Energy flow in the organism

Transcription

1 I. Parameters of energy metabolism, basal metabolic rate, measurements. II. Control of food intake, hunger and satiety Péter Sántha, Energy flow in the organism NUTRIENTS PHYSICAL WORK HEAT PRODUCTION BREAKDOWN (CATABOLISM) ATP SYNTHESIS (ANABOLISM) WASTE PRODUCTS BODY COMPOSITION STORAGE SUBSTANCES 1

2 PHYSICAL PARAMETERS FOR MEASUREMENT OF THE ENERGY UPTAKE/EXPENDITURE ENERGY (Joule) RATE OF ENERGY CONVERSION (Watt) = TIME (sec) 1kJ = 1000 Ws = 0,24 Kcal (1 Kcal ~ 4 kj) EXTERNAL WORK EFFICIENCY (η)% = 100 ENERGY USED Efficiency of the whole body (mechanical work) max. 20 % Efficiency of the heart activity: 15-40%!! Metabolic rates of the whole body Basal (BMR), Total (TMR) and Resting (RMR) Metabolic Rates Resting Metabolic Rate: metabolic rate of a resting (physical, mental) organism Total Metabolic Rate: RMR + activity-induced metabolic rate increase Basal Metabolic Rate: metabolic rate determined under standard conditions 6500 kj/day (75 W) kj/day (100 W) Conditions to measure BMR: 1. Morning 2. Physical and mental rest (lying position) 3. Fasting (12 hours after the last meal) 4. Indifferent ambient temperature, normal core temperature 2

3 Which factors can influence the metabolic rate? Biological (e.g.: cyrcadian) rythms: Neuro-humoral (hormonal) regulation (e.g.: Hypothalamo-hypophyseo-adrenal system: ACTH; corticosteroids) Sleep-wake cycle hour Which factors might influence the metabolic rate? 2. Muscle activity: muscle tone and contractions (In rest: muscle: 25% of RMR; liver 26%, brain 18%, heart 17 %, kidney 9%) 3. Food intake: - postprandial metabolic rate increase (ca. 6%) SDA: Specific Dynamic Action of protein protein rich food transiently increases the MR by up to 30% 4. Ambient- and body (core) temperature Thermoregulation heat production (thermogenesis) Van t Hoff rule: the rate of chemical reactions increases by factors 2-4x upon every 10 C increase in the temperature 3

4 Dependency of heat production on the ambient temperature and on the thermogenetic processes Influence of sex, age and body dimensions (surface area) on the basal metabolic rate BMR AGE 4

5 Energy expenditure during different levels of physical activity Sleeping Awake lying still Sitting at rest Standing relaxed Light exercise Swimming 280 KJ/h 320 KJ/h 400 KJ/h 420 KJ/h 800 KJ/h 2000 KJ/h Running (10 km/h) 2300 KJ/h (~55 g fat) Walking up stairs 4400 KJ/h (~120 g fat) Resting condition Arithmetic task Shortly after finishing the task 1 minute after finishing the task EMG recording during the execution of an arithmetic task (mental activity) 5

6 MEASUREMENT OF METABOLIC RATE CxHyOz + no2 x CO2 + h H2O + energy Measurement of the energy content of the consumed food: difficulties: efficiency of the energy utilization, storage, energy of the waste products Measurement of the liberated energy: Direct method - direct calorimetry measurement of the heat production of the body Indirect method measurement of the oxygen utilization direct calorimetry to measure the total quantity of heat production E = Q 6

7 indirect calorimetry measurement of oxygen utilization C x H y O z + no 2 x CO 2 + h H 2 O + Energy Metabolator (modified spirometer): Clamp T-valve oxygene O 2 Util =dv/dt Soda lime Ergospirometry 7

8 C x H y O z + no 2 x CO 2 + h H 2 O + Energy (biologic) energy content: liberated energy after oxydation of unit quantity of nutrient Nutrients: fats proteins carbohydr. glucose ethanol Energy- (caloric) equivalent: liberated energy after oxydation with 1 l O 2 released consumpted carbohydrates fats proteins Relationship between RQ and the composition of the food Oxydation of glucose: C 6 H 12 O O 2 => 6 CO H 2 O kj RQ = 1; EE = 20,2 kj / l O 2 Oxydation of fat (tripalmitoil-glycerate) C 57 H 110 O ,5 O 2 => 57 CO H 2 O kj RQ = 0,7; EE = 19,6 kj/ l O 2 Mixed food: 15% protein - 60 % carbohydrate - 25% fat: RQ = 0,82; EE = 20,2 kj/ l O 2 8

9 relationship between the respiratory quotient and the energy equivalent protein breakdown is relatively constant (15% of MR) Important is the carbohydrate/fat ratio: Example for the calculation of metabolic rate: O 2consumed.=280 ml/min RQ=0,82 E/ t=0,28 l/min x 20,2 kj/l=5,66 kj/min (94 W) Variability of the RQ: Hyperventilation (RQ ) removal of CO 2 from the lung (FRC!) released consumed Foie gras Increased: Hunger (Diabetes mellitus) - - mobilization of fat depots + gluconeogenesis- RQ decreased: - Force-feeding (fattening) of goose - RQ 9

10 Diagnostic value of the BMR: Exercise physiology - sport medicine Detection of the onset and severity of circulatory shock Post-aggression increase of the metabolic rate (Steroid hormones) Diseases of the thyroid gland (T3/T4 hormone production) Control of food intake Short term regulation: hunger - satiety Long term regulation: body weight hunger satiety Interdigestive phase Food intake Digestive phase 10

11 Control of food intake, hunger and satiety Hunger: sensation caused by the need to eat food (motivation state) interdigestive phase Satiety: absence of hunger feeling full digestive phase Appetite: sensation during eating selection of food (desire) Emerging mechanisms to control hunger and satiety: Glucostat theory: constancy of blood glucose level peripheral and central glucose sensors (nutrient sensing) Gastrointestinal hormones hypothalamus (e.g.: CCK - n.x.) Neural signals: e.g.: stretch receptors (stomach) hypothalamus Long term regulation (stored energy): endocrine functions of hormones produced by the adipocytes (fatty tissue) e.g. Leptin (leptos thin) signals quantity of depot fat Stereotaxic experiments functional mapping of the deep regions of the brain - hypothalamus Walter Rudolph HESS (N.P.: 1949) Observations on the role of hypothalamus to control autonomic functions 11

12 Stereotaxic Neurosurgery Deep Brain Stimulation 12

13 Ventromedial nuclei: satiety center (ablation: hyperphagia) Lateral area: hunger center (ablation: aphagia, starvation) Actions of transmitters applied locally to the hypothalamic areas ANOREXIGENIC (inhibitory) OREXIGENIC (stimulatory) (orexos Appetite, Hunger) POMC: Pro-Opio-Melano-Cortin) Alpha-MSH CART: Cocaine- and Amphetamine-Regulated Transcript Cholecystokinin GLP-1 (Glucagon-Like Peptide) (fibres originating from the medulla) Neuropeptide Y (NPY) AGRP: Aguti-Related Peptide Gamma-aminobutyric acid (GABA) Galanin (GAL) Norepinephrine (NE) Endogenous opioid peptides (EOP) Modified from Kalra SP, Dube MG, Pu S, et al: Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 20:68-100,

14 Current hypothesis: reciprocal actions of orexigenic and anorexigenic neuron populations (arcuate nucleus) 2nd order neurons 1st order neurons Efferent connections of the central hypothalamic neurons 14

15 Peripheral signals Chemical senses: oral mucosa - taste receptors GI tract: Absorbed metabolites (glucose, FFA, amino acids) GIT hormones: ghreline stimulates ingestive behaviour (feed forward) CCK, PYY (peptide Tyr-Tyr), GLP-1, Serotonine - mechanical distention -vagal afferents (glucose, peptides) Pancreas islet cells: insulin, amylin, glucagon Liver vagal afferents (glucose and GLP-1 sensitive) Adipose tissue: leptin, adiponectin (metabolic effects) Origins of the peripheral signals controlling the food uptake and eating behavior 15

16 Leptin receptor (OB-Rb) deficient mouse: obesity, hyperphagia, hypoactivity ob/ob mutant (leptin deficient) wild type Feed-back regulation to control the amount of stored fat and body weight Other adipokines: TNF-α, IL-6 (Insulin-resistance) Adiponectin (BMR ) 16

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