Lipid Metabolism II

Location of Adipose Tissue

Subcutaneous
Visceral

Brown Fat

There is evidence of active brown adipose tissue in adults.

Can be a target for treating obesity.

Fatty Acid Mobilization

TAG Diacylglycerol Monoacylglycerol Glycerol

First step regulated by Hormone-sensitive lipase (HSL)
Regulated by diet and hormones, phosphorylation and
dephosphorylation of HSL and Perilipin.
Glycerol transported to liver for gluconeogenesis.
Low insulin stimulates the rate of mobilization.

Regulation of Lipolysis in Adipose

Perilipin A binds and protect lipid droplets from lipases during

well-fed state.
Insulin stimulates dephosphorylation of Plin A and HSL
inactivated.
During fasting, PKA phosphorylates Perilipin and HSL causing
Perilipin A to bind HSL and activate lipolysis.
Catecholamines also stimulate lipolysis via PKA.
In obesity/metabolic Syndrome, there is a decrease in
adipose insulin receptors which leads to increased fat
mobilization and free fatty acid in the blood and fatty liver. Cause
non-alchoholic steatophpatitis (NAFLD/NASH)
FABP4 is a target of VEGF for endothelial cell growth.

Adipokines and Atherosclerosis

Lean adipose cells release anti-inflammatory adipokines such as

adiponectin.
Obese adipose cells release pro-inflammatory adipokines that
cause atherosclerosis.
Osteopontin is an activator of adipose macrophages and act as
an inflammatory cytokine.

Fatty Acid Flux in Adipocytes

FFA are released from lipoproteins by LPL

CD36 (FAT) is a cell surface protein that binds and imports long
chain FFA into the cytoplasm.

Lipodystrophies Disorder of adipose tissue biology that cause

abnormal adipose formation.
SIRT3 mediate metabolic responses to nutrient availability.
Fatty Acid Oxidation

Fatty acids taken up by cells and attached to CoA.

Fatty acyl group transported into the mitochondrial matrix by
Carnitine acyltransferase (CPT I/II)
Carnitine is recycled to the cytosol via translocase.
Short chain fatty acids can diffuse through the inner membrane.
Malonyl CoA inhibits CPT I during fatty acid synthesis.

Carnitine Synthesis

Made from lysine.

Vitamin C is required cofactor.

Beta Oxidation

Occur in matrix of mitochondria.

Oxygen in Keto groups come from H2O.
Palmitoyl CoA +7CoA +7FAD + 7NAD + 7H2O 8 Acetyl CoA +7
FADH2 + 7 NADH
FADH2 go to CoQ
NADH go to Complex I
Ketone bodies go to Krebs.
Catalyzed by Mitochondrial Trifuctional Protein (MTP)

Beta-Oxidation in Peroxisomes

Does not use NAD or FAD.

Oxidase Use O2 and generate H2O2.
Catalase hydrolyze H2O2 to H2O and O2.

Energy Calculations

Fat 9kcal/g (no water)

CHO 3.5kcal/g (water) 1kcal/g

Ketone Body Synthesis

Made in liver.
Acetyl-CoA is used to make Acetoacetate and betahydroxybutyrate.
HMG-CoA is an intermediate and also an intermediate for
cholesterol synthesis in the cytoplasm.
Ketone bodies are transported to other tissues to make ATP.
Prevent protein degradation in muscles.
Excess can lead to ketoacidosis, occurs in untreated diabetes,
starvation.
Excreted as conjugate bases in the kidneys, proton left behind.