Obesity Flashcards
Obesity
Abnormal or excessive fat accumulation sufficient to adversely affect health + reduce life expectancy
Obese BMI
30 +
Morbidly obese BMI
40 +
Girls with obesity 1975 –> 2016
5 million –> 50 million
Boys with obesity 1975 –> 2016
6 million –> 74 million
EU average obesity
14%
% of population 16+ with BMI 30 or greater
Obesity Tower Hamlets children starting primary school
1 in 8
Obesity Tower Hamlets children leaving primary school at 11
1 in 4
Tower hamlets borough child obesity
5th highest London
6th highest in country
Chicken shop mile
197 hot food takeaways
Average of 42 junk food outlets PER SCHOOL
Tower hamlets worst areas compared to England
Deprivation
Children under 16 in poverty
Obese children in yr 6
Food deserts (limited food options) in US associated with..
Increase in obesity + diabetes
Obesogenic environment
Increased food intake
Less exercise
Food industry more interested in profit than public health
Medications + weight issues
10-15% weight issues linked to medication Mood stabilisers Diabetes Medicines Corticosteroids Beta blockers Allergy relievers Drugs that prevent seizures + migraines
Insulin + weight gain
Inhibits breakdown + release from fat cells
Decreases rate of lipolysis in adipose tissue (lowers plasma FA level)
Stimulates FA and triacylglycerol synthesis in tissues
Increases uptake of triglycerides from blood into adipose tissue
Decreases rate of FA oxidation in muscle + liver
Lipohypertrophy
Enlargement of fat cells local to where insulin is injected
T2D drugs that increase insulin and weight
Insulin
Sulfonylureas (Glyburide, Glicizide)
TZD
T2D drugs that don’t affect insulin and weight
Metformin
DPP IV inhibitors (Januvia, Onglyza, Trajenta)
T2D drugs that decrease insulin and weight
SGLT-2 inhibitor
Acarbose
Heritability for obesity
High (typically 70%)
Thrifty gene hypothesis
Genes that predispose to obesity would have had a selective advantage in populations that frequently experience starvation
–> ppl that have these genes now in obesogenic environment might be those that overreact –> extremely obese, not just slightly overweight
Thrifty gene hypothesis support
Many genes in glucose + lipid metabolism subject to positive selection in last 10,000 years
–> especially Asian + African ethnic groups
CREBRF variant?
Syndrome monogenic obesity
Exceptionally rare
Characterised by mental retardation, dysmorphic features + organ specific abnormalities
–> in ADDITION to obesity
Prader-Willi syndrome
SNRPN gene
Autosomal dominant
Short physique
Hypotonia + hypogonadism
Fragile X syndrome
FMR1 gene
Autosomal dominant
Psychological + speech defect
Macro-orchidism
Bardet-Biedl + Alstrom syndrome
Ciliopathy
The primary cilium has key role in differentiation of adipocytes –> pathogenesis of obesity is in part attributed to defect in adipogenesis
Cilia mediated leptin receptor (LEPR) signalling
Non-syndromic monogenic obesity
Currently 12 genes have been identified that have roles in energy maintenance as part of leptin-melanocortin pathway
LEP, LEPR, BDNF etc
Non- syndromic
Single gene disorder that leads to a highly penetrant form of obesity
Adipocyte differentiation- obesity
Ciliopathies- primary cilia dysfunction
Mutations in Peroxisome-proliferator-activated receptor gamma 2 (PPARgamma2)
–> transcription factor that has key role in adipocyte differentiation
Peroxisome-proliferator-activated receptor gamma 2
Transcription factor
Key role in adipocyte differentiation
Targeted by TZD drugs
Polygenic obesity
227 genetic variants involved in different biological pathways have been identified CNS food sensing + digestion adipocyte differentiation insulin signalling lipid metabolism muscle + liver biology gut microbiota
Epigenetic variation
Environmental + nutritional influences during critical periods in development (particularly gestation) can have permanent effects on an individual’s predisposition to obesity
Adipose tissue
Bonafide endocrine organ
Defects can originate in the tissue itself, or its ability to communicate to the brain or the brain response itself, or the downstream effectors, or a combination
Apple shape
More visceral fat
higher risk weight-related health problem
Pear shape
Less visceral fat
Lower risk of weight-related health problem
Lifespan
Obesity-related diseases could cut lifespan by 11 years
Obesity as a risk factor
CV diseases Pulmonary diseases Metabolic diseases Osteoarticular disease Cancer Psychiatric illness
Childhood obesity
Associated with early onset type 2 diabetes + increased mortality risk of CHD in adulthood
Obesity + T2D
Chronic inflammation
Altered adipokine levels (high leptin)
Breakdown of fat metabolism (accumulation lipids in tissues)
Breakdown of regulation of glucose metabolism
Non alcoholic fatty liver disease
Build up of fat in liver
Overweight/obese
Associated with high cholesterol/high BP/T2D
5% UK population
Orlistat
Gastric and pancreatic lipase inhibitor
Reduces absorption of dietary fat–> doesn’t allow lipase to attach to fat + break it down into absorbable size
Surgery
First do weight management course Laparoscopically Morbid obesity BMI>35 AND obesity related complications --> only after conventional medical treatments have failed
Surgery procedures- restrictive procedures
Restrict ability
Band restricts food passage
Removal of part of stomach
Surgery procedures- malabsorptive procedures
Reduce ability to absorb nutrients
Can cause nutrient deficiencies, malnutrition, and in some cases anastomotic leaks + dumping syndrome (rapid gastric emptying)
Malabsorptive procedures examples
Biliopancreatic diversion
Roux-en-Y gastric bypass
Restrictive procedures example
Adjustable gastric banding
Vertical banded gastroplasty
Sleeve gastroplasty
Restrictive plus malabsorptive procedures
Dudoenal switch
Roux-en-Y gastric bypass
Intragastric balloon
