Dietary Balances; Regulation of Feeding; Obesity and Starvation

1. Dietary Balances; Regulation of Feeding; Obesity and Starvation Prof. dr. ZoranValić Department of Physiology University of Split School of Medicine

2. Energy Intake and Output • used or stored for later use (fat) • appropriate balanced intake (proteins, carbohydrates, fats, minerals, and vitamins) • 1 g carbohydrates– 4.1 Cal(98% – 4(17 kJ) • 1 g fats– 9.3 Cal(95% –9 (38 kJ)) • 1 g proteins– 4.35kJ (92% –4 (17 kJ)) • 45%, 40%, 15% (average Americans)

4. 30-50 g of proteinper day (20-30 g are degraded) • partial proteins (inadequate quantities of certain essential amino acids) • protein of corn has almost no tryptophan • protein-deficiency syndrome – kwashiorkor • carbohydrates and fats – protein sparers

7. nitrogen excretion can be used to assess protein metabolism (16% nitrogen) • 90% of nitrogen is excreted in the urine (urea, uric acid, creatinine), 10% by feces • rate of protein breakdown(g) = N2(urine)x 1.1 x 6.25 (100/16) • negative or positive nitrogen balance

8. “respiratory quotient” – ratio of CO2 production to O2 utilization (1h and more) • fat utilization (0.7), carbohydrates (1.0), proteins (0.8) • excess hydrogen atoms • right after meal close to 1.0; 8-10 h after meal about 0.7; in diabetes melitus always about 0.7

9. Regulation of Food Intake and Energy Storage • only 27% of the energy ingested normally reaches the functional systems of the cells • food intake, energy expenditure and fat storage – environmental, cultural and genetic factors + physiological control • “epidemics” of obesity (64% & 33%) • 2000 Cal daily expenditure of energy (6000-7000 Cal)

10. Neural Centers Regulate Food Intake • sensation of hunger (rhythmical contractions of stomach and restlessness) • appetite –desire for particular type of food • feeling of satiety

12. lateral nuclei of the hypothalamus– feeding center (hyperphagia, inanition) • operates by exciting the motor drives to search for food • ventromedial nuclei of the hypothalamus – satiety center (aphagia, hyperphagia) • other centers also play a major role (arcuate!), hormonal secretion (thyroid and adrenal glands, pancreatic islet cells)

13. integration of neural signals from the gastrointestinal tract (stomach filling), chemical signals from nutrients in the blood, signals from gastrointestinal hormones, hormones released by adipose tissue and signals from the cerebral cortex (sight, smell, and taste) • feeding behavior • orexigenic and anorexigenic substances and receptors – therapeutic sites

16. Neurons and Neurotransmitters in the Hypothalamus • pro-opiomelanocortin(POMC) neurons • α-MSH (α-melanocyte-stimulating hormone) • CART (cocaineandamphetaminerelatedtranscript) • neurons that produce orexigenic substances • NPY (neuropeptideY) • AGRP (agouti-relatedprotein)

17. activation of POMC neurons decreases food intake and increases energy expenditure • activation ofNPY-AGRP neurons increases food intake and reduces energy expenditure • major targets for: leptin, insulin, cholecystokinin (CCK), and ghrelin

18. POMC neuronsreleaseα-MSH (acts on melanocortin receptors found especially in neurons of the paraventricular nuclei) • at least five subtypes of melanocortin receptors • MCR-3 and MCR-4 are especially important in regulating food intake and energy balance • activation of these receptors reduces food intake while increasing energy expenditure • inhibition has an opposite effect

19. MCR activation is mediated by activation of nucleus tractussolitarius (sympathetics) • defective signaling of the melanocortin pathway is associated with extreme obesity • mutations ofMCR-4 – most common known monogenic (single-gene) cause of human obesity (5-6% of early-onset severe obesity in children)

20. AGRP is a natural antagonist of MCR-3 and MCR-4 receptors • role of AGRP in normal physiologic control of food intake is unclear • excessive formation of AGRP in mice and humans, due to gene mutations, is associated with increased food intake and obesity

21. NPY (arcuate nuclei) – when energy stores of the body are low– stimulates appetite+ firing of the POMC neurons is reduced = decreased activity of the melanocortin pathway and further stimulated appetite

23. Factors That Regulate Quantity of Food Intake • short-term regulation– preventing overeating at each meal • long-term regulation– maintenance of normal quantities of energy stores in the body

24. Short-Term Regulation • What turns off the eating? • distending of gastrointestinal tract (stomach and the duodenum– vagus nerve) • humoral and hormonal factors • cholecystokinin (CCK) – fat • peptideYY from the ileum and colon– fat,?? • glucagon-like peptide (GLP) from intestines – enhances glucose-dependent insulin production and secretion from the pancreas – suppress appetite

25. ghrelin – oxyntic cells of the stomach and intestine, concentrations rise during fasting, fall rapidly after a meal; administration of ghrelin increases food intake in experimental animals; ? • oral receptors (experiment with esophageal fistula; chewing, salivation, swallowing, and tasting – shorter duration (20-40 min))

26. Intermediate and Long-Term Regulation • depends on nutritional status of the body • glucostatic, aminostatic and lipostatic theories of regulation • glucoreceptor( GUKincreases the rate of firing) andglucosensitive( GUK decreases the firing)neuronsin the hypothalamus

27. Temperature Regulation and Food Intake • exposition to cold – increased feeding • interaction within the hypothalamus: • increases metabolic rate • provides increased fat for insulation

28. Feedback from Adipose Tissue • hypothalamus senses energy storage through the actions of leptin, a peptide hormone released from adipocytes • POMC neurons of the arcuate nuclei and neurons of the paraventricular nuclei: • appetite stimulators (NPY i AGRP) • activation of POMC neurons (α-MSH) •  substances that decrease apetite(CRH) • increased sympathetic nerve activity •  insulin secretionby the pancreatic β cells

30. in mice or humans with mutations that render their fat cells unable to produce leptin or mutations that cause defective leptin receptors in the hypothalamus – marked hyperphagia and morbid obesity • in most obese humans – no deficiency of leptin production • many other mechanisms, questionable summary

31. Obesity – excess of body fat • BMI = mass(kg) / hight2(m2) • 25-30 – overweight, 30 – obese • measurment of total body fat (skin-fold thickness, bioelectrical impedance, or underwater weighing; 25% &35%) • obesity results from greater energy intake than energy expenditure

32. for each 9.3 Cal (38,9 kJ ) of excess energy – 1 gram of fat is stored • 1/3 energy used each day by the average person goes into muscular activity (2/3) • increase in physical activity!

33. Psychological factors • three meals a day and that each meal must be filling • during or after stressful situations (death of a parent, a severe illness, or even mental depression) • eating can be a means of releasing tension

34. Childhood Overnutrition • rate of formation of new fat cells • number of fat cells in obese children is often as three times that in normal children • hyperplasticandhypertrophic obesity • new adipocytes can differentiate from fibroblast-like preadipocytes at any period of life

35. Neurogenic Abnormalities • lesions in the ventromedial nuclei of the hypothalamus – tumors • functional organization of the hypothalamic or other neurogenic feeding centers in obese individuals may be different • abnormalities of neurotransmitters or receptor mechanisms

36. Genetic Factors • obesity definitely runs in families • identical twins mass is usually within 1.5, or 2.5 kg • 20-25% of cases of obesity may be caused by genetic factors • mutations of MCR-4 • congenital leptin deficiency • mutations of the leptin receptor

37. Treatment of Obesity • reducing energy intake or/and increasing energy expenditure • large quantities of "bulk“ (non-nutritive cellulose substances, distention) • prevent vitamin deficiencies • amphetamines, sibutramine– dangerous, overexcite sympathetic nervous system and raise pressure, addiction

39. altering lipid metabolism • orilistat(a lipase inhibitor) – reduces the intestinal digestion of fat • loss of fat-soluble vitamins in the feces • increase in physical activity • various surgical procedures (gastric bypass surgery and gastric banding surgery)

41. Inanition • lack of food, or • psychological and hypothalamic disorders • anorexia nervosa – reduction in food intake caused primarily by diminished appetite, nauseated by food • cachexia – weight loss greater than that caused by reduced food intake alone (tumors, AIDS)

42. Starvation • tissues preferentially use carbohydrate for energy • protein depletion: rapid depletion at first, then greatly slowed depletion, and, finally, rapid depletion again shortly before death • gluconeogenesis decreases to 1/5 • state of ketosis(β-hydroxybutyrate– brain)

44. Body Temperature Regulation and Fever

45. Normal Body Temperatures • “core” temperature = ± 0,6 ºC (± 1 ºF) (nude person exposed to air temperatures 10-55 ºC, beautifully designed control system) • skin temperature rises and falls with the temperature of the surroundings (ability to lose heat to the surroundings)

46. Normal Core Temperature • range of normal temperatures (36-37,5 ºC) • average normal core temperature 36,5-37 ºC (measured orally; rectally 0,5 ºC higher) • regulatory mechanisms are not perfect: temperature increases during exercise and varies with temperature extremes of the surroundings • balance between heat production and heat loss

48. Heat Production • heat – principal by-product of metabolism • metabolic rate of the body: • basal rate of metabolism • muscle activity • effect of thyroxine, (hGH, testosterone) • effect of sympathetic stimulation • increased chemical activity in the cells • thermogenic effect of food

49. Heat Loss • heat is generated in deep organs: liver, brain, and heart, and in the skeletal muscles • heat is lost to the air via skin • rate at which heat is lost: • how rapidly heat can be conducted from where it is produced to the skin • how rapidly heat can then be transferred from the skin to the surroundings

50. Insulator System of the Body • skin, subcutaneous tissues (fat) – insulator • conduction of heat through fat = 1/3 conduction through other tissues • insulator properties of female body are better than malebody