TEST 4: Obesity Flashcards
Obesity overview
Definition
Criteria
Kids
(Lecture, p. 723)
-A metabolic disorder that develops when calorie intake exceeds energy expenditure over time in genetically susceptible individuals
-In adults, obesity= BMI > 30
-Class 1: BMI 30 to 34
-Class 2: BMI 35 to 39
-Class 3: BMI > 40 “severe”
-In kids:
-BMI > 95th percentile for age and gender
—120% of 95% peregrine or greater OR 35 kg/m2 or greater
Adipose tissue
What is it?
What are the types (4)
(P. 723)
-Provides insulation and mechanical support
-Body’s major energy reserve to fuel other tissues
4 types:
-White
-Brown
-Beige
-Bone marrow
GEM- MOST fat in the body is white
White adipose tissue (WAT)
What is it?
Where is it?
What does it do?
(P. 723, AO)
-Comprises the majority of adipose tissue in the body
-Located in visceral (central) and subcutaneous (peripheral) stores
-Contributes to the regulation of energy homeostasis:
-Crucial for storing excess energy in the form of triglycerides and releasing that energy when needed
-in excess, contributes to obesity and metabolic disorders (increases insulin resistance and inflammation)
Adipokines deregulated vs.
Adipocytes regulated
726-727
Adipokines:
Leptin, adiponectin, resistin, RBP-4 when deregulated:
-HTN, CVA. Obesity, DM, Arthritis, metabolic syndrome, NASH
Adipocytes when regulated (a million types listed):
-Appetite, satiety, insulin sensitivity, fat distribution, energy, blood pressure, metabolic health
White adipose tissue
Contribution in times of excess
(P.723)
When the energy balance is positive, excess fat is stored in white Adipocytes:
-Cells hypertrophy and become hyperplastic
-Causes dysregulation of adipokines—> pro inflammatory state and altered lipid metabolism—> contributes to obesity comorbidities
Altered Adipocytes—> insulin resistance (lipolysis and release Of FFA)—> macrophage infiltration (TNF-alpha and IL-6)
Appetite and satiety control
Where in the brain?
Neuron types?
Peptides?
(AO, slides)
-Controlled by arcuate nucleus in the hypothalamus (responsible for balancing metabolism)
-Arcuate nucleus has 2 types of cells:
1. Orexogenic neurons: stimulate appetite decrease metabolism
2. Anorexic neurons: suppress appetite and increase metabolism
Orexins= neuro peptides that stimulate appetite
Anorexins = neuro peptides that inhibit appetite
Orexins
(P. 727)
Ghrelin:
-Produced in the stomach in response to hunger
-Ghrelin receptors in hypothalamus—> growth hormone that—> release gastric acid, increases GI motility, pancreatic secretion of insulin
-Lean people: elevate with hunger and fall after eating
-In obesity: levels remain elevated after eating (increased body weight and fat mass)
Endocannabinoids:
-Produced in the brain and peripheral nerves
-Increases appetite, nutrient absorption and lipogenesis
-Increases peripheral and central adipose tissue accumulation
Anorexins
(P.726)
Leptin:
-Produced by Adipocytes, acts on hypothalamus
-Decreases appetite and energy expenditure
-As Adipocytes increase, Leptin secretion increases
High levels of Leptin lose effectiveness (Leptin resistance) —> disrupts hypothalamus signals of satiety—> overeat—> increased weight
Glucagon-like Peptide-I :
-Stimulates pancreatic glucose dependent insulin secretion
-Decreases gastric emptying—> decreased appetite and increased satiety
Adiponectin
(P. 726)
-An Anorexin, increases energy expenditure
-Has insulin sensitizing and anti inflammatory properties
-Levels will decrease in obesity—> increased insulin resistance, increased CAD risk, and increased inflammatory markers.
Shifts in obesity from normal
Hunger
Ghrelin and endocannabinoid—> does NOT decrease after eating, so you lose the feedback loop to stop hunger (increases appetite)
Leptin, GLP-I, adiponectin—> levels are high but there is resistance, so you lose the signal to stop eating, lose the satiety sensor, and lose protective properties
Apple vs pear shape obesity
Apple:
-VISCERAL obesity: accelerated lipolysis, increased inflammation and metabolic syndromes
-Associated with HIGHER risks of obesity related health issues (of more concern)
Pear:
-PERIPHERAL obesity: fat is less metabolically active, releases fewer adipocytokines—> risk of obesity is less severe
-Associated with lower obesity related health complications (of less concern)
Obesity as multi-system syndrome
-Chronic complications are associated with > 200 health conditions
-Underlying etiologies: chronic inflammation, metabolic disorders, increased free fatty acids
Cardiovascular: Atherosclerosis, HTN, CAD, HF, renal disease, CVA
Cancer: Breast, colon, renal, stomach, pancreatic, liver, ovarian/ endometrial
GI: GERD, gallstones, fatty liver
Pulmonary: Sleep apnea, asthma exercise intolerance
Musculoskeletal: osteoarthritis, back pain, plantar fasciitis
Endocrine: insulin resistance, type 2 DM,
Infertility
Obesity treatment
-Is a chronic, relapsing disease
Treatment focus areas:
-Address metabolic abnormalities
-Lifestyle change
-CBT/ support groups
-GLP-I and GIP receptors agonists
-Bariatric surgery (Gastric bypass, roux-en-Y, gastric banding, gastric sleeve)
Leptin
(AO)
-Hormone Produced by adipose tissue
-Signals the hypothalamus to suppress appetite and stimulate energy expenditure
-In obesity, elevated leptin levels can lead to leptin resistance so its effectiveness is reduced and hunger is not suppressed (ie you always feel hungry)
-DECREASE APPETITE
Ghrelin
(AO)
-Hormone secreted by the stomach
-Known as “hunger hormone”
-Stimulates appetite and promotes food intake
-Ghrelin levels rise before meals and fall after
-In obesity, patterns are altered and Ghrelin’s suppressive effect on hunger is reduced
-INCREASE APPETITE
Insulin as hormonal regulation in obesity
(AO)
-Is released by the pancreas in response to food intake, facilitating glucose by the cells to use for energy
-Also plays a role in fat storage
-Chronic high levels of insulin (due to insulin resistance) contribute to weight gain and obesity
Other Mechanisms that affect the development of obesity
(AO)
Neurobiological:
-CNS involvement (hypothalamus plays large role in integrating signals from neurotransmitters that influence reward pathways and eating behavior)
Physical activity:
-Regular physical activity is crucial in preventing obesity and affecting basal metabolic rate
GI factors:
-Gut microbiota can affect metabolism
-GI tract releases various hormones in response to food intake (peptide YY, GLP-1) that play roles in signaling satiety and regaling energy balance
Environmental/ lifestyle factors:
-high calorie diets rich in sugar and fat
- processed foods
-socioeconomic factors
-chronic stress
What is an adipocyte?
(AO)
-Aka “a fat cell”
-Is a specialized cell that functions primarily in the storage of energy in the form of triglycerides
-Play a crucial role in storing energy and also regulating the availability of energy in the form of free fatty acids and glycerol
Adipokines
(AO)
-Hormone like cytokines secreted by adipocytes (fat cells).
-Play a huge role in regaling various metabolic and immune functions throughout the body
Brown Adipose Tissue (BAT)
(AO)
-Contains numerous mitochondria and iron, giving to its brown color
-Found in neonates and adults
-The mitochondria in them oxidize glucose and free fatty acids to generate HEAT
-In obesity, generate heat through non- shivering thermogenesis
-Does not have a role In Appetite regulation instead is considered beneficial for metabolism and energy expenditure
Beige Adipose Tissue
(AO)
-Emerges in response to extreme cold exposure and exercise (shares characteristics with both white and brown adipose tissue)
-Is associated with increased energy expenditure
-Considered PROTECTIVE against obesity as it enhances weight loss by increasing overall health energy expenditure
Bone Marrow Adipose Tissue
(AO)
-Found within the bone marrow (including long bones)
-Releases adipokines that interact with osteoblasts (plays a role in bone health)
-Excess BMAT is linked to osteoporosis and and produces inflammation that contributes to things like RA
Summary of the difference between Orexin hormones and anorexin hormones:
(AO)
Orexin:
-Grehlin and endocannabinoids increased hunger and food intake and decrease metabolism
Anorexin:
Leptin, GLP-1, and adiponectin reduce hunger and enhance feelings of satiety and also increase metabolism
Ghrelin (Orexin) Hormone
(AO)
-Produced in the stomach during periods of hunger
-Binds to receptors in hypothalamus to release growth hormone and other stomach related effects
-Stimulates appetite
Endocannabinoids (Orexin) Hormone
(AO)
-Are synthesized in the brain and peripheral nerves
-Interact with cannabinoid receptors to increase appetite and nutrient absorption
-Enhance food intake and energy storage
Leptin (Anorexin) Hormone
(AO)
-Secreted by adipocytes and act on hypothalamus to regulate energy balance
-Decreased appetite and promotes energy expenditure
-It reduces appetite although chronic high levels make it ineffective leading to weight gain
-Stress, high carbs, and poor sleep increase these levels
Glucagon-Like Peptide 1 (GLP-1, Anorexin) hormone
(AO)
-Is secreted by intestinal cells in response to nutrient ingestion, stimulating the pancreas to release insulin in a glucose- dependent manner and slows gastric emptying
-Enhances feelings of fullness and satisfaction, leading to reduced food intake
Adiponectin (Anorexin) hormone
(AO)
-Primarily produced in adipose tissue, synthesized in smaller amounts in muscle and brain
-Regulates glucose and lipid metabolism and improves insulin sensitivity
-Anti inflammatory, anti fibrotic, antioxidant effect are beneficial for metabolic health
-When levels are decreased in obesity, insulin resistance can occur and increased cardiovascular disease and inflammatory conditions
Leptin resistance
(AO)
-As body fat increases, the amount of leptin produced increases but the brain doesn’t respond to it effectively (hypothalamus becomes less sensitive to it)
-This impaired response leads to the failure of leptin to suppresses appetite
which can lead to overeating
-Ie people still feel hungry and eat more
-Leptin resistance= inability to control hunger properly (brain fails to send signals that you’re full) and decreased ability to to expend energy
Underlying etiologies of chronic complications of obesity
(AO)
- Chronic inflammation:
-Obesity is a chronic state of low grade inflammation
-Excess adipose tissue secretes pro inflammatory cytokines)
-Accumulation of abdominal fat leads to infiltration of macrophages into adipose tissue (contributing to inflammation)
-Leads to type 2 DM, cardiac disease, cancer - Metabolic disease:
-Due to alteration of normal metabolism
-Excessive visceral body fat leads to impaired insulin signaling and insulin resistance develops
-Can also cause dyslipidemia, HTN, and metabolic syndrome (increasing risk of MI/ CVA) - Increased free fatty acids:
-Increased release of free fatty acids are released from the adipocytes into the bloodstream
-Triglycerides are broken down into FFA’s, which contribute to metabolic disturbances
-Can interfere with insulin signaling, liver fat accumulation (non alcoholic fatty liver), cardiac complications, and contributes to oxidative stress and systemic inflammation
