Ependymal cells

Schwann cells

Oligodendrocytes

Astrocytes

Thalamus

Hippocampus

Subventricular zone

Striatum

The beneficial effects of exercise to improve insulin sensitivity and glucose metabolism are dependent on weight loss

Increased

energy expenditure in response to exercise primarily occurs in major organs

such as the brain, kidneys and gut

120 min of low intensity exercise per week is sufficient in causing clinically significant weight loss

Weight loss causes a long-term decrease in

leptin, this coincides with increased ghrelin leading to activation of the

NPY/AGRP neurons and inhibition of POMC neurons

Weight

loss causes a long-term decrease in leptin, this coincides with increased

ghrelin leading to elevated food intake but no direct change in energy

expenditure

Weight

loss causes a sustained increase in ghrelin secretion this causes long-term

activation in the NPY/AGRP neurons without any change in POMC activity

After

a meal, the rise in the gut satiety peptides GLP-1, PYY and CCK is attenuated,

this leads to increased hunger that is relayed only via the vagal afferents

from the stomach to the brainstem

GWAS

are important in identifying monogenetic mutations that can lead to obesity and

aberrant metabolic function

FTO

over-expression in mice increases intake of highly caloric foods without an

associated change in energy expenditure, leading to increased fat mass

Increased

food intake without any observable changes in food preference, which leads to

weight gain

FTO over-expression in mice increases intake of

highly caloric foods and reduces energy expenditure via both physical activity

and ‘browning’ of white adipose tissue

Show no plasticity and once

recruited in white adipose tissue depot remain as beige adipocytes

Are produced de novo within white adipose tissue

depots in response to activation of the sympathetic nervous system and cold

exposure

Are specific to rodents and

are NOT found in thermogenic tissue regions such as the supraclavicular or neck

areas in humans

Are derived from Myf5+ve

brown adipocyte precursor cells and are recruited in response to cold exposure

In humans, brown adipose tissue levels decline during early life as muscle develops the ability to shiver, however BAT is reinstated across puberty

In brown adipose tissue, adaptive thermogenesis is enhanced in the β-less mice that lack all three β-adrenergic receptors

In brown adipose tissue, activation of the SNS causes lipolysis and the mobilisation of triglycerides, which can activate UCP1 and cause thermogenesis

In skeletal muscle, adaptive thermogenesis occurs via futile calcium cycling and NOT mitochondrial uncoupling pathways

Adjustable

gastric band surgery increases the secretion of GLP1, which improves glycaemic

control

Sleeve

gastrectomy surgery reduces circulating levels of ghrelin, which is thought to

be a key determinant of improved glucose tolerance

Adjustable

gastric band surgery acutely improves glucose tolerance and insulin sensitivity

without associated weight loss

Sleeve gastrectomy surgery increases the

secretion of GLP1, which increases glucose-stimulate insulin secretion

Lipotoxicity

increases the concentration of ceramides in myocytes, ceramides inhibit insulin

signalling by directly blocking the phosphorylation of IRS-1

Lipotoxicity leads to increased levels of

long-chain fatty acids, the ceramides and diacylglycerols (DAGs) because of

partial oxidation of fatty acids, which in turn interfere with insulin

signalling

Lipotoxicity

leads to increased production of short-chain fatty acids, the ceramides and

diacylglycerols (DAGs) because of complete oxidation of fatty acids, which in

turn interfere with insulin signalling

Lipotoxicity

increases the concentration of diacylglycerides (DAGs) in myocytes, DAGs

inhibit insulin signalling by directly blocking the phosphorylation of Akt

Mutations in the leptin receptor are associated with elevated circulating levels of leptin and late onset obesity

Mutations in the leptin gene lead to elevated levels of circulating leptin, resulting in the development of leptin resistance

Mutations in the leptin receptor are associated with elevated circulating levels of leptin and early-onset of obesity