Liver And Adipose Tissue Flashcards
Functions of adipose tissue
Mechanical cushioning
Thermal insulation
Energy store
EndocrIne organ
2 types of adipose tissue
Brown
White
Brown adipose tissue
Mitochondria
Fat droplets
Develops from muscle cell progenitors
Metabolism generates heat so is important in children because of their high surface area to body mass ratio
No significant levels in adults
White adipose tissue
Fewer mitochondria
One single fat droplet
Controlled storage and release of fat
Where are fatty acids stored
In all cells
Primarily adipocytes
Stored for future use of triacylglycerols
Triacylglycerols
Molecules of glycerol and 3 fatty acids
Esterified
Predominantly saturated
Development of fat cell
Fibroblast like precursor cells receive hormone signals that trigger differentiation into sdipocytes
Cells alter gene expression pattern and accumulate lipid droplets
As lipids accumulate they. Edge to form mature fat cell (triglyceride droplet and nucleus)
Mature fat cells can’t divide but early stages are reversible
Thrifty genes
Permit more efficient food utilisation and fat deposition in times of abundance
Resulting in better survival in times of subsequent famine
Adipocytes in obesity
White adipose tissue as an organ
Metabolic integration
EndocrIne activity
What does white adipose tissue produce
Production of
Steroid hormones: oestrogen from androgens and cortisol from cortisone
Proteins of energy metabolism blood clotting And complement pathway
Cytokines for signalling
Peptide hormones including leptin
Leptin
Mutation in ob/ob mice was identified in gene producing protein called leptin
Produced primarily in adipose tissue in proportion of adipose mass
Leptin treatment reduces food intake and increases energy expenditure and reverses obesity in ob/ob mice
Why isn’t leptin an anti obesity drug
Leptin administration only effective in individuals who are obese due to leptin deficiency
Most obese people have high leptin concentration but fail to respond normally so have leptin resistance
Hormones secreted by adipocytes
Adiponectin
Resistin
TNF
IL6
fatty acids
Leptin function
Metabolic rate
Reproduction
Adiponectin function
Liver glucose production
Muscle glucose oxidation
Resistin function
Promotes insulin resistance
TNF function
Impairs insulin signalling
Il 6 function
Increases lipolysis
Glucose uptake
Fatty acids function
Impairs insulin production in pancreas
Sensitivity
Role of the CNS in weight regulation
2 regions
Lateral hypothalamus.
Ventromedial hypothalamus
Lateral hypothalamus
Hunger centre
Animals with lesions in this area become anorectic and lose weight
Ventromedial hypothalamus
Satiety centre
Animals with lesions in this area overeat and become obese
Appetite signals
Hormones involved in appetite
NPY
AgRP
POMC
Hormones involved in appetite
NPY
AgRP
POMC
NPY function
Neuropeptide Y – Neurotransmitter (Brain and ANS); INCREASE Food intake (orexigenesis), DECREASE physical activity.
AgRP function
Agouti-related peptide – Neuropeptide (Brain); INCREASE Appetite, DECREASE metabolism.
POMC function
Pro-opiomelanocortin – Hormone precursor (Pituitary); Regulates MSH (melanocyte stimulating hormone) which then regulates appetite and sexual behaviour!!
Where do hormones regulating appetite act
act at the hypothalamus
•leptin and insulin decrease appetite by inhibitory actions on NPY/AgRP neurons. They signal the well-fed state
•ghrelin, from the empty stomach, activates NPY/AgRP neurons.
Fat fat cells
Promote insulin resistance
Trigger low grade chronic inflammation
Leads to type 2 diabetes
High blood pressure
Cardiovascular disease
Increased cancer risk
Thin fat cells
More benignly regulate metabolic interplay between tissues
Release Adiponectin promotes glucose uptake into tissues
Major metabolic pathways in the adipocytes
Carbohydrate metabolism
Carbohydrate metabolism in the adipocyte in the fed state
Increased glucose transport — Elevated insulin levels in fed state leads to influx of glucose through insulin- sensitive transporter.
(2)Increased glycolysis — Increased intracellular glucose results in enhanced glycolysis. Glycolysis supplies glycerol phosphate for triglyceride synthesis.
(3)Increased hexose monophosphate pathway (HMP)— Metabolism of glucose through this pathway produces NADPH, which is essential for fat synthesis.
Fat metabolism in the fed state in adipocytes
Increased fatty acid synthesis — De novo synthesis from acetyl CoA is a major source of fatty acids in human adipose tissue only when re-feeding after a fast.
(6) Decreased triglyceride hydrolysis — Elevated insulin levels favors the dephosphorylated (inactive) state of hormone-sensitive lipase, preventing TG degradation and promoting storage.
Carbohydrate metabolism in adipocytes in fasting state
Glucose transport and metabolism are depressed due to low insulin levels. This leads to a decrease in fatty acid and triglyceride synthesis
Fat metabolism in fasting state of adipocyte
Increased triglyceride hydrolysis — The activation of hormone-sensitive lipase via phosphorylation leads to hydrolysis of stored TG. This activation is enhanced by noradrenaline released from sympathetic nerve endings in adipose tissue.
(2)Increased fatty acid release — Fatty acids liberated by TG hydrolysis are released into the circulation and transported to other tissues for use as fuel. The glycerol released by TG hydrolysis is used by liver for gluconeogenesis.
Where may fat be stored
Visceral
Subcutaneous
Visceral fat
Around abdominal organs
Particularly problematic
Signals sent to liver
Subcutaneous fat
Under skin
Metabolically less active
Less signalling molecules
Android
Upper body density
More common in men and post menopausal women
Risk for diabetes and hypertension
Larger fat cells
More easily mobilised fat stores
Ovoid
Overall obesity
Most common in people with genetic predisposition to obesity
Gynoid
Lower body density
More common in pre menopausal women
Fat stores not easily mobilised
Harder to lose weight
Relatively benign health wise except arthritis and varicose veins
Long term body weight regulation
Integration of hormonal metabolic and neural signals
BMI calculation
Weight in kg/ height in m2
<18.5 underweight
18.4-24.9 normal
25-29.9 overweight
>30 obese
