HMB204 - Lecture 1 - The Obesity Epidemic

in the early 20th century, what was health considered to be?

-it was considered to be the absence of disease

in 1947, what did WHO (world health organization) redefine health as?

-they defined it as: a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity

infirmity

-physical or mental weakness

what factors can affect someone’s health?

-lifestyle

-social backgrounds

-work

-living environment

-education

-diet

-economic status

what are the 12 determinants of health?

1. income and social status

2. social support networks

3. education and literacy

4. employment/working conditions

5. social environments

6. physical environments

7. personal health practices & coping skills

8. healthy child development

9. biology and genetic endowment

10. health services

11. gender

12. culture

what is helping us (humans) live longer (increased life expectancy)? (7)

• improved life settings

• public health & medical advances

• reduced childhood mortality (vaccines & sanitation)

• antibiotics

• improved living standards

• sufficient food (more)

• healthier lifestyles

what is killing humans?

-communicable and non-communicable diseases such as ischaemic heart disease, COVID-19, stroke, chronic obstructive pulmonary disease, lower respiratory infections etc.

communicable disease

-an illness caused by pathogens (viruses, bacteria, fungi, parasites) that can be transmitted (ex. person to person, person to animal)

noncommunicable disease

-chronic diseases that cannot be transmitted and are long-term. They result from genetic, physiological, environmental, and behavioural factors (ex. type 2 diabetes)

which of the leading causes of death are health consequences of obesity? (4)

1. ischaemic heart disease

2. stroke

3. diabetes mellitus

4. kidney disease

what was the obesity prevalence trend amongst adults in Canada?

-all groups showed a significantly increasing trend (p < 0.001)

epidemic

-widespread occurrence of disease that spreads quickly and affects many individuals at the same time (ex. HIV, AIDS)

obesity

-is a chronic and multifactorial disease characterized by excessive body fat accumulation that significantly impairs health

-not only due to excessive calorie intake

-involves interactions between genetic, environmental, behavioural, and metabolic factors

-most common definition of this is based on the Body Mass Index (BMI)

-changes how our cells are communicating with one another

-more than 1 billion people were living with this in 2022

-this among adults has more than doubled since 1990 and quadrupled in children and adolescents (5-19 yo)

-can create changes in the cellular composition of fat pads and the modulation of cell phenotypes

what does BMI stand for and what is its equation?

-body mass index

-this fails to capture the various risks associated with different forms of fat distribution

→ BMI (kg/m²) = weight in kilograms /height in metres²

cachexia

-underweight

• <18.5 (kg/m²)

-increased risk of health problems

normal weight

-least risk of health problems

• 18.5 to 24.9 (kg/m²)

overweight

-increased risk of health problems

-excess body fat but not as bad

• 25.0 to 29.9 (kg/m²)

obese

-is a BMI >30.0 (kg/m²)

class 1 obese

-is 30.0 to 24.9 (kg/m²)

-high risk of health problems

class 2 obese

-is 35.0 to 39.9

-very high risk of health problems

class 3 obese

-is >40.0

-extremely high risk of health problems

what are the 2 types of fat distribution?

1. android (apple) fat distribution

2. gynoid (pear) fat distribution

android (apple) fat distribution

-fat accumulates in the abdomen

-high proportion of visceral fat

-higher metabolic disease risk (heart disease, diabetes)

-metabolic syndrome risk

-at greater risk of having cardiovascular disease etc.

-common in men

gynoid (pear) fat distribution

-fat accumulates in hips/thighs

-high proportion of subcutaneous fat

-lower metabolic disease risk

-harder to lose and linked to joint issues

-common in women

visceral fat

-fat that surrounds the organs

-also known as adiposity

subcutaneous fat

-fat under the skin

-fat you can pinch

what are the 3 other classification systems for obesity?

1. skinfold measurement

2. waist circumference

3. DEXA scans (dual-energy X-ray absorptiometry scans)

skinfold measurement

-callipers used to measure the thickness of subcutaneous fat at specific body sites (abdomen, thigh, triceps)

-questionable accuracy

-not the best way to classify obesity

waist circumference

-measures central adiposity (visceral fat)

-circumference > 40 inches for men and > 35 inches for women indicate higher risk for obesity-related health issues (know these values**)

DEXA scans

-dual-energy X-ray absorptiometry scans

-can have clothes on for this scan

-highly accurate, non-invasive

-two low-dose X-rays collected at different energy levels – one absorbed by soft tissue and one by bone

-provides a detailed breakdown of body composition (fat mass, lean muscle mass, bone mineral density) and regional fat distribution (visceral and subcutaneous)

what is understanding obesity more than?

-understanding obesity is more than just understanding weight distribution and fat content

adipose tissue

-body fat

-is a loose connective tissue composed of adipocytes

-found in both subcutaneous and visceral fat

-major organ in the endocrine system that produces hormones (leptin, estrogen, resistin) and cytokines

adipocytes

-fat cells

-undergo hypertrophy as obesity develops

what are the 2 types of adipose tissue?

1. white adipose tissue (WAT)

2. brown adipose tissue (BAT)

white adipose tissue (WAT)

-stores energy

-most abundant (visceral & subcutaneous fat)

-single lipid droplet (unilocular) and a few cellular organelles

-provides energy storage (where fats get stored), insulation, and cushioning

-secretes adipokines that regulate energy balance, hunger, and satiety

-drug focus: remodel, reduce, inflammation, promote browning

-pathological concerns: fibrosis, inflammation, insulin resistance

brown adipose tissue

-generates body heat

-only occurs when we are babies

-present in infancy and diminishes with age

-contain multiple lipid droplets (multilocular) and cellular organelles (mitochondria)

-heat generation through non-shivering thermogenesis (what keeps babies from going hypothermic)

-drug focus: activate or expand

-mitochondria containing thermogenin, aka uncoupling protein-1 (UCP1)

non-shivering thermogenesis

-heat production without muscle contractions

-converts excess calories to heat

thermogenin

-also known as uncoupling protein-1 (UCP1)

-dissipates the mitochondrial protein gradient as heat via oxidation

multilocular

-a structure, often a cyst or tumor, divided into multiple compartments or “locules” by internal walls (septa)

unilocular

-having a single compartment, chamber, or locule

-a structure that has just one internal space without septa (walls) or solid components

adipokines

-different hormones and signaling molecules

-anti-inflammatory types of these are produced by lean tissue

what are signaling proteins?

-hormones and cytokines

what are 2 types of signaling proteins?

1. leptin

2. adiponectic

leptin

-for appetite control

adiponectin

-promotes anti-inflammatory

-insulin sensitizer

-inhibits macrophage-derived TNF

-comes from adipocytes

-produced by lean tissue

-reduced during conditions of obesity

what impacts adipokine regulation?

-intracellular communication does

what are the components of WAT under conditions of obesity?

1. TNF

2. WNT5a

3. adiponectin

4. SFRP5

what happens to the components of WAT under conditions of obesity?

• macrophage-derived TNF and WNT5a are upregulated

• adipocyte-derived adiponectin and SFRP5 are downregulated

• promotes type 2 diabetes

SFRP5

-inhibits macrophage-derived WNT5a

-comes from adipocytes

-promotes anti-inflammatory

-produced by lean tissue

-reduced during conditions of obesity

-suppression of pro-inflammatory WNT signaling

WNT5a

-comes from macrophage

-inhibits SFRP5

-promotes inflammatory

-increased during conditions of obesity

-produced in states of obesity

TNF

-comes from macrophage

-inhibits adiponectin

-promotes inflammatory

-increases during conditions of obesity

-antagonism of insulin signaling

-produced in states of obesity

what do the classifications of adipose tissue depend on?

-they depend on the person’s weight

what are anti-inflammatory adipokines produced by?

-they are produced by lean tissue

what are pro-inflammatory factors produced in?

-they are produced in states of obesity

what does obesity with metabolic dysfunction promote?

-it promotes adipocyte necrosis and lowers vascular function

necrosis

-uncontrolled cell death

what are the conditions of inflammation, metabolic control and vascular function and structure of AT in lean individuals with normal metabolic function?

-normal inflammation

-normal metabolic control

-normal vascular function

structure: normal

what are the conditions of inflammation, metabolic control and vascular function and structure of AT in obese individuals with mild metabolic dysfunction?

-high inflammation

-low metabolic control

-normal vascular function

structure: normal but a bit bigger

what are the conditions of inflammation, metabolic control and vascular function and structure of AT in obese individuals with metabolic dysfunction?

-very high inflammation

-very low metabolic control

-low vascular function

structure: crown-like

once the cell gets bigger, what happens?

-they have a memory for getting big

what are the 2 types of anti-inflammatory adipokines?

1. adiponectin

2. SFRP5

what are the 11 types of pro-inflammatory adipokines?

1. leptin

2. resistin

3. RBP4

4. lipocalin-2

5. ANGPTL2

6. TNF

7. IL-6

8. IL-18

9. CCL2

10. CXCL5

11. NAMPT

leptin

-is a major player in appetite

-is an obese protein

-made by WAT

-influences appetite, satiety (feeling full), and food-motivated behaviours

-acts on the hypothalamus to regulate hunger and energy balance to help maintain weight

hypothalamus

-homeostatic center of the brain

what does high levels of leptin indicate?

-means energy reserves are high

-more body fat = more WAT = more leptin

what do low levels of leptin indicate?

-energy reserves are low

-less body fat = less WAT = less leptin

what is the process of high levels of leptin acting on the body?

• when leptin is detected in the brain by pro-opiomelanocortin (POMC) neurons, the hypothalamus releases melanocortins to suppress appetite

• (+) leptin → POMC/melanocortins → decrease food intake

what is the process of low levels of leptin acting on the body?

• when leptin levels are low (following a fast), agouti-related peptide (AgRP) neurons in the hypothalamus inhibit POMC cells and release neuropeptide Y, which stimulates hunger

• (-) leptin → AgRP/neuropeptide Y → increase food intake

what are POMC neurons also activated by…leading to…?

-they are activated by activated cannabinoid receptors… leading to the munchies

POMC neurons

-pro-opiomelanocortin neurons

-detect leptin hormone in the brain

-located in the hypothalamus

-inhibits AgRP

-stimulates suppression of appetite

-regulates energy balance, appetite, and metabolism by releasing signaling molecules

melanocortins

-released by the hypothalamus to suppress appetite

-a peptide hormone

-derived from POMC

-inhibits NPY

AgRP neurons

-agouti-related peptide neurons

-hunger-promoting neurons located in the hypothalamus that release AgRP and NPY

-stimulate appetite, decrease metabolism, and drive feeding behaviour

-inhibits POMC

neuropeptide Y (NPY)

-released by the hypothalamus to stimulate hunger

-a neurohormone

-inhibits melanocortins

leptin resistance

-occurs in obesity, causing an inability to detect satiety despite high levels and high energy reserves (makes people gain weight)

leptin overstimulation

-desensitizes brain receptors

-causes overeating in the presence of enough fat stores

what happens if leptin levels are too high?

-perceived lack of leptin causes the body to utilize fewer calories (lowers basal metabolic rate) and increases energy storage (brain thinks its starving)

-causes overeating in the presence of enough fat stores and desensitizes brain receptors (leptin overstimulation)

hyperphagia

-insatiable hunger

-leptin-deficient and leptin-resistant mice has this (as well as decreased energy expenditure)

what happens if you are leptin-deficient?

-the body thinks it has no body fat (no leptin), which causes voracious appetite, leading to class III obesity in children and delayed puberty

congential leptin deficiency

-as known as hypoleptinemia

-is a rare autosomal recessive condition that prevents adipose tissue from making leptin

what is the treatment for hypoleptinemia?

-treatment involves the drug metreleptin, a recombinant/synthetic form of human leptin that reverses the symptoms

metreleptin

-a recombinant/synthetic form of human leptin that reverses the symptoms of hypoleptinemia

what are the 9 factors affecting obesity?

1. environmental factors

2. social factors

3. psycological factors

4. biological factors

5. lifestyle

6. socio-economic factors

7. individual behavioural factors

8. health factors

9. sociodemographic factors

what are some of the consequences of obesity?

• cancer

• liver disease

• gallbladder problems

• type 2 diabetes

• weakened muscles and bones

• joint pain

• infertility

• kidney failure

• skin fold rashes

• gastroesophageal reflux disease

• sleep apnea

• high depression

• high risk of stroke

• high risk of heart attack

hypertension

-obesity leads to this

-heart works hard to pump blood, and blood forcefully pushes against the artery walls

what is our blood pressure measured in?

-it is measured in millimetres of mercury (mmHg)

systolic blood pressure

-pressure on artery walls when heart contracts (top)

diastolic blood pressure

-pressure between beats when heart relaxes (bottom)

systolic number

-is when the heart contracts

diastolic number

-is when the heart rests

what are the 2 types of blood pressures?

1. systolic BP

2. diastolic BP

atherosclerosis

-is the gradual buildup of plaque in the walls of arteries

-it affects different areas of the body such as heart, digestive system, legs and feet, kidneys and brain

-caused by high levels of triglycerides and low-density lipoprotein (LDL) cholesterol

triglycerides

-a lipid found in fat cells that stores unused calories

low-density lipoprotein cholesterol

-aka LDL cholesterol

-bad cholesterol

-transports cholesterol throughout bloodstream

which lipoprotein is the good cholesterol?

-HDL (high-density lipoprotein cholesterol)

what promotes insulin resistance?

-excess body fat, which increases the risk of Type 2 diabetes

insulin resistance

-cells don’t recognize what is happening

insulin

-hormone produced by the pancreas that triggers sugar uptake by cells to be used for fuel or storage

hyperglycemia

-high blood sugar

-can damage the eyes, kidneys, nerves, and heart

type 2 diabetes

-sugar (glucose) in the blood is having difficulty entering the cell

-no glucose is being uptaken (aka hyperglycemia occurs)

metabolic syndrome

-a group of clustered metabolic conditions that increase your risk of cardiovascular disease, Type 2 diabetes, and stroke