Physiology of appetite and weight Flashcards
Define obesity
Prevalence in England?
How does weight vary across our lifetime?
A neurobehavioural hereditary disorder heavily influenced by the environment
25%
As we go through life, there is a slight average weight gain as energy intake doesn’t equal energy expenditure
How can we measure body weight?
- BMI (kg/m2) >23 overweight
- Waist circumference
- Skin-fold thicknesses
- Bioelectrical impedance analysis
- Ethnicity specific cut-offs
How much does obesity contribute to UK mortality rates?
What are the health risks associated with obesity?
6% (30,000 deaths)
- Metabolic syndrome/ T2DM
- CVS disease
- Resp disease
- Liver disease
- Reproductive dysfunction
- Joint problems
- Psychological morbidities
- Cancer
As BMI increases, patients with >3 co-morbidities increases from 40% (@BMI<40), to 90% (@BMI>90)
What is metabolic syndrome?
A constellation of closely associated CV risk factors
- Visceral obesity (apple shape, not pear)
- Dyslipidaemia
- Hyperglycaemia
- Hypertension
- BMI >30
! Insulin resistance
Consider the pathophysiology of metabolic syndrome
How do increased free fatty acids contribute?
How do pro-inflammatory cytokines contribute?
- Lipolysis of visceral fat
gluconeogenesis –> dyslipidaemia - TNF-a, IL-6 (from overload white adipose tissue)
This leads to insulin resistance causing decreased expression of GLUT-4 and decreased TK activity of insulin receptor
What are the risk factors of T2DM?
How does its distribution vary?
Age, obesity, family history, ethnicity
- Affects rich people in poor countries and poor people in rich countries
- Higher prevalence due to ageing population, increased incidence of obesity, increased detection/diagnostics, increased survival with T2DM
What CVD is associated with obesity?
- Metabolic syndrome
- Increased blood volume and viscosity
- Increased vascular resistance
- Increased hypertension
- Increased left ventricular hypertrophy
- Increased CAD
- Increased stroke
What are the clinical signs of respiratory disease associated with obesity?
- Obstructive sleep apnoea (snore, lack of sleep)
- Hypoxia/ hypercapnia (can lead to R.HF)
- Pulmonary hypertension
- Accidents (daytime somnolence)
What GI/Liver disease is associated with obesity?
- Non-alcoholic fatty liver
- Non-alcoholic steatohepatitis (may progress to cirrhosis, portal hypertension, hepatocellular cancer)
- Gallstones
- Reflux
What percentage of cancer deaths in non-smokers are attributable to obesity?
What types of cancer in particular?
Possible mechanism?
Approximately 10% of cancer deaths in non-smokers attributable to obesity
- Breast, endometrial, oesophageal, colon, gallbladder, renal, thyroid
- Increased insulin, free IGF-1, oestrogen, adipo-cytokines, reflux
What are the risks to the reproductive system associated with obesity?
Polycystic ovarian syndrome
- causes oligomenorrhoea, hirsutism, acne, subfertility, endometrial hyperplasia, insulin resistance
Male hypogonadism
Adverse pregnancy outcomes
What can happen to your joins in obesity?
- Osteoarthritis
- Gout
What are the psychological effects of obesity?
- Depression
- Eating disorders (bulimia, binge, time calorie eating)
Consider the aetiology of obesity
What are the rare genetic syndromes that can contribute?
What other conditions could cause obesity?
How do genetics commonly contribute to obesity?
- Prader-Willi, Bardet-Biedl (these children lack satiety
- RARE: hypothyroidism; COMMON: cushings
- Polygenic
- Susceptibility genes
Heritability of weight is approximately equal to that of height
Consider the aetiology of obesity
How does the environment contribute to obesity?
Fast food- high fat/sugar diets, coca-colonisation of the developing world
Car ownership- Lack of physical activity
TV watching in children- Lack of physical activity
Link between number of people in your friendship group obese?
Consider the aetiology of obesity
What is fetal programming and how does it contribute to obesity?
Outline the life course model
Fetal programming: stimuli/insults at critical periods have persistent biological effects
- ‘stressors’ in utero: undernutrition, trace elements
- mechanism: epigenetic modification of gene expression
e.g. ‘Programmed’ HPA axis overactivity in adulthood is a causal factor for MS and increases vulnerability to CHD
LIFE COURSE MODEL
Factors operationg at every stage of life –> ‘pathway’ of risk –> worst outcome (associated with low birth weight, excessive weight gain in infancy/childhood, adult obesity)
Consider the aetiology of obesity
What role does the gut microbiome play in obesity?
- Integral to host homeostasis (absorption of nutrients, reabsorption of bile acids, fermentation of bile and bile acid metabolism)
- Influenced by diet (high fat, fibre)
- Influence disease risk (obesity, T2DM)
What hormones regulate appetite and weight?
Outline the findings of a mouse experiment regarding one of these hormones
Leptin, Insulin
- Signal % body fat –> hypothalamus: decrease food intake, increased energy expenditure
Experiment: “Oblob”
- Leptin deficient mouse and leptin-receptor mouse
- The LD mouse didnt go through puberty but both mice gained weight
- In humans, leptin is a starvation signal –> rare leptin (receptor) deficiency –> usually high [leptin] with high fat
What peptides are involved in the regulation of appetite and weight and how do they act?
Rapid acting peptides released from GI tract:
- CCK (sensation of fullness)
- Ghrelin (sensation of hunger)
- PYY (reduces appetite)- up to 12 hours
They act via the hypothalamus
At the hypothalamus (arcuate nucleus)
- Accelerator neurons
- ‘Brake neurons’
Consider non-medical treatments for obesity
Discuss the lifestyle modifications (diet) that can be adopted
Energy deficient diet (500-100kcal decrease)
- Reduced sat fats, sugars
- Smaller portion sizes and reduced snacking
- More fruit and veg
- Structured meals/ meal replacements prome increased weight loss
PROBLEMS:
- Most cant achieve a 5-10% weight loss
- Best hope is to MAINTAIN lifestyle change, requires ongoing management
- Obesogenic environment
Consider non-medical treatments for obesity
How can physical activity be incorporated in weight loss?
Exercise 7 days/week
- 30 min/day moderate-high intensity or 60 min low
- 10,000 steps/day (consider starting low and increasing in 500 step increments)
Consider non-medical treatments for obesity
What is a very low calorie diet?
What are the results of their efficacy from trials?
“starvation diet”- extremely low daily food energy consumption. …formulated, nutritionally complete, liquid meals containing 800 kilocalories or less per day.
Primary care programme, patients with T2DM (<6 years diagnosis). On diet for 3-5 months: inital total diet replacement then food reintroduction
RESULT: 24% of participants achieved 15kg weight loss in 12 months, 46% induced remission of T2DM, >10kg weight loss: 73%
Consider medical treatments for obesity
ORLISTAT
- Mechanism?
- Side effects?
- Binds and inhibits lipases in gut lumen, prevents the hydrolysis of dietary fat ubto absorbable FFA’s/glycerol –> excrete 1-3% dietary fat
- Side effects: flatulence, oily faecal discharge, diarrhoea, decreased absorption of fat soluble vitamins
Consider medical treatments for obesity
METFORMIN
- Indication in guidelines?
- Problems associated with its use?
BEST 1ST LINE AGENT FOR OBESITY AND T2DM
- All other hypoglycaemic agents and insulin cause weight gain
- Used in ‘diabetes prevention’ trials (although not licensed for this)
(RECOMMENDED by NICE for prevention of T2DM ub adults at high risk)
- Can only increase by 3/4 fold the proportion of patients who achieve 5% weight loss/annum
- WEIGHT IS REGAINED AFTER TREATMENT STOPPED
Consider medical treatments for obesity
How does the future look like for obesity pharmacological treatment?
Identify gut peptides/ neuropeptides/ their receptors potential therapeutic targets
Consider surgical treatments for obesity
What kind of treatment method is LAPAROSCOPIC ADJUSTABLE BANDING?
- restrictive only (lowers the amount of food you eat)
- inject/ withdraw saline to adjust the diameter of the band
Consider surgical treatments for obesity
How does a Roux-en-Y gastric bypass work?
Side effects?
- Restrictive
- Causes malabsorption, alterations in gut hormones ( increases satiety) and bile acid flow
- micronutrient deficiencies (supplement iron, B12, folate, Ca2+, Vit-D)
- Dumping syndrome (GI and vasomotor symptoms)
Consider surgical treatments for obesity
Advantages and disadvantages of Roux-en-Y gastric bypass?
ADVANTAGES:
- Weight loss (25-30%)
- Resolve or improve co-morbidities (cost savings)
- SOS study shows loss of weight and decreased CVD Rx
(Swedish obesity study- ongoing, non-randomised, prospective, controlled)
DISADVANTAGES:
- Perioperative mortality/ morbidity (dependent on surgeon/ procedure)
- long term follow up (micronutrient deficiencies)
- Some weight re-gain
- Expense (cost effective by 2-5 years, depending on comorbidities and weight)
What do the NICE guidelines say about bariatric surgery?
How do the NHS guidelines differ?
They were changed in 2014
- BMI > 40 (with comorbidities, first line 50)
- Recent onset T2DM
- Expedite bariatric surgery if BMI >35
NHS guidelines as per NICE but:
- Must be obese for more than 5 years
- must engage with non-surgical weight loss programme for 12-24 months
76.2% operations in NHS (the rest independently funded) with an average BMI of 48.8
Public health regimes to prevent obesity?
- Ensure kids at scholl are getting 1 mile/day, healthy school meals, no vending machines
- Marketing/media/ social media
- Food labels, food advertisement
