Obesity Related Pathogenesis In The Short And Long Term

Question 1

How obesity is defined and assessed

Answer 1

• definition: a complex, incompletely understood, serious and chronic disease which was part of a cluster of non-communicable diseases that required prevention and management strategies at both individual and societial level
• WHO definition: the disease in which excess body fat has accumulated to such an extent that health may be adversely affected
• diagnosed via BMI over 30, class 1 (30-34.9) class 2 (35-39.9), class 3 (>40). BMI for asians is 2.5 points lower
• waist circumference used if BMI <40
• waist/hip ratio
• body composition analysis: BIA, DEXA, MRI
• scoring system to prioritise the greatest health risk and monitor health improvement: edmonton obesity staging system (EOSS)

Question 2

The impact of obesity on health and life expectancy

Answer 2

• adipocytes enlarge and multiply and are biologically active secreting adipokines and proinflammatory cytokines: leptin, TNFa, IL6, decrease in adiponectin
• metabolic risks: asthma, fatty liver, gallstones, infertility, cancers, CVD, T2DM
• mechanical risks: reduced physical functioning, incontinence, joint diseases, sleep apnea, chronic back pain
• CNS risks: depression and anxiety
• prevalence of complications (including cancers) increases with BMI
• a BMI >40 is a high risk group for COVID
• life expectancy decreases as BMI increases: normal BMI chance of getting to 70 (80%), BMI of 35-40 60% chance, BMI of 40-50 ~50% chance
• EOSS can be used to assess those at an increased risk of dying, as it includes comorbidities and severity

Question 3

How is body weight regulated?

Answer 3

• Satiety: POMC neurons in arcuate nucleus are activated by neuropeptides such as PYY which activates MC3/4R neurons in the hypothalamus which decreases appetite. Leptin and insulin should decrease appetite too
• hunger: ghrelin release activates NPY/AgRP in the arcuate nucleus which activates Y1/Y5R in the hypothalamus causing increased appetite
• there is cross talk between the hypothalamus and the brainstem which can also lead to feeding, gastric emptying and metabolic rate
• if obese very early in life may have leptin deficiency, but most obese people have high levels of circulating leptin but are just resistant to effects

Question 4

Genetic predisposition and obesity

Answer 4

• in early life if obese may have leptin deficiency or mutation in the POMC axis but this is very rare
• body weight is highly heritable: 40-70%
• obesity risk FTO variant (SNP rs9939609) have stronger responses to food from reward systems in brain, decreased satiety, get hungry quicker after eating and have higher levels of circulating ghrelin

Question 5

Roles of lifestyle and other causal factors in development of obesity

Answer 5

• people not as active as before
• can overlay takeaway maps with obesity: chances of being obese increased if neighbourhood fast food
• psychosocial factors: feelings of isolation, abuse

Question 6

Role of gut hormones in regulating energy balance

Answer 6

• PYY (satiety) is released from gut along with ghrelin (hunger)
• if infuse patients with PYY have lower energy intake at ad libitum meal
• obese individuals have lower PYY
• PYY acts upon brain in centers that respond to eating and reward
• obese people have higher ghrelin levels
• all GI hormones have peripheral effect and act on many areas including taste

Question 7

Treatment options for obesity

Answer 7

• if lose >15% body weight highly likely to achieve remission of many obesity related chronic diseases
• diet and lifestyle changes and behavioural therapy given to all BMI over 25
• pharmacotherapy (such as orlistat) can be to those >30 BMI or >27 if additional comorbidities
• bariatric surgery offered for those >40 BMI or >35 with comorbidites
• bariatric surgery is associated with sustained weight loss and improves survival with immediate effects (ie remission from diabetes on the same day) due to changes in gut hormone axis. 25% weight loss at 5 years. 40% reduction in mortality from comorbidites

Question 8

How does bariatric surgery cause weight loss

Answer 8

• favourable gut hormone profile
• reduced hunger/appetite
• reduced preference for sweet/fat
• reduced reward value for food and correction of brain response to food cues
• improved gut microbiome
• restoration of insulin and leptin sensitivity

Question 9

Why is weight loss through dieting difficult?

Answer 9

• activates powerful compensatory pathways
• increased hunger and interest in food, reduced energy expenditure
• increased ghrelin reduced PYY
• homeostatic reward system increases in response to food

Question 10

Why obesity is recognised as a chronic disease?

Answer 10

• multi-factorial disease with many contributory factors
• increased adipose tissue increasing inflammatory cytokines
• pancreas dysfunction
• gut hormone dysfunction
• genetic susceptibility
• medications