feeding behavior/obesity
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Feeding Behavior/Obesity
Stefany Primeaux, PhD
Dept of Internal Medicine-EndocrinologyOffice: MEB, 7159D
Phone:568-2733Email: sprime@lsuhsc.edu
Reading for this lecture
Physiol Rev 85: 1131-1158; 2005
Why are we interested in learning about Feeding Behavior and Obesity?• The overconsumption of diets high in
calories and fat are major contributors to the current rate in obesity.
• Approximately 75 million adult Americans are considered OBESE.
• In 2009, 33% of adults in Louisiana were considered OBESE.
• Obesity is a major risk factor for cardiovascular disease, certain types of cancers and Type II Diabetes.
Medical costs approximately $147 billion/year
Outline
I. BackgroundI. Energy Balance EquationII. Obesity ratesIII. Health Consequences
II. Peripheral MechanismsI. Adiposity FactorsII. Gut Hormones
III. Central MechanismsI. Hypothalamic Circuitry
• ENERGY IN (calories consumed) = ENERGY OUT (calories burned) = weight same • Energy IN > Energy OUT= weight gain
• Energy IN < Energy OUT = weight loss
Energy Balance Equation
Energy Intake
Food/calories Consumed
Energy expenditure
Physical Activity Resting
Metabolic Rate
Energy IN Energy OUT
Estimated Daily Calorie Requirements
• Sedentary means a lifestyle that includes only the light physical activity associated with typical day-to-day life.
• Moderately active means a lifestyle that includes physical activity equivalent to walking about 1.5 to 3 miles per day at 3 to 4 miles per hour
• Active means a lifestyle that includes physical activity equivalent to walking more than 3 miles per day at 3 to 4 miles per hour
Sedentary Moderately Active
Active
Female
19-30 years old 2000 kcal 2000-2200 kcal 2400 kcal
Male19-30 years old 2400 kcal 2600-2800 kcal 3000 kcal
HHS/USDA Dietary Guidelines for Americans, 2005
Obesity is a chronic metabolic disease resulting from an imbalance between energy intake and
energy output
•Obesity is caused by the interaction of multiple genetic and environmental factors.
•Among these are: • Excessive calorie and food intake• Insufficient physical activity• Genetic predisposition• Family history of obesity• Individual metabolism• Behavioral factors
The defining feature is excess body fat
Percentage of individuals that are considered overweight or obese.
Louisiana: 1990 (10-14%) 1999 (20-24%) 2009 ( > 30%)
Overweight = Body Mass Index (BMI) >25
Obesity = BMI >30 = 5’5” and 180lbs
Health Consequences of Obesity• Coronary heart disease• Type 2 Diabetes• Cancer (endometrial, breast, colon)• Hypertension• Dyslipidemia• Stroke• Liver & gallbladder disease• Sleep apnea & respiratory problems• Gynecological problems
– (abnormal menses, infertility)
Regulation of Food Intake• Due to the numerous health consequences of obesity, there
is an emphasis on determining causes of and potential treatments for obesity.
In order to understand and provide treatments for obesity and its comorbidities, we must understand the mechanisms which regulate feeding behavior.
Control of Food Intake
Brain
Many factors control appetite and influence food intake
Absorptive vs. Post-Absorptive State
• Absorptive State – Ingested nutrients enter the blood
from the GI tract– Break down of food provides
nutrients– Some nutrients provide energy
(carbohydrates)– Up to 4 hours after a meal
• Post-absorptive State– GI tract is empty of food and
nutrients– Body’s cells must supply energy
(liver, adipose tissue)– When are we in the post-
absorptive state?We eat for energy!
Gastrointestinal Tract
Nutrient Metabolism During the Absorptive Period
Absorbed carbohydrate is primary energy source (converted to glucose) Net uptake of glucose by the liver. Some carbohydrate stored as glycogen in liver and muscle Excess carbohydrate stored as fat in adipose tissue Fat is stored in adipose tissue. Some amino acids used to synthesize body protein. Excess amino acids converted to fat.
What is the primary source of energy during the absorptive period?
Excess carbohydrates, fat and amino acids are stored as????
Nutrient Metabolism During the Post-absorptive Period
Glycogen, fat, and protein synthesis slow, net breakdown occurs Formation of glucose in the liver Gluconeogenesis in kidneys with prolonged fast. Utilization of glucose by muscle and other non-neural tissues is reduced Fatty acids released (lipolysis). Fatty acids and ketones provide most of the body’s energy supply. Brain uses glucose and starts using ketones as they build up in the blood.
What is the primary source of energy during the post-absorptive period?
Major goal is to maintain blood glucose levels
How is feeding behavior regulated?
- Why do we feel hungry? - How do we know when to start eating?-How do we know when to stop eating? - Does being overweight/obese alter our eating
behavior?
We might ask ourselves….
Central and Peripheral mechanisms regulating feeding behavior
Peripheral Mechanisms regulating Feeding Behavior
• Energy balance is regulated by central and peripheral signals
• The central nervous system responds to signals from the periphery…adipose tissue, pancreas, liver and gastrointestinal tract
What do these peripheral signals communicate?
Energy homeostasis is controlled by peripheral signals.
Stanley S et al. Physiol Rev 2005;85:1131-1158
Figure 1
Peripheral signals have a positive (+) or negative (-) effect on energy balance
What does a negative effect mean? How do these signals affect feeding behavior? Positive effect?
Peripheral Signals-Adiposity signals
Leptin• One of the most important
hormones is leptin.
• Leptin is expressed predominately in adipocytes
• Leptin levels are highly correlated with adipose tissue mass
• Food restriction decreases circulating leptin
Considine, 2002
Leptin signals energy stores
Leptin• The more fat the more
circulating leptin!
KO Mice do not express the leptin gene
Wildtype ob/ob
Ob/ob mice are hyperphagic and obese
Leptin Food Intake
White et al., 2009
Leptin Resistance
• The majority of obese animals and humans have raised plasma leptin.
• Administration of leptin in rats with high fat diet-induced obesity does not reduce food intake
• Circulating levels of leptin are higher in rats eating high fat diet
White et al., 2009
Low fat diet High fat diet
Leptin resistance occurs when there is no response to leptin
Leptin Deficiency in Humans
• Congenital leptin deficiency – Hyperphagia– Severe obesity– Hypogonadism– Impaired immunity
Leptin treatment reduced food intake up to 80%
Farooqi & O’Rahilly, 2009
Ghrelin• Endogenous agonist of the
growth hormone receptor
• Produced and released primarily by the stomach
• Orexigenic hormone
• Regulated by diurnal rhythms and food intake
Peripheral Signals: Gut Hormones
The only orexigenic gut hormone!What does this mean???
Ghrelin• Plasma ghrelin levels are highest
during fasting and fall after a meal
• Postprandial reduction in ghrelin is regulated by caloric intake and circulating nutritional signals (glucose)
• Circulating ghrelin is inversely related to adiposity.
Obese < ghrelin
• Ghrelin administration increases food intake in rodents and humans
Druce et al., 2005
Humans
Energy homeostasis is controlled by peripheral signals.
Peripheral signals have a positive (+) or negative (-) effect on energy balance
How do these peripheral signals influence the brain???
Central Control of Feeding Behavior
• Brain plays a critical role in the regulation of energy homeostasis
• CNS circuits instantly assess and integrate peripheral metabolic, endocrine and neuronal signals
• CNS coordinates a response that modulates both behavioral patterns and peripheral metabolism according to acute and chronic requirements
• Two main types of afferent inputs to the brain from the peripheral organs that are relevant for energy homeostasis: Hormones & Neurons
Communication between the peripheral signals and the brain
Stanley et al. 2005
Fig. 4
Brain
Periphery—Hormones in circulation
NeuronalVagus Nerve
J Endocrinol. 2005 Feb;184(2):291-318
The central control of appetite and feeding behavior
• Hypothalamus is considered the main integrator and processor of peripheral metabolic information
• Brain stem plays an important role in these processes
• Other brain regions that influence feeding
Interconnected regions
Lesions of specific regions of the hypothalamus induce starvation (LH) or obesity (VMH)
Hypothalamic Lesion StudiesVentromedial Nucleus of the Hypothalamus
Rat continues to eat as long as it is provided with palatable food
Lateral Hypothalamus Lesions
Rat decreased food intake, also have sensory and motor deficits
Arcuate Nucleus of the Hypothalamus
• Arcuate Nucleus plays pivotal role in integration of signals regulating appetite
• Contains receptors for peripheral hormones• Contains two key peptidergic systems: Neuropeptide Y and
POMC (α-MSH)
Stanley S et al. 2005
PYYInsulinLeptin
Ghrelin
Central Signals: Neuropeptide Y• One of the most abundant and
widely distributed neuropeptides in the CNS
• ARC is the major site of NPY expression
• NPY mRNA and release increase with fasting and decrease with feeding
• Binds to g-protein coupled receptors Y1—Y6, which are located throughout the brain
Ventromedial /Arcuate Nucleus
Fed Fast Refed0
0.5
1
1.5
Neu
rope
ptid
e Y/
cycl
ophi
lin
mR
NA
(A.U
.)
*
Primeaux, unpublished
Neuropeptide Y• Most potent orexigen
known!!
• Administration of NPY increases food intake, inhibits thermogenesis, suppresses sympathetic nerve activity, reduces energy expenditure
• Also involved in alcohol intake, anxiety, seizure activity
Larsen et al., 1999Rhesus monkeys
Central Signals: Melanocortin System• Comprised of the peptide products of
POMC cleavage, their receptors– α-MSH is one of the most potent
anorexigenic brain signals.– AgRP is an endogenous ligand of
melanocortin receptors, acts as an inverse agonist
• MC3R and MC4R play a role in energy balance
• POMC gene mutations or abnormal POMC peptide processing result in early-onset obesity and red hair
• Approximately 4% of cases of genetic obesity in humans
Arcuate N.
Melanocortin System
This 5-yr-old boy is heterozygous for a mutation in MC4R. In addition to early-onset obesity and hyperphagia, this child has increased lean mass, accelerated linear growth, and severe hyperinsulinemia.
Daily energy intake in male mice receiving normal or high fat chow
Notice Yellow Coat
-/- POMC KO mouse
1. Peripheral Regulation of feeding behavior1. Adiposity Signals: Leptin2. Gut Hormones: Ghrelin
2. Central Regulation of feeding behavior1. How peripheral signals
affect the brain2. Hypothalamus3. Major Neuropeptides
involved in feeding1. NPY2. POMC
We have discussed:
What other factors influence Feeding Behavior?
Morrison & Berthoud, 2007
Modulatory Factors
Genetic & Epigenetic
Visual, olfactory, auditory
Taste
Non-homeostatic consumption
Outline
I. BackgroundI. Energy Balance EquationII. Obesity ratesIII. Health Consequences
II. Peripheral MechanismsI. Adiposity FactorsII. Gut Hormones
III. Central MechanismsI. Hypothalamic Circuitry
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