Significant reductions in elevated heart rate

and systolic blood pressure without altering food intake.

A

significant decrease in food intake without any change in blood pressure.

A

transient increase in systemic vascular resistance and mean arterial pressure.

Enteroendocrine

L-cells

Hepatic

stellate cells

Kupffer

cells

Ballooned

hepatocytes

Intestinal

integrity is maintained entirely by Proteobacteria, with SCFAs having no

structural influence.

SCFAs

are toxic to the intestinal epithelium, and their reduction is protective

against systemic inflammation.

SCFAs

increase gut mucosal permeability, allowing dietary fats to enter systemic

circulation directly.

A

decrease in SCFAs impairs gut mucosal integrity, leading to a "leaky

gut" that permits translocation of lipopolysaccharide (LPS) into portal

circulation, activating resident hepatic Kupffer cells.

Reduced

mitochondrial number, defragmentation of mitochondria, and increased production

of reactive oxygen species (ROS).

Hypertrophy

of the outer mitochondrial membrane with a compensatory increase in fatty acid

oxidation.

Complete

degradation of all skeletal muscle mitochondria, shifting muscle metabolism

entirely to anaerobic glycolysis.

It

directly inhibits insulin receptor substrate 1 (IRS1) to reduce glucose

transport in states of obesity.

It

is an anti-inflammatory cytokine secreted exclusively by M1 macrophages to downregulate

skeletal muscle GLUT4.

It

binds to AdipoR, recruiting AMPK, promoting GLUT4 translocation and stimulating

beta-oxidation via ACC phosphorylation/inhibition.

It

binds to TNF receptors, activating JNK and suppressing downstream PI3K/AKT

signalling to prevent lipid accumulation.

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.

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.

Insulin

binds receptor →

activation of IRS1 →

activation of phosphoinositide 3-kinase (PI3K) → activation of Protein Kinase B (AKT) → translocation of GLUT4 vesicle channels to the

plasma membrane.

Insulin

binds receptor →

APPL1 recruitment →

ACC activation →

passive diffusion of glucose.

Insulin

binds receptor →

direct passive entry of glucose through lipid bilayers.

It

primarily synthesises insulin, regulates core body temperature, and directly

metabolises systemic glycogen.

It

is composed of exactly 50 species of bacteria that weigh approximately 10 kg in

a healthy adult.

It

has no role in digestion but is solely responsible for secreting systemic

inflammatory cytokines.

NAFLD

is the most common cause of liver disease, affecting 1/3 of the adult

population and approximately 12% of children worldwide.

NAFLD

is rare, affecting only 1% of adults and 0.5% of children worldwide.

NAFLD

is highly prevalent in developing countries but affects less than 5% of

populations in Western countries.

NAFLD

affects 90% of the adult population and 50% of children globally.