Physiology-Ingestive Behavior and Energy Balance

• polysacchride stored in liver and muscle, part of the short term reserve
• liver converts glucose into glycogen and stores it

• hormone secreted by the pancreas that promotes glycogen in the liver to convert to glucose
• secreted when cells in the pancreas and brain detect a fall of glucose in the blood

• peptide hormone released by the stomach that increases eating
• also produced by neurons in the brain
• activates orexigenic NPY neurons
• dopaminergic neurons in the VTA contain ghrelin receptors
• administration of ghrelin in rats increased activity of DA neurons and triggered release of activity in the NAc

brings blood from the intestines to the liver

• connects the liver with the brain, brain recieves hunger signals via the vagus
• makes its first central synapse in the medulla

• dorsal= vagal afference
• ventral= vagal efference

• cut of dorsal root= 50% efference, NO afference
• afferent lesion= no CCK detected

• Highly vascular
• major contributor to heat production
• innervated by the sympathetic nervous system

• Exercise associated thermogenesis (EAT)
• non exercise (NEAT)
• diet induced thermogenesis (DIT)
• non shivering thermogenesis ex. BAT thermogenesis
• shivering

• facilitates the conversion of nutrients into heat
• expressed in brown adipose sites
• may determine metabolic efficiency

• enables scientist to know weight of a protein
• each black blob is representative of the presence of a protein

• created a mouse with no beta-adrenergic receptor
• when put into cold environment animals with no BAR has rapid decline in core temp.
• uncoupling protein activity is dependent on beta receptor

• forebrain is surgically seperated= decerberate animal
• animal and control are subjected to 3 ambient temps.
• data supports: can adequately regulate core temp without forebrain

coined by Stock and Rothwell

• experiment:
• genetically lean and obese mice (hyperphagic)

• lean mice:
• -fed mouse chow
• -fed cafeteria food= +food intake, + energy expenditure, no weight gain*

• obese mice:
• -fed mouse chow, intake amount is larger than lean mice
• -fed caferia food= +intake, +weight, slight increase in energy expenditure

preabsorptive: distention of stomach, nutrient detectors in upper intestine

post absorptive: absorbed nutrients themselves or signals related to them

• stomach= conveys volume
• intestine= detects calories and nutrients

first part of the intestines

• -contains afferent axons sensitive to presence of glucose, amino acids, and fatty acids
• -contains chemoreceptors that transmit satiety signals
• -secretes cholecystokinin (CCK) in the presence of fats

• -produced by cells in the GI tract, released after a meal in amounts proportional to the amount of calories consumed
• -satiety signal

• a hormone secreted by adipose tissue
• decreases food intake and increases metabolic rate
• primarily inhibits NPY-secreting neurons in the arcuate nucleus of the hypothalamus

• a neurotransmitter that is part of the pathway activating MCH and orexin neurons of the lateral hypothalamus
• extremely potent stimulator of food intake
• neurons that secrete NPY are mainly found in the arcuate nucleus of the hypothalamus
• activated by glucoprivation and ghrelin

• BAT injected with virus
• infected neurons identified with histochemistry
• method highlighted the pathway of BAT output neurons
• black, grey, white= 1st, 2nd, 3rd stage of infection
• Raphe Palladus (RP) is one of the first to be infected

• storage depot
• endrocrine organs- makes hormones, insulin and leptin

• BAR (beta adrenergic receptor)
• corresponding increase in leptin
• metabolic rate evaluated by oxygen intake
• no BAR= same cell shape of WAT and BAT
• beta receptors are needed to have uncoupling protein

animals can control temp. from caudal regions

• methods:
• -control rats=sham surgery
• -full decerberate rats
• -both groups implanted with transponder to take
• measurements
• -used histology to verify complete transection in decerberate rats

• Both groups exposed to temps:
• -4C
• -8C
• -12C
• HR, core temp., activity, and NE turn over were measured

• Core temp:
• -control rats maintained 37C core temp during exposure
• -CD rats showed gradual decrease in core temp. during 4C exposure
• *did NOT show significant difference in 8C, 12C exposure

• Heart Rate:
• -control rats elevation during cold exposure correlated with the reduction in ambient temp
• -CD rats not correlated with decreasing temp., HR elevation was equivalent in magnitude for each temp.

NETO in 4C: -CD rats showed significant increase in IWAT, RWAT, and IBAT but not heart in comparison to sham rats -this shows an overall increase in total body fat

• Heart NETO- indicative of general sympathetic activity
• -significantly increased by cold exposure in both groups to the same extent

• IBAT NETO: increased in both groups
• CD rats- increased 4x compared to sham group

• contributors of heat production and stability of core temp. by CD rats included:
• -increased sympathetic drives to heart and IBAT
• -elevated heart rate= increased IBAT blood flow that would facilitate the distribution of heat from IBAT thermogenesis

• -reveals a range of energetic response compentencies and local caudal brain stem control of sympathetic outflows
• -differences between CD and sham rats= thermoregulatory competence of the neutrally isolated brain stem is somewhat imcomplete

• examined involvement of autonomic brain regions in sympathetic thermogenic responses in BAT to skin cooling in rats monitored by:
• -BAT sympathetic nerve activity (SNA)
• -BAT temp.
• -metabolism (expired CO₂)
• -blood pressure
• -heart rate
• Examined the effect of chemical modulation of neurons with electrophysical activity

• Skin cooling: increases in:
• - SNA 660%
• -T_bat =.9C
• -expired CO₂=.4%
• -HR 49bpm

BUT T_rec and T_brain remained stable

altered neuronal discharge in POa, DMH, RPa showed significant change in T_bat, HR, and expired CO₂

• POa- GABAnergic transmission is critical for skin cooling-evoked stimulation of BAT thermogenesis
• DMH- probably candidate for regions receiving a tonic inhibitory input from POa in the regulation of BAT thermogenesis
• -decrease in skin cooling-evoked activity= DMH neurons are involved in the central mechanism for skin cooling-evoked thermogenesis in BAT
• RPa- critical role of medullary raphe neurons in thermogenic responses to cold environments
• -neurons in this region express Fos in response to cold exposure
• -suppression of neuronal activity in raphe palledus nucleus= hypothermia in rats under normothermic conditions

• affecting drop size, calories, etc. rats compensate to get usual amount of calories
• D-fen: appetite supressant, effect seratonin

Procedures:

• Experiment 1: rats w/ surgically implanted intraoral cannulas
• -ingested 12.5% glucose
• -D-fen or saline injected prior to each test, 2 conditions:
• -delivered continuously
• -interrupted for 10 mins. after 6 mins of infusion onset

• Experiment 2: no surgery on rats
• 2 groups= drop size 4mL/lick and 3 tests of 8 mL/lick
• -group 2 received drop size test blocks is reverse order

• -saline vehicle injected before 1st and 3rd tests of each block
• d-Fen injected before 2nd test of each block

• evaluated each conditon with 5 behavioral measures:
• -licks per sec.
• -ingestion rate mL/min
• -meal duration
• -first min. ingestion rate
• -first min. licks

only saw significant differences in first min. ingestion rate and licks between d-Fen and saline

adjustment of # of licks based on drop size= intake effect doesn't depend on d-Fen's action on general motor performance

• preabsorptive vs. postabsorptive signals
• Hypthesis: caloric ingestion is regulated through a satiety mechanism

• rats given 4 hr. feeding sessions and preloads 15 before feeding
• preloads:
• -balanced nutrients
• -carbs.
• -lipids
• -protein
• -saline

calculated difference between saline and nutrient preloads

• Results: every nutrient preload inhibits ingestion during meal
• dose response relationship to caloric content of preload

• Conclusion: taste, olfaction, and swallowing are not required for satiety
• -rise in glucose is sufficient but not required for satiety
• -satiety is an integration of several mechanisms:
• -capacity to monitor caloric concentration
• -gastric distention
• *Satiety is the behavioral outcome of monitoring and controlling caloric ingestion

• gastric bypass efficacy
• gut hormones measured:
• -PYY
• -GLP-1
• -Ghrelin
• 1st Study:
• 16 patients recieved laproscopic gastric bypass
• plasma levels of gut hormones measured preoperatively and 2,4,7 and 42 days post operatively
• visual analog scales (VAS) used to meaures hunger and fullness efore and after meals

• Study 2: Good or Poor responders
• 20 subjects chosen and best or worst responders to gastric bypass
• plasma levels of gut hormones measured before and after 400 mixed calorie meal

• Study 3: Pharmacologic inhibition of gut hormones release
• 13 subjects given bypass or laproscopic banding
• given either saline or somatostatin (blocks release of gut hormones)
• meal served 60 min. after injection
• plasma levels measured before and after injection
• VAS measured

• Study 1:
• day 2- increase in PYY and GLP-1
• VAS- hunger=1/2
• satiety= 2x
• results continued through day 42

• Study 3:
• gastric bypass showed much larger increase in gut hormones compared to banding
• somatastatin= 2x food intake for bypass patients

• bypass- levels of PYY and GLP-1 increased as soon as day 2 after operation
• caused by surgery on stomach
• inhibition of hormones= appetite recovery and normal eating behavior
• patients who lost weight successfully=higher levels of gut hormones than those who lost less weight

• leptin and control of food intake
• showed leptic receptors in medial NTS
• gastric distention regulation distention and leptin work together to reduce food intake
• Neurons in the NTS are activated by gastric distention
• active form of leptin= ObRb
• exogenous admin. of leptin= reduction in meal size NOT frequency, mechanism is to magnify satiation signal during each meal
• leptin receptors are found on neurons of NTS caudal brain stem
• ObRb signaling localized to the mNTS subnucleus

• Hypothesis: The same mNTS neurons might be activated both by leptin and GI afferent input
• leptin signaling could potentiate the effectiveness of GI signals in suppression of F.I.

• Experiment 1: Anatomical mapping of leptin responsive neurons in caudal brain stem
• -injected with leptin or vehicle, anaesthetized
• brains removed and examined PSTAT3 staining

• Experiment 2: antomical analysis of cells in caudal brain stem activated by gastric distention and leptin
• rats implanted with cannula and seperated in 4 groups:
• -balloon distention and leptin
• -sham distention and leptin
• -balloon distention and PBS (vehicle)
• -sham distention and vehicle

• Experiment 3: behavioral effects by gastric distention AND/OR leptin injection
• fasted for 15-17 hrs then received conditons:
• -distention= balloon inflated w/ saline OR sham
• -injection= leptin or vehicle
• measured cumulative intake of food 30, 60, 90 min and 24 hrs. after initial access to chow

• Experiment 1: P-STAT3 IHC in the NTS during leptin or vehicle
• -leptin can be seen as blue dots
• primarily in mNTS subnucleus
• P-STAT3 showed that leptin responsive neurons are exclusively located in the medial subnucleus of the NTS
• used nissl staining to detect subnuclei

• Experiment 2:
• used c-Fos IR imaging to show affects of gastric distention on neurons in NTS
• red dots= reactive neurons
• -very few c-Fos cells found when given sham distention
• Double fluorescence on NTS
• green= leptin fluorescence
• red= distention induced fluorescence

• part a of figure shows that distention activated a significant amount of leptin responsive cells
• double fluorescent cells= yellow dots

• Experiment 3: amount the stomach was filled affected intake over a 60 min. period
• 5mL of distention= decrease intake by 33%
• >5mL of distention= no significant effect

bar graph shows that neither leptin nor distention is significant to reduce food intake alone