Adipose and Obesity Flashcards
How is obesity assessed? What is the occurrence?
- assessed by BMI (body mass index)
- more than 60% of adults in US
What are the exceptions to BMI?
- correlates with amount of body fat (not direct measure)
- athletes and pregnant women
How does body shape correlate with health risk?
- apple shaped: central or visceral-abdominal obesity (increased cardiovascular risk)
- pear shaped: gluteal-femoral obesity (lower risk)
How is peripheral energy status signalled to the brain?
- by fat-derived hormone leptin
- somewhat insulin
What gut-derived factors influence appetite behaviour?
- ghrelin
- peptide YY
- glucagon-like peptide 1
- cholecystokinin
How does the brain and liver impact appetite regulation?
- brain cannot metabolize fatty acids (detect only glucose levels)
- signal to brain via vagus nerve
- liver metabolizes glucose and fatty acids
What is leptin? What does it do? How?
- cytokine like hormone secreted by adipose tissue
- decreases food intake and increases metabolic rate
- primariy by inhibiting neuropeptide Y secreting neurons in arcuate nucleus of hypothalamus
What are the Ob and Rb mice?
- Ob gene: mutation that prevents production of leptin
- Rb gene: mutation of leptin receptor
- mice have obesity and low metabolic rates
What is often found in people with obesity?
- insulin resistance
- with respec to visceral adiposity
What do visceral adipose cells produce?
- significant amounts of proinflammatory cytokines
What do proinflammatory cytokines do?
- disrupt normal insulin action in fat and muscle cells
- may be a major factor in causing the whole-body insulin resistance in patients with visceral adiposity
The hypothalamus receives signals from brainstem to ARC where neurons release?
- orexigenic neurotransmitters: NPY and AgRP (activate appetite, activated by ghrelin)
- anorexigenic neurotransmitters: POMC and CART (inhibit appetite, activated y CCK, PYY, GLP-1, leptin)
What is NPY?
- neuropeptide Y
- orexigenic substance
- most powerful appetite enhancer
- co-expressed with AgRP
- both released by negative energy balance (low leptin, hypoglycemia)
What is AgRP?
- agouti-related peptide
- orexigenic substance
- high levels in obesity
What is POMC?
- proopiomelanicortin
- anorexigenic substance
- melanocortins decrease food intake
- mutations in R = obesity, hyperphagia, hyperinsulinemia
What is CART?
- cocaine and amphetamine-regulated transcript
- anrexigenic substance
- colocalized with POMC neurons
- role in decrease food intake complex
What is CCK?
- cholecystokinin
- release from gut when nutrients in lumen
- CCK-1R on vagus nerve - indicates fullness
- infusion of CCK3 - decrease meal size
What is PYY?
- peptide YY
- released from L-cells
- correlates with ingested calories
- infusion = decrease food intake and increase intervals between meals
- deficiency seen in obesity
What is GLP-1?
- glucagon-like peptide-1
- infusion decreases food intake and body weight
- agonist extendin 4
What does leptin inhibit and stimulate?
- inhibits food intake, decreases appetite
- inhibits NPY and AgRP neurons
- stimulates POMC and CART neurons
What are some features of the leptin receptor?
- belongs to the cytokine R family, signals through STAT3
- 6 subtypes
- found in hypothalamus arcuate nucleus
How are obesity and leptin linked?
- most obese people are insensitive to leptin
- mutations in leptin gene (Ob) or its receptor (Rb)
Where is ghrelin produced? How does it’s level fluctuate?
- produced in oxyntic glands of stomach
- circulating levels increase before and decrease after a meal
What does ghrelin stimulate?
- stimulates appetite: by stimulating NPY and AgRP and inhibiting POMC neurons
- stimulates release of GH
What is the receptor of ghrelin?
- growth hormone secretagogue receptor
- found in hypothalamus and pituitary
What are the circulating levels of ghrelin like in anorexic patients? Obesity?
- anorexic: levels elevated
- obesity: levels low
What is obestatin?
- from proghrelin precursor
- decrease food intake
- possible treatment for obesity
In addition to appetite regulation, what other effects does leptin have?
- decrease intracellular lipid in muscle and liver
- decrease insulin sensitivity and secretion
- regulate bone resorption
- low levels inhibit reproduction, thyroid thermogenesis and immune resp
What effects does adiponectin have?
- increase insulin sensitivity, fa oxidation, glucose uptake and decrease gluconeogenesis
- anti-inflammatory
- targets liver and muscle
- obesity: low concentration
What are the effects of adipocytokines?
- tumor necrosis factor and interleukin
- pro-inflammatory
- associated with insulin resistance
- increased levels in obesity
What are the effects of resistin?
- decrease insulin sensitivity
- not in humans
What other hormones are implicated with adipose as an endocrine organ?
- estradiol
- angiotensinogen
What are some of the diseases linked to obesity?
- type II diabetes
- coronary heart disease
- stroke
- some cancers
- inflammatory conditions
What three factors affect the occurrence of weight gain?
- behaviour
- genetics
- age
What kind of behaviours affect weight gain?
- diet
- physical activity
- lack of sleep (increase ghrelin, decrease leptin)
How do genetics affect weight gain?
- influences how body burns calories and stores fat
How does age affect weight gain?
- physical activity decreases
- GH (promotes lean muscle) decreases
- E2 decreases
How do excess carbohydrates affect insulin and trigylceride storage?
- cause liver to become insensitive to insulin-inhibited glycogenolysis
- hepatic glucose production, insulin increase, shifts oxidation to all carbs, leads to adipose fat storage
How does leptin resistance lead to obesity?
- triggers hyperphagia and weight gain
- primary: genetic, mutations in leptin signalling
- secondary: lack of response to high leptin levels (down reg)
- leptin resistance correlated with insulin resistance
