The Biology of Hunger

Inputs to satiety-sensitive cells in arcuate nucleus?

- CCK (from intestinal distention); short term signal - blood glucose; short term signal - insulin; intermediate term signal - body fat; long term signal - leptin; long term signal

What happens in the large intestines?

- absorbs water and minerals - lubricates remaining material to be passed as feces

What does insulin do?

- allows glucose to enter cells (except brain cells, which don't need insulin to enter)

How does the lateral hypothalamus contribute to feeding?

- axons from the lateral hypothalamus to the nucleus of the tractus solitarius (NTS) alter the taste sensation and the salivation response to the tastes. When the lateral hypothalamus detects hunger, it sends messages to make food taste better - axons from the lateral hypothalamus extend into parts of the cerebral cortex, facilitating ingestion and swallowing, and sensitizing cortical cells to the taste, smell and sight of food - increases pituitary gland's secretion of hormones that increase insulin secretion - sends axons to the spinal cord, controlling autonomic responses such as digestive secretions

What happens when mothers consume a high-fat diet during pregnancy?

- baby will develop larger than average lateral hypothalamus - thus, baby will produce more than the average amount of orexin and other transmitters that facilitate eating

Examples of syndromal obesity?

- chromosome deletion can cause severe, early-onset obesity - Prader-Willi syndrome: causes mental retardation, short stature, and obesity as a result of blood levels of ghrelin 4-5 times higher than average

What happens when you damage the lateral hypothalamus? When you stimulate it?

- damage: animal refuses food and water and may starve to death unless force-fed; gradually recovers much of its ability to eat - stimulation: increases drive to eat

What causes satiety?

- distension of stomach or duodenum

How does bulimia resemble drug addiction?

- eating tasty foods activate same area as addictive drugs - drug addicts who cannot get drugs sometimes overeat as a substitute - food-deprived people and animals are more likely than others to use drugs

What happens in the stomach?

- enzymes digest proteins - stores food for a time until food is released into small intestine

How did the gene for lactose digestion come about?

- evolved independently in different places - ex. Europeans have different lactose-digesting genes than Africans, Africans have different genes from other - probably evolved in response to domestication of cattle

How does the duodenum cause satiety?

- fat in duodenum releases oleoylethanolamide (OEA) and cholecystokinin (CCK) - OEA stimulates vagus nerve which sends message to hypothalamus to delay next meal - CCK constricts sphincter between stomach and duodenum, causing stomach to hold its contents and distend - CCK stimulates the vagus nerve to send signals to the hypothalamus to release CCK as a neurotransmitter which triggers decreased feeding

What happens to rats with VMH damage who are prevented from overeating?

- gain weight anyways - rat does not gain weight from overeating - rather, rat overeats because its body stores too much fat

Describe the insulin/glucagon feedback system

- hunger causes eating - eating causes blood glucose increase - blood glucose increase causes insulin increase - insulin allows glucose to enter cells for use or storage - increased glucose in cells decrease hunger - decreased hunger blood glucose to decline - decreased blood glucose decreases insulin levels - glucagon release increases - increased glucagon releases stored supplies as glucose which enters blood, which lowers return of hunger

When do people tend to eat the most?

- in the fall

In what species is leptin found?

- in vertebrates only

What happens when insulin levels are constantly low?

- increase eating - b/c glucose isn't entering cells - cells are starving - glucose mostly excreted, weight is lost

Biochemical levels of those with bulimia?

- increased ghrelin production - most likely as a result of the binges and purges as opposed to a cause, b/c biochemical levels return to normal levels after therapy

Effect of lesion in the ventromedial hypothalamus?

- increased meal frequency - weight gain - high insulin level

Effect of lesion in the paraventricular nucleus?

- increased meal size - especially increased carb intake during the first meal of the active period of the day

What happens when insulin levels are constantly high?

- increases eating - b/c blood glucose rapidly stored so hunger returns quickly - weight gain

What does the ventromedial hypothalamus (VMH) do? What if it's damaged?

- inhibits feeding - damage = overeating and weight gain (but damage must extend outside ventromedial nucleus to nearby axons, especially the ventral noradrenergic bundle)

Paraventricular nucleus (PVN)

- input from arcuate nucleus - inhibits the lateral hypothalamus, an area important for eating - important for satiety - rats with damage in the paraventricular nucleus eat larger than normal meals

How do most drugs control appetite?

- insulin, diet drugs, and other procedures affect eating mostly by altering input to the melanocortin receptors

Why do lactase levels decline at the age of weaning?

- may be an evolved mechanism to encourage weaning at the appropriate time

Why do mammals stop nursing?

- milk supply declines - mother pushes them away - begin to eat other foods

What happens in a mouse with the obese gene?

- no leptin is produced - body acts as if it has no fat stores and is starving - mouse eats as much as possible - conserves energy by not eating much - fails to enter puberty

How does sugar affect children's behaviour?

- no significant effect on children's activity level, play behaviours, or school performance

Can CCK be used to help weight loss?

- no, because CCK only has short term effects - limits meal size, but animal who has eaten a smaller meal than usual will compensate by overeating at next meal

What is syndromal obesity?

- obesity resulting from a medical condition

What kinds of neurons are found in the arcuate nucleus?

- one set that's sensitive to hunger signals - one set that's sensitive to satiety signals

What is orexin and what is its role in feeding?

- orexin (aka. hypocretin) related by lateral hypothalamus - two roles: 1) increases animals' persistence in seeking food 2) responds to incentives or reinforcement in general - ex. eating ice cream in spite of not feeling hungry; happens b/c pleasant taste activates orexin receptors that override satiety messages from other receptors

How to reverse leptin insensitivity caused by obesity? How does it work?

- physical exercise - causes production of chemicals of the immune system which repairs ER

What can cause leptin insensitivity?

- pregnancy - preparation for hibernation - obesity: consistent overeating leading to obesity damages cell ER in hypothalamic neurons, which leads to leptin insensitivity

What happens in the small intestines?

- proteins, fats and carbs are digested - digested materials are absorbed into bloodstream

How does the arcuate nucleus influence the PVN?

- satiety-sensitive cells send excitatory signals via the neuropeptide alpha-melanocyte stimulating hormone (aMSH), which is a melanocortin - melanocortin receptors in PVN important for limiting food intake - hunger-senstive cells inhibit both the PVN and the satiety-sensitive cells using GABA, neuropeptide Y (NPY), and agouti-related peptide (AgRP), thus blocking satiety actions of the PVN

How does leptin work?

- signals brain about fat reserves and provide long-term indication of whether you've overeating or undereating - also indicates something about short-term nutrition

What are the best treatments for weight loss?

- small changes in diet - changes in lifestyle: increased exercise and decreased eating - reduce or eliminate the intake of soft drinks - weight-loss drugs, such as sibutramine (Meridia) which blocks reuptake of serotonin and norepinephrine and decreases meal size and binge eating, or orlistat (Xenical) which prevents intestines from absorbing up to 30% of fats in the diet - last resort is gastric bypass surgery

Is stomach distension sufficient and necessary for satiety?

- sufficient, but not necessary

Inputs to hunger-sensitive cells in arcuate nucleus?

- taste pathway: good-tasting food stimulates hunger - ghrelin - a neurotransmitter that binds to the same receptors as growth-hormone releasing hormone - the only known hunger hormone - ghrelin triggers stomach contractions during food deprivation - ghrelin also acts on hypothalamus to decrease appetite and acts on hippocampus to enhance learning

How does eating a high-carb diet increase sleepiness?

- tryptophan enters brain by the same active-transport proteins that transport phenylalanine and other large amino acids - when you eat carbs, body releases more insulin, which moves the phenylalanine into storage along with the sugars from the carbs - less competition from phenylalanine = more tryptophan in the brain - tryptophan helps brain produce melatonin

What happens when you have high leptin levels?

- usually indicates that you have adequate fat stores - eat less - become more active - increase activity of immune system - enables an adolescent to enter puberty (b/c you need to not be starving to be able to provide for a baby)

How does the stomach cause satiety?

- via the vagus nerve and splanchnic nerves - vagus nerve (cranial nerve X) conveys info about stomach wall stretching - splanchnic nerve conveys info about nutrient contents of the stomach

What begins being digested in the mouth?

-enzymes in saliva start breaking down carbohydrates

How does damage to the VMH differ from damage to the PVN in terms of feeding behaviour in rats? Why?

Damage to PVN: rats eat larger meals Damage to VMH: rats eat more frequent, normal-sized meals B/c rats with VMH damage have increased stomach motility and secretions, resulting in the stomach emptying faster. Also, VMH damage increases insulin production, which increases storage as fat

Is taste and other mouth sensations sufficient for satiation?

No. Sham-fed animals do not become satiated. Neither is just receiving nutrients from a rubber tube - untasted meals are unsatisfying too

What's the role of the digestive system?

To break food down into smaller molecules that cells can use

What is bulimia nervosa?

condition in which people alternate between binges of overeating and periods of strict dieting

Effect of lesion in the lateral preoptic area?

deficit in osmotic thirst due partly to damage in cells and partly to interruption of passing axons

Effect of lesion in the preoptic area?

deficit in physiological mechanisms of temperature regulation

What's the most common single-gene cause for obesity? Another less common cause?

most common: mutation in the gene for melanocortin receptors other cause: variant form of FTO gene

What is the master area in the brain for control of appetite?

the arcuate nucleus in the hypothalamus

Effect of lesion in the lateral hypothalamus?

undereating, weight loss, low insulin level (b/c of damage to cell bodies) underarousal, underresponsiveness (b/c of damage to passing axons)