Nutrition 3 - Physiology of feeding and satiety Flashcards Preview

1st Year - Gastroenterology > Nutrition 3 - Physiology of feeding and satiety > Flashcards

Flashcards in Nutrition 3 - Physiology of feeding and satiety Deck (51):
1

Energy Homeostasis

Physiological process whereby energy intake is matched to energy expenditure over time

2

What 2 factors cause obesity?What are the 2 major factors that influence obesity

Accessible, tasty calorie dense foodSedentary lifestyleGeneticsEnvironment

3

What is metabolic syndrome (syndrome X)?

Central obesity plus 2 of:Blood pressure greater than or equal to 130/85Triglycerides greater than or equal to 1.7 mol/LHDL less than 1.03 in males and 1.29 in females (mol/L)Fasting glucose greater than or equal to 5.6mmol/LDiabetes mellitus

4

Possible consequences of metabolic syndrome? (4)

CV diseaseDibetes MellitusGallstones CancersMore in list

5

What is the equation for BMI?

Wegith (kg) / square of height (m)

6

Categories of BMI?

Up to 25 = thin or normal25-29.9 = overweight30-39.9 = obesegreater than or equal to 40.0 = morbidly obese

7

What are some of the consequences of obesity (9)

Stroke (hypertension)Respiratory disease (sleep apnoea)Heart disease (lipids, diabetes, hypertension)Gallbladder diseaseOsteoarthritisDementiaNAFLD (fatty liver)DiabetesCancer(Uterus, breast, prostate, colon)Hyperuricemia, gout

8

Why do we need fat? (3)

Energy storagePrevention of starvationEnergy buffer during prolonged illness

9

What is one of the reasons why it is difficult to lose weight?

Increased fat alters brain function in order that the brain views the fat as normal and dieting as a threat to body survival

10

How does the CNS influence energy balance and body weight (3)?

Behaviour - feeding and physical activityANS activity - regulates energy expenditureNeuroendocrine system - secretion of hormones (integration of these determines final output - feeding behaviour)

11

Where does the CNS influences on energy balance get integrated (in order to produce final behaviour)How do we know this

In the hypothalamus in the brain Lesioning ventromedial hypothalamus causes obesityLesioning lateral hypothalamus causes leaness

12

What 3 basic concepts underline the control system of energy intake and body weight?

Satiety signallingAdiposity negative feedback signallingFood reward

13

What is satiation?

Sensation of fullness generated during a meal

14

What is satiety?

Period of time between termination of one meal and the initiation of the next

15

What is adiposity?

The state of being obese

16

What does the satiation and satiety processes regulate?

Meal intimation, termination and inter-meal frequency

17

When satiation signals increase

During meal to limit meal size

18

What are the satiation signals? (5)

Cholecystokinin (CCK)Peptide YY (PYY3-36)Glucagon-like peptide 1 (GLP-1)Oxyntomodulin (OXM)Obestatin

19

Cholecystokinin (CKK)?

Secreted from enteroendocrine cells in duodenum and jejunumReleased in proportion to lipids and proteins in mealSignals via sensory nerves to hindbrain and stimulates hindbrain directly (Nucleus of solitary tract)

20

Peptide YY (PYY3-36)?

Secreted from endocrine mucosal L-cells of GI tract Levels increase rapidly post-prandiallyInhibits gastric motility, slows emptying and reduces food intake (Hypo)

21

Glucagon-like peptide 1 (GLP-1)

Product of pro-glucagon geneAlso released from L cells in response to food ingestionInhibits gastric emptying reduces food intake (Hypo, NTS)

22

Oxyntomodulin (OXM)?

Also from pro-glucagon gene and released from oxyntic cells of small intestine after mealActs to suppress appetite - mechanism unclear

23

Obestatin

Peptide produced from gene that encodes gherkin and released from cells lining stomach/ small intestine Suggested t reduce food intake - may act to antagonise the actions of gherkin - actions unclear at present

24

What is a hunger signal?

Ghrelin

25

What is Gherkin?Where is it produced and secreted?How do its levels range?

Octanoylated peptideOxyntic cells in stomachLevels increase before meals and decrease after mealsLevels are raised by fasting and hypoglycaemia

26

What does peripheral gherkin stimulate?what does it decrease?

Food intake (hypo) and decreases fat utilisation

27

What doe gherkin-containing neurons in the hypothalamus do?

Help control fat metabolism, increasing lipogenesis (liver and adipose)

28

What do feedback loops which control overall energy balance do?How does this work basically?

they act to maintain constancy of total body energy stores - why weight is stable in lean and obese individualsSignals are produced in response to body nutritional statusThese are sensed in the hypothalamusThese act to modulate food intake and energy expenditure

29

What central appetite controllers increase food intake when injected into the hypothalamic centres? (3)

GlutamateGabaOpiods (effects modest/ short lasting)

30

What central appetite controller acts to suppress food intake?

Monoamines (many drugs developed to suppress food intake but most were withdrawn due to side-effects)

31

What do adiposity signals do?

2 hormones produced in peripheral tissues which act on the hypothalamic neurones communicating the status of fat stores

32

What are the 2 adiposity signals?Where are these each made and released from?What does these both do?

Leptin - fat cellsInsulin - pancreatic cellsInform the hypothalamus to alter energy balance and eat less and increase energy burn

33

What does reduced leptin do?(in mice with a mutation in the leptin gene)

Mimic starvation causing unrestrained appetite

34

What happened in mice with no receptor for leptin therefore meaning no leptin resulting?

They became severely obese (also hyperglycaemic, hyperinsulinemic, insulin resistant)

35

What are some of the biological roles of leptin (7)?

Pleiotropic hormoneFood intake/ energy expenditure/ fat depositionPeripheral glucose homeostasis/ insulin sensitivityMaintenance of immune systemMaintenance of reproductive systemAngiogenesisTumourigenesisBone formation

36

What does insulin circulate in the body in proportion to?What has a high levels of insulin receptors?What does intracerebroventricular insulin do in rodents? (2)What does neutron specific deletion of the insulin receptor result in?

Proportion to body adiposityThe hypothalamusInhibits food intake and decreases body weight Obesity

37

What is it in food that is thought to give you pleasure?

SugarFat(important role in dopamine pathways)

38

Why is the use of leptin theraputically to treat obese patients limited?

Most obese individuals have severe petit resistance (they have characteristically high leptin levels)

39

What are the 2 main theories for leptin resistance in diet-induced obesity?

Defective leptin transport into brainAltered signal transduction following leptin binding to its receptor

40

Previous drugs for treatment of obesity - Noradrenergics?

Noradrenergicsdiethylpropion (Tenuate)MazindolPhentermine (USA not UK)Appetite suppressants acting to inhibit noradrenaline uptake CV side-effects

41

Serotonergics?

FenfluramineDexfenfluramineFluoxetineAppetite suppressants acting on 5-HT systemFen. and Dex. no longer used - induced heart diseaseFluoxetine effects on weight modest and weight returned therefore no longer prescribed in the USA/UK

42

What is Fen-Phen?

Combination of fenluramine and phentermine - very effective but caused potentially fatal pulmonary hypertension and heart valve problems so has therefore been withdrawn

43

What is Sibutramine?

Selectively inhibits re-uptake of noradrenaline, 5-HT and dopamine. Decreases food intake and may also increase thermogenesis. Effective - though limited (10lbs lost in 1 year) Major concerns over side-effects (cardiovascular events and strokes) Withdrawn (2010), but can be purchased on-line in weight-loss products

44

Present drug for treatment of obesity?How does it workSide effets?

Orlistat (Senical or Alli)Inhibits pancreatic lipase decreasing triglyceride absorption Reduces efficiency of fat absorption (~30%) in small intestine Side-effects include cramping and severe diarrhoea Need to take vitamin supplements (fat soluble vitamins) May not be particularly effective over long-term (weight loss small (3 kg in 12 months,get ‘rebound’ in weight)

45

what was the latest anti-obesity drug to fail?Other uses for this drug?Why has it been withdrawn?

Rimonabant Atcs on the endocannabinoid system (system targeted by marijuana active components)Causes a reduction in appetiteSmoking cessationReducing addiction to certain drugsImproved short-term memoryCauses severe depression, anxiety and increased risk of suicide

46

Anti-Obesity drugs currently being developed? (3)

Lorcaserin: (Belviq) An agonist at 5-HT2c receptors – designed to target a different site to fenfluramine (5-HT2b). Inferior to rimonabant or sibutramine in efficacy (3%). Safety issues raised in 2010 and 2012. FDA approved in June 2012; EMA rejected (2013)Qsymia: Combination therapy – phentermine + topiramate (an anticonvulsant). Weight loss in DIO rats better than sibutramine or rimonabant (5-10%). FDA rejected. But dosage of each drug in Qsymia reduced – Approved in July 2012; EMA rejected (2013)Contrave: Combination of bupropion (dopamine re-uptake inhibitor) + naltrexone (opioid antagonist). Effective in obese subjects (~5%). FDA declined in 2011. Cardiovascular safety issues. Further studies and FDA recommended approval in 2014 EMA recently approved (2015) – marketed as Mysimba in EU

47

New anti-obesity drug currently coming on-line?

Liraglutide (Saxenda)Licensed for treatment of type 2 diabetes, causes weight lossGlucagon-like peptide 1 receptor agonist (GLP-1 - a satiety peptide)Higher doses than used for diabetes produce significant weight lossFDA approved for obesity treatment, December 2014EMA recommended for approval January 2015Mechanism for anti-obesity action unclear – has to be injectedSome concerns remain regarding thyroid and pancreatic cancer

48

Advantages of gastric by-pass surgery?

Produces substanioncal and sustainable weight lossInduces a high level of complete resolution of type 2 diabetesBy-pass restricts calorie intake and induces malabsorption of nutrients but resolution of T2D is unclear (involves altered secretion of peptides from the stomach and gut)

49

What is adaptive thermogenesis

regulated production of heat in response to environmental changes in temperature and diet, resulting in metabolic inefficiency

50

What do thermogenic adipocytes do?

Increase energy expenditure uncoupling of oxidative metabolism from ATP production

51

What is the key function of uncoupling protein 1 (UCP 1) (fatty acid activated protein)

Short circuits proton gradient in mitochondria, accelerates fuel oxidation and produces heat