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PT4023 CA2 > L15 Obesity & Appetite > Flashcards

L15 Obesity & Appetite Flashcards

1
Q

What is obesity?

A

Obesity is an illness where health is adversely affected by excess body fat. Obesity occurs when the homeostatic mechanisms controlling energy balance become disordered or overwhelmed.

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2
Q

What are the dangers of obesity?

A

Hypertension, hyperlipidemia, T2DM + obesity = metabolic syndrome
Obesity increases the risk of cardiovascular conditions (e.g. MI), strokes, cancer, respiratory disorders, digestive problems, osteoarthritis

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3
Q

Factors that have led to the global obesity epidemic

A

sedentary lifestyle, genetic susceptibility, cultural influences, unrestricted access to plenty of calorie dense foods

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4
Q

Hormones involved in the regulation of appetite and body weight

A

CCK, amylin, insulin, glucagon, PYY3-36, GLP-1, oxyntomodulin, leptin, ghrelin

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5
Q

Role of leptin

A

decreases the desire to take in food - longer-term regulation of food intake and body weight

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6
Q

Why does leptin not have the same effect in obese individuals?

A

The majority of obese individuals are leptin-resistant, and the leptin binding to receptors does not have the effect that it should have. Therefore, the effect of reduced desire to take in food is not elicited in obese individuals.

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7
Q

Role of ghrelin

A

increases food intake by increasing the size and number of meals (i.e. makes you hungrier)

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8
Q

Leptin is controlled by…

A

the amount of adipose tissue

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9
Q

Leptin synthesis is increased by…

A

glucocorticoids, insulin, oestrogens

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10
Q

Leptin synthesis is decreased by…

A

beta-adrenoceptor agonists

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11
Q

What peptide acts centrally to produce an anorexigenic effect by modulating neuropeptides in the hypothalamic circuits?

A

Nesfatin1

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12
Q

Areas of the brain that regulate appetite, feeding behaviour and energy status

A

hypothalamus (main), nucleus accumbens, amygdala, nucleus tractus solitarius

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13
Q

Role of arcuate nucleus (in hypothalamus) in appetite

A
  • receives inputs from GIT and contains receptors for leptin & other hormones
  • has extensive reciprocal connections with other parts of the hypothalamus involved in monitoring energy status (PVN & VMH in particular)
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14
Q

2 groups of functionally distinct neurons in arcuate nucleus

A
  1. Anorexigenic (appetite suppressing) neurons: secrete POMC- & CART-derived peptides
  2. Orexigenic (appetite-promoting) neurons: secrete neuropeptide Y & agouti-related peptide
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15
Q

What has a stimulatory effect on anorexigenic neurons, and an inhibitory effect on orexigenic neurons?

A

Insulin, leptin and CCK (limit the size of the meal)

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16
Q

What endocannabinoids are involved in the hedonic aspects of eating?

A

anandamide and 2-arachidonyl glycerol

17
Q

Factors involved in the regulation of energy balance that are suggested to be involved in obesity

A
  • Genetics
  • Leptin resistance
  • TNF alpha (relays info from adipose tissue to brain)
  • Alterations in nuclear receptors e.g. PPAR (promote formation of adipose tissue)
18
Q

Targets of drugs used to treat obesity

A
  1. GIT - lower nutrient absorption
  2. CNS - reduce food intake by decreasing appetite or increasing satiety
19
Q

Anti-obesity drugs withdrawn due to adverse effects

A
  1. Dinitrophenol (DNP): blocks mitochondrial ATP production - diverts energy metabolism to generate heat instead of ATP (increases overall metabolic rate). Can cause life-threatening hyperthermia
  2. 5-HT2 agonists (cause pulmonary hypertension & cardiac valve defects)
    - Dexfenfluramine or combined with phentermine (Dex-Phen)
    - Fenfluramine or combined with phentermine (Fen-Phen)
20
Q

Withdrawn centrally-acting appetite suppressants

A
  1. Sibutramine (cardiovascular risk): inhibits reuptake of 5-HT & NA at the hypothalamic sites that regulate food intake - weight loss, increased satiety, decreased plasma TGs & LDL, increased HDL
  2. Lorcaserin (cancer risk, patients regained weight after stopping): 5-HT2c receptor agonist - suppresses appetite, increases POMC levels in hypothalamus
21
Q

How do amphetamines affect appetite?

A

Amphetamines are CNS appetite suppressants. However, they are generally helpful only during the first few weeks of therapy. Associated with significant toxicity, hypertension and addiction.

22
Q

Currently approved centrally-acting appetite suppressants

A
  1. Qsymia: mix of phentermine (stimulates synaptic release of 5-HT, NA & DA) & topiramate (anticonvulsant, increases GABA activity)
    - suppresses appetite through anorexigenic POMC
    - FDA requires REMS for Qsymia because topiramate is teratogenic
  2. Contrave: mix of naltrexone (opioid receptor antagonist) & bupropion (NDRI, increases activity of anorexigenic neurons)
23
Q

What is Orlistat and how does it work?

A
  • synthetic derivative of endogenous lipase inhibitor lipstatin
  • currently approved for treatment of obesity
  • reacts with serine residues at active sites of gastric & pancreatic lipases - irreversible enzyme inhibition
  • prevents breakdown of dietary fat to FAs & glycerol - 30% of dietary fat excreted in faeces
  • some of the adverse effects also lead to reduced food intake (good safety profile)
24
Q

How is Orlistat administered?

A

Given orally immediately before, during or 1 hour after each main meal, up to 3 times daily

25
Q

Unwanted effects of Orlistat

A

abd cramps, flatus with discharge, faecal incontinence, intestinal borborygmi, oily spotting, absorption of certain drugs & fat-soluble vitamins may be affected (e.g. OCP, cyclosporin)

26
Q

Glucagon-like peptide-1 analogues used to treat obesity

A
  1. Liraglutide: approved for treatment of obesity & T2DM. Increases satiety & suppresses appetite through hypothalamic pathways
  2. Semaglutide: approved for use in treatment of obesity in 2021. March 2022: approved for use in Europe as ‘Wegovy’
27
Q

What long-acting amylin analogue has resulted in significant weight loss and has been well-tolerated in clinical trials?

A

Cagrilintide - induces a feeling of fullness

28
Q

Over the counter drugs for obesity

A
  1. Clavitanol (IQP-VV-102):
    - Reduces calorie intake from carbs, sugars & fats
    - Contains L-arabinose (inhibits intestinal absorption of glucose, reduces lipogenesis & TG conc in liver)
    - Contains Grape marc extract (inhibits α-amylase & α-glucosidase - reduces carb digestion & absorption)
  2. Litramine (IQP-G002AS):
    - Dietary fibre derived from cactus plant that binds fat (prevents absorption of fat, increases excretion in faeces)

PT4023 CA2 (6 decks)

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