (hypoleptinimic)
• In these patients serum triglycerides are 2000-3000
mg/dL (normal range: 10-190 mg/dL)
• Steatotic liver and diabetes
•
(Considine et al, 1996, Oral et al, 2002)
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Lipoatrophy
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Adiponectin – Αντιπονεκτίνη
• Expressed in adipose tissue
• Enhances insulin sensitivity in muscles and liver
• Increases FFA oxidation
• Decreases serum FFA, glucose and Triglycerides (even after high fat
meal)
• Plasma Adiponectin falls with increasing obesity
• Low Adiponectin concentrations correlate with insulin resistance
and hyperinsulinemia
• Low Adiponectin increases the development of Atherosclerosis
•
(Yamauchi et al, 2001, Arita et al, 1999, Greenberg & Obin 2006)
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Adipocytes Action
• Both adiponectin and leptin reduce FFA and
Triglycerides due to increased fat oxidation
• The action is through the activation of the
AMPK enzyme that also promotes glucose
transport
• Exercise also activates AMPK - reduce FFA and
improves insulin sensitivity
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What happens when we get fatter
• Adipocytes are getting bigger
• Fasting FFA increases
• The increased FFA induce insulin
resistance
• More prone to diabetes
• Pro-inflammatory protein levels increase,
such as: TNF-a, interleukin-6, TFG-beta
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What happens when we get fatter
• Macrophages in fat cells increase
• Macrophages are responsible for most of the cytokine
production in obese adipose tissue
• Due to this inflammation, insulin levels are increased
• Inflammation is the protagonist for the obesity-related
complications
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Inflammation due to Obesity
• Cytokines reduce adiponectin expression
• Adiponectin is reduced in obesity
• Adiponectin protects the cell from TNF-a and
other cytokines that induce Atherosclerosis
• IL-6 is increased in obesity
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Inflammation due to Obesity
• IL-6 increases lipolysis and correlates with
Insulin Resistance in the liver
• Elevated IL-6 is a predictor of type II
diabetes and of myocardial infraction
• Cortisol enzymes are increased in obesity
inducing central adiposity
(Xu et al 2003, De pergola et al, 2002, Klover et al, 2003,
Greenberg & Obin 2006)
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Summary
• Fat cells are endocrine organs
• Small fat cells in lean individuals promote metabolic
homeostasis
• Large fat cells in obese individuals recruit macrophages
and promote inflammation and insulin resistance
• Leptin and Adiponectin promote fat oxidation and
glucose transport
• Obesity induces leptin resistance and decreases
adiponectin concentration affecting whole body
metabolism
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ΠΑΝΕΠΙΣΤΗΜΙΟ ΘΕΣΣΑΛΙΑΣ
Τέλος Ενότητας