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Obesity Canada > 4. The science of obesity > Flashcards

4. The science of obesity Flashcards

1
Q

what are some key drivers that promote overconsumption of food?

A

The increased availability of processed, affordable and effectively marketed food, abundance of sugar-sweetened beverages,
economic growth, behavioural changes and rapid urbanization in lowand middle-income countries

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2
Q

what is the most important player in obesity?

A

brain

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3
Q

how does the hypothalamus act in obesity?

A

homeostatic area - role in energy homeostasis by regulating energy intake and expenditure

complex control of appetite

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4
Q

what is the hunger centre that controls feeding behaviours?

A

the arcuate nucleus of the hypothalamus

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5
Q

what are 2 sets of neuronal population that reside in the arcuate nucleus?

A

neurons co-expressing agouti-related protein (AgRP) and neuropeptide Y (NPY)

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6
Q

what activates AgRP/NPY
neurons in the arcuate nucleus?

A

hormonal and neural signals from the gut, adipose tissue, and the peripheral organs

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7
Q

if AgRP/NPY neurons in the arcuate nucleus get activated, what happens?

A

stimulate hunger sensation and trigger food-seeking behaviours

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8
Q

the activity of these AgRP/NPY neurons is rapidly reduced upon access to food - these neurons are primarily involved in food-seeking or the homeostatic control of appetite, but are less likely to normally drive xxx?

A

food consumption

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9
Q

how do these AgRP/NPY neurons mediate their downstream effects?

A

via the melanocortin-4 receptors located in the nearby paraventricular nucleus

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10
Q

The AgRP/NPY neurons project directly to the second set of neurons that co-expressing what?

A

pro-opiomelanocortin (POMC) and
cocaine- and amphetamine-regulated transcript (CART)

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11
Q

what do pro-opiomelanocortin (POMC) and
cocaine- and amphetamine-regulated transcript (CART)?

A

suppress food intake by firing through the downstream inhibitory Y1 and gamma-aminobutyric acid (GABA) receptors

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12
Q

The homeostatic control of appetite in the arcuate nucleus is influenced by a
number of factors including?

A

the nutritional status of the organism, nutrient
sensing and availability, taste, smell and food preferences.

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13
Q

what is hedonic eating?

A

neural systems that involve emotional, pleasurable and rewarding aspects of eating

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14
Q

Hedonic eating is based on the feelings of reward
and pleasure that are associated with …?

A

seeing, smelling or eating food

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15
Q

in hedonic eating, the signals are transmitted by which pathways?

A

dopaminergic, opioid and endocannabinoid pathways

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16
Q

what does dopamine signal in response to emotional triggers, such as sadness, or environmental triggers, such as the smell or sight of delicious food?

A

desire to eat

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17
Q

when are Opioid and endocannabinoid
signals released ?

A

when food is consumed, and are responsible for
the feeling of pleasure associated with eating

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18
Q

Some people living
with obesity may have a heightened anticipation (wanting) of the
pleasure of food driven by a dysregulation of which?

A

dopamine

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19
Q

what is dysfunctional and is downgraded compared to the anticipation, resulting in a need to overeat to achieve the level of the anticipation?

A

the pleasure of eating the food (liking)

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20
Q

what is the target for the treatment of obesity?

A

controlling dysregulation between wanting and liking of eating

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21
Q

where is a brain region that is tied to consummatory behaviours and mediates positive reinforcement?

A

lateral hypothalamus

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22
Q

Hedonic eating is also
controlled by which system?

A

corticolimbic system, which consists of cortical areas, basal ganglia, hippocampus and amygdala in the midbrain.

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23
Q

which is responsible for executive functioning and overriding primal behaviours driven by the mesolimbic system

A

cognitive lobe

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24
Q

Cognitive functioning works well under optimal conditions including.. which help to deal with adverse situations

A

rest, oxygen, decreased stress and supports

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25
Q

excessive eating often occurs in the evening - why?

A

suboptimal conditions, following the accumulation of
stressors throughout the day, fatigue and lower levels of will power

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26
Q

There are also other areas of executive dysfunction in some people
living with obesity, primarily in ..?

A

decision making,
response inhibition
and cognitive flexibility

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27
Q

Current research indicates that there is significant crosstalk between
homeostatic and hedonic eating, which is mediated by many of what signals?

A

endocrine and gut-derived signals

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28
Q

which act on the dopaminergic neurons in the midbrain to modulate food reward and hedonic eating?

A

Leptin, insulin, ghrelin, glucagon-like peptide-1 (GLP-1)

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29
Q

what is another appetite-suppressing network?

A

calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN)

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30
Q

what does calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) suppress?

A

eating

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31
Q

when are PBN-CGRP neurons activated and what signal do they provide?

A

when food intake;
signal of satiety

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32
Q

what is actively involved in the alignment of fasting and feeding
with the sleep/awake cycle?

A

the hypothalamic circadian clock network

33
Q

how does the hypothalamic circadian clock network work?

A

the AgRP neurons coordinate the leptin response and glucose metabolism with arousal

34
Q

what does Cognitive areas in the prefrontal cortex execute?

A

control on the decision to eat and the food choices

35
Q

what are two key hormones that communicate to the homeostatic control of the long-term energy reserve and nutritional status in the body?

A

Leptin and insulin

36
Q

what is a fat-derived hormone that is secreted by white adipose tissue in proportion to the body’s fat mass?

A

Leptin

37
Q

Leptin and insulin bind to their respective receptors in the arcuate nucleus to do what?

A

decrease food intake and increase energy expenditure

38
Q

In states of decreasing body fat stores, circulating leptin levels fall and
signals what?

A

the hypothalamus to inactivate the POMC/CART-expressing
neurons to promote feeding;

while simultaneously lowering its inhibitory effect on the AgRP/NPY-expressing neurons to increase appetite
and decrease energy expenditure

39
Q

As adiposity increases, leptin levels
increase in the circulation and exert negative feedback to …

A

suppress
appetite to prevent further weight gain

40
Q

leptin resistance
also occurs in which people?

A

who have excessive adiposity

41
Q

what are potent anorexigenic gut hormones that are secreted by enteroendocrine L-cells in the small bowel in response to food ingestion?

A

GLP1 - powerful incretin;
peptide YY3-36 (PYY) - delays gastric emptying

42
Q

how are GLP1 and PYY working against obesity?

A

promote satiation (meal termination) and satiety by activating the POMC/PYY neurons while reducing hunger via the AgRP/NPY neurons

43
Q

what is another peptide secreted concurrently with GLP-1 and PYY?

A

Oxyntomodulin - enhances satiety and decreases food consumption

44
Q

when is CCK secreted and what does it do?

A

in response to fat and protein ingestion;
stimulates gall bladder contractility and pancreatic enzyme secretion, and slows gastric emptying;

mediates fat and protein satiation as well as glucose-regulatory effects on the hypothalamus, and also via the vagal afferent fibres

45
Q

what is pancreatic polypeptide (PP)?

A

secreted by F-cells in the pancreatic islets;

released during the postprandial phase to enhance satiety

46
Q

what is an orexigenic hormone produced in the gastric fundus which increases hunger and stimulates food intake?

A

ghrelin

47
Q

Upon food ingestion, sensory information on the volume and
composition of the meals, and notably satiation, is relayed to where?

A

nucleus tract solitarius (NTS) in the brainstem by the vagal afferent fibres

48
Q

what does NTS in the brainstem do when they have information?

A

integrates and transmits the signals to the homeostatic control pathways in the hypothalamus, primarily influencing satiety and meal termination

49
Q

how many genetic regions are now known to influence obesity traits?

A

more than 140

50
Q

what are examples of mutations in genes involved in appetite control?

A

5 Loss of function mutations in leptin, leptin receptor,
pro-opiomelanocortin and melanocortin receptor-4

51
Q

6 Eleven monogenic forms of obesity have been discovered. They are rare, and the most common cause is what?

A

heterozygous mutation in MC4R - 2-5% of severe obesity in kids

52
Q

what are endocrine causes of obesity ?

A

Cushing disease;
hypothyroidism;
pseudohypoparathyroidism;

  • 1% of all cases of obesity
53
Q

what do syndromic forms of obesity include?

A

Prader-Willi, Bardet-Biedl and Cohen syndromes

54
Q

Leptin binds to specific receptors, which belong to …?

A

the interleukin-6 receptor family of class I cytokine receptors

55
Q

Leptin’s effect is
not limited to appetite regulation and energy homeostasis; it also
exerts a wide array of…?

A

endocrine and metabolic influences

56
Q

which suppresses insulin secretion from pancreatic β cells and plays a role in insulin resistance?

A

Leptin

57
Q

which hormone is abundantly produced by adipocytes, and exerts pleiotropic effects on a broad array of physiological processes, including energy homeostasis, vascular function, systemic
inflammation and cell growth?

A

Adiponectin

58
Q

what is adiponectin’s most important function in obesity?

A

an insulin-sensitizing agent which stimulates insulin gene expression and secretion

59
Q

Adiponectin levels are inversely correlated in xxxx
and xxxx, and reflect xxxx

A

Adiponectin levels are inversely
correlated in obesity and insulin-resistant states, and reflect wholebody insulin sensitivity

60
Q

Circulating adiponectin levels are lower in
people with …

A

obesity, polycystic ovarian syndrome, individuals with
impaired glucose tolerance or type 2 diabetes.

61
Q

Decreased adiponectin
level, or hypoadiponectinemia, is associated with increased risk for …

A

developing type 2 diabetes in otherwise healthy people

62
Q

in which condition can adipose tissue dysfunction may develop?

A

continuous positive energy balance in people with an impaired expandability of subcutaneous adipose tissue

63
Q

The inability to store excess
calories in healthy subcutaneous fat depots can lead to increased
visceral fat accretion and ectopic fat deposition in which organs?

A

liver, muscle, epicardium of the heart

64
Q

Adipose tissue expansion often leads
to dysfunctional changes, which are characterized by …?

A

inflammation,
inappropriate extracellular matrix remodelling and insufficient angiogenic potential.

65
Q

what is thought to be the driver for
adipose tissue dysfunction?

A

cellular hypoxia

66
Q

A consequence of dysfunctional adipose tissue, especially in the visceral depots, is augmented production of what?

A

fat-derived proinflammatory cytokines, or adipokines

67
Q

what are adipokines?

A

tumour necrosis factor-α, interleukins,
C-reactive protein and monocyte chemotactic protein-1

68
Q

what can adipokines accelerate the progression to?

A

fibrosis,
accelerated angiogenesis,
apoptosis and autophagy by promoting the migration of immune cells into adipose tissue

69
Q

dysfunctional adipose tissue
can lead to the development and progression of ..?

A

a myriad of adiposity-related comorbidities, such as type 2 diabetes, hypertension,
dyslipidemia, nonalcoholic fatty liver disease, cardiometabolic risks
and atherosclerotic cardiovascular disease.

70
Q

what is brown adipose tissue involved in?

A

whole-body energy homeostasis through non-shivering thermogenesis

71
Q

Recruitment of beige adipocytes, or
“beiging” of white fat, can be induced by ..

A

chronic exposure to cold
temperatures and, to some extent, exercise

72
Q

what are Beige adipocytes?

A

inducible forms of thermogenic adipocytes

73
Q

Recent data suggest that gut microbiota
may influence weight gain and insulin resistance through different
pathways, including ?

A

energy harvesting from bacterial fermentation,
short-chain fatty acid signalling and bile acid metabolism

74
Q

Human studies have indicated that the
primary bacteria involved in weight homeostasis are?

A

firmicutes - promote weight gain;

bacterioidetes - more in lean individuals

75
Q

The predominant theory between
the link of obesity and cardiometabolic risk is described as obesity
inducing an insulin resistant state through two primary mechanisms - which are?

A

defective insulin signal, and chronic tissue inflammation
and increased adipose tissue macrophages

76
Q

Adipose tissue is a
source of increased levels of which?

A

circulating free fatty acids due to increased lipolysis

77
Q

In the liver, increased free fatty acid flux results in ?

A

increased glucose production, triglyceride synthesis and secretion
of very low-density lipoprotein

78
Q
A

Obesity Canada (13 decks)

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