Dietary Balances Regulation of Feeding and Obesity

1. Dietary BalancesRegulation of Feeding and Obesity Prof. Dr. Bayram Yılmaz Yeditepe University Faculty of Medicine Department of Physiology

2. Energy intake and output are balanced • Under steady-state conditions, egergy intake and output are balanced • Energy available in foods: • The energy liberated from each gram of carbohydrate as it is oxidized to CO2 and H2O is 4.1 Calories (= 1 kilocalorie) and that liberated from fat is 9.3 Calories • Carbohydrates: 4 • Fat: 9.3 • Protein: 4

3. Protein, Fat and Carbohydrate Content of Different Foods

4. Energy intake and output are balanced • Average daily requirement for protein is 30-50 gr • Carbohydrates and fats act as “protein sparers” • Methods for determining metabolic utilization of proteins, carbohydrates and fats • Nitrogen excretion can be used to assess protein metabolism • Average protein contains about 16 % nitrogen • Urinary excretion of nitrogen in the form of urea, uric acid and creatinin (>90%)

5. Respiratory Quotient • RQ is the ratio of CO2 production to O2 utilization • It can be used to estimate fat and carbohydrate utilization • 1 CO2 molecule to 1 mole O2 in carbohydrate metabolism • When fat is oxidized, an average of 70 mol of CO2 is formed for each 100 mol of O2 used • Respiratory exchange ratio

6. Respiratory Quotient • Immediately after a meal, almost all the food that is metabolized is carbohydrates (RQ approcahes 1.0) • About 8 to 10 hours after a meal, the body has already used up most of its readily available carbohydrates, and RQ approaches 0.70 • In untreated diabetes mellitus, little amount of carbohydrates can be used by the body’s cells, so RQ is about 0.70

7. Regulation of Food Intake and Energy Storage • About 27 % of the energy ingested normally reaches the functional systems of the cells • Much of this is eventually converted to heat generated as a result of protein metabolism, muscle activity and activities of various organs and tissues • In athletes and laborers, energy expenditure for the high level of muscle activity may be as high as 6000 to 7000 Calories per day • A little more than 2000 Calories for sedentary individuals

8. Hypotalamus

9. Hypothalamus

10. Neural Centers Regulate Food Intake • The hypothalamus contains hunger and satiety centers • LHA serves as feeding (hunger) center (hyperphagia) • VMN serves as satiety center (aphagia) • PVN, DMN and ARN also play a major role in regulation of food intake • Lesions of PVN cause excessive eating • Whereas lesions of the DMN usually depress eating behavior • Chemical cross-talk among hypothalamic neurons

11. Feedback mechanisms for control of food intake

12. Nörokimyasal ve Elektriksel Uyarılar

13. Orexigenic and antiorexigenic substances • Neurotransmitters and hormones that influence feeding and satiety centers in the hypothalamus

14. Control of energy balance by two types of neuronal networks

15. Neural centers that influence the mechanical process of feeding • Sectioning the brain below the hypothalamus and basic mechanical features of feeding process • Salivation, licking lips, chewing food and swallowing can be controlled by the brain stem • Neural centers higher than the hypothalamus also play important roles in the control of feeding, particularly apetite (Amygdala and Prefrontal cortex) • Amygdala is a major part of the olfactory system

16. Factors that regulate quantity of food intake • Short-term regulation: • Gastrointestinal filling inhibits feeding • GI hormonal factors suppress feeding • CCK is released mainly in response to fat entering the duodenum and has a direct effect to reduce subsequent eating • Peptide YY is secreted from the entire GI tract, but especially from ileum and colon • High levels of PYY decreases food intake

17. The discovery of ghrelin • Identified in 1999 by Kojima and Kangawa • 28 amino-acid, orexigenic peptide hormone • Two major roles • GH regulation • Energy balance

18. Ghrelin release • Secreted from P/D1 cells in the human stomach • Derived from Pro-ghrelin molecule • Two forms • Acylated (active) • Des-acylated (inactive, 90%)

19. Ghrelin levels increase before meals and declines after the meal Injection of exogenous ghrelin will increase hunger Ghrelin receptors are also localized in the brain, especially in the hypothalamus blood ghrelin time of day Ghrelin Hypothalamus

20. Ghrelin • Potential biological role: • Feedback to hippocampus • Enhance neural connections • Improve problem-solving and cognitive abilities

21. Intermediate and Long Term Regulation of Food Intake • Effect of blood concentrations of glucose, amino acids and lipids on hunger and feeding • Glucostatic theory of feeding • Aminostatic and lipostatic theories of regulation • 1) A rise in blood glucose level increases firing rate of glucoreceptor neurons in the satiety center in the VMN and PVN • 2) The same increase in blood glucose level simultaneously decreases firing rate of glucosensitive neurons in the LHA • Temperature of regulation and food intake: cold increases food intake

22. What is Leptin? • A peptide hormone which is coded for by the obese gene (ob) • Influences the quantity of food consumed relative to the amount of energy expended • When leptin levels are high, appetite is reduced and energy expenditure is increased • Leptin has been found in gastric epithelium, placenta and adipose tissue • Most abundant in white adipose tissue

23. White Adipose Tissue (WAT) • Composed mainly of adipocytes (fat cells) • Store energy in the form of triglycerides in times of nutritional affluence • Release free fatty acids during nutritional deprivation • WAT mass is determined by the balance between energy intake and expenditure • This is influenced by genetic, neuroendocrine, and environmental factors • Under normal conditions this system is carefully regulated so that WAT mass remains constant and close to well defined ‘set point’ • Disruption of the steady state can lead to chronic decreases or increases in the quantity of WAT • Decreased amounts are associated with weight alterations during periods of diet, malnutrition, eating disorders, etc • Increased amounts indicate obesity

24. Regulating Food Intake andEnergy Expenditure • Leptin binds to its receptor which is expressed primarily in the brains hypothalamus region • In turn the hypothalamus modulates food intake and energy expenditure • When low leptin levels are detected, the body is warned of limited energy supplies • If high leptin levels are detected, the hypothalamus senses the body as being overweight • This then triggers the body to eat less and expend more energy • When energy intake and output are equal, leptin reflects the amount of triglyceride stored in the bodies adipose tissue

25. Metabolic Effects of Leptin • Decreases intracellular lipid concentration through reduction of fatty acid and triglyceride synthesis and a concomitant increase in lipid oxidation • It has been postulated that leptin inhibits acetyl-CoA carboxylase • Enzyme involved in the committed step of fatty acid synthesis • This inhibition leads to decrease in malonyl-CoA levels • Together the inhibition of acetyl-CoA to malonyl-CoA encourages the mobilization of fatty acids from storage sites and simultaneously discourages synthesis

26. Leptin • Stimulation of leptin receptors in the hypothalamus initiates multiple actions that decrease fat storage: • 1) Decreased production of appetite stimulators (NPY) • 2) Activation of POMC neurons and release of a-MSH • 3) Increased production in the hypothalamus of substances that decrease food intake (such as CRH) • 4) Increased sympathetic nerve activity • 5) Decreased insulin secretion by the pancreatic beta cells which decreases energy storage

27. Obesity • BMI = weight in kg / Height m2 • BMI is not a direct measure of adiposity and does not take into account the fact that some individuals have larger muscles • Obesity is defined as 25% or greater total body fat in men and 35% in women • Skin-fold thickness • Bioelectrical impedance • BMI analysis

28. Obesity