Άσκηση και Παχυσαρκία Μεταβολισμός, Ενεργειακό Ισοζύγιο και Υποδόριος ιστός στην Παχυσαρκία Σακκάς Γεώργιος PhD Τμήμα Επιστήμης Φυσικής Αγωγής και Αθλητισμού ΠΑΝΕΠΙΣΤΗΜΙΟ ΘΕΣΣΑΛΙΑΣ

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. 2

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. 3

Σκοποί ενότητας Η αναγνώριση της σημαντικότητας του υποδόριου ιστού ως λειτουργικού οργάνου και η σημασία του στην υγεία και τον μεταβολισμό του ανθρώπου 4

Περιεχόμενα ενότητας 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 5

What is the Adipose Tissue? Is a complex organ that regulates and coordinates energy homeostasis Composed of – Adipocytes – Fibroblasts and fibroblastic pre- adipocytic cells – Endothelial cells – Nerves – Immune cells 6

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 7

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 8

Brown Adipose Tissue 9 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)

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 10 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) 11 Energy Balance in Obesity

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/m 2 need to gain 25kg in order to became obese with BMI 30kg/m 2, meaning 19kg of fat and 6kg of muscle (Lissner et al, 1991) 12

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 13

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) 14

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) 15

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 16

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 ?)… 17

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 18

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) 19

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) 20

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 21

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 22

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) 23

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 mg/dL (normal range: mg/dL) Steatotic liver and diabetes (Considine et al, 1996, Oral et al, 2002) 24

Lipoatrophy 25

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) 26

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 27

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 etc 28

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 29

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 30

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) 31

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 32

Τέλος Ενότητας ΠΑΝΕΠΙΣΤΗΜΙΟ ΘΕΣΣΑΛΙΑΣ