Summary Lecture Notes Lipids in Health and Disease | KU Leuven | 2025/26

CONTENT

Biochemistry of lipids.............................................................................................................1
General principles of mass-spectrometry..............................................................................5
Lipids and cancer....................................................................................................................9
Cardiovascular disease: mechanistic aspects.......................................................................13
Lipids in neurodegeneration: the Charcot-Marie-Tooth Case.............................................17
Increased cardiovascular risk in patients with chronic kidney disease................................20
Fatty acids and brain disease................................................................................................23
Applications: lipid-based nano- & micromaterials...............................................................26
Key questions..................................................................................................................30



SUMMARY LIPIDS IN HEALTH AND DISEASE

Biochemistry of lipids
Lipids = organic molecules that are scarcely soluble in water (= hydrophobic) but it can also
have hydrophilic parts (= amphiphilic)

 Function: compound of cell membranes, source of energy & signalling

Groups of lipids

, 1. Simple

= formed of fatty acids (FA) and alcohol without any additional group

 Fatty acids

= chain of carbon atoms with methyl group (CH3) & hydrophilic carboxylic acid head (COO-)

Kinds: saturated (no double bond), monounsaturated (1 double bond) or polyunsaturated
(+1 double bond)

Nomenclature:

- Delta(Δ)/omega(w) nomenclature = #carbons: # of double bonds Δx or w-x (x =
placement double bond starting from COO- (Δ) or CH3 (w))
- Common name
- Cis/trans notation = C #carbons: # of double bonds (x Z or E) -> x = placement double
bond, E = trans, Z = cis (position H-atoms one same side)
- Length = short (C2-6)/medium (C7-12) /long (C13-21) /very long (C22-...) -chain FA



How do we get fatty acids?

- Food
- Fatty acid synthesis: starting from acetyl-CoA (2C), each cycle in the cytosol adds 2C
until 16C (breakdown in mitocondria –2C each cycle). Our body further differentiates
the FA with elongases and desaturases. But the human body doesn’t have all the
enzymes to make all the fatty acids (plants do have them so we need to get those FA
from our food = essential fatty acids)

Function

- Membranes: the more unsaturated the more flexible/fluid/fragile the membrane will
be, because the FA will not have a linear structure when they have double bonds (<-
> saturated = more rigid = more cell contact)
- Activating receptors (e.g. PPARs) or are involved in posttranslational modifications
(e.g. palmitoylation)
- Short FA have a protecting effect on the body



 Triglycerides (TG)

= represent the major form of storage and transport of fatty acids within cells & plasma.
Glycerol backbone is esterified with 3 fatty acids. 2 or 1 => di- or monoglycerides (DG/MG)

, Sn = Stereospecific Numbering

Name = TG (Sn1 + Sn2 + Sn3 : # of double bonds) -> e.g. TG(46:1)

Where do they come from?

- Dietary TG are processed in the cell and form chylomicrons
- Break: Adipose TG Lipase -> Hormone Sensitive Lipase -> MonoacylGlycerol Lipase
- Synthesis: DG or MG acyltransferase (DGAT/MGAT: transfers FA towards molecule)




2. Compound

= contain groups in addition to FA and alcohol

 Phospholipids (PL)

= key components all cell membranes, can form lipid bilayers -> amphiphilic characteristic.




They consist of 2 fatty acids (= hydrophobic tail), a glycerol unit and a phosphate group
which is esterified to an organic molecule (head group = hydrophilic + variations).

- Phosphatidylcholine (PC) -> membrane enclosed vesicles (communication)
- Phosphatidylethanolamine (PE) -> membrane enclosed vesicles (communication)
- Phosphatidylglycerol (PG)
- Phosphatidylinositol (PI) -> phosphate can be added -> signaling, regulation, ... (PIP)
- Phosphatidylserine (PS) -> signaling immune cells when in outer leavlet (apoptotic)

Kennedy pathway = a complex pathway that leads to the formation of PC and PE. These can
be transformed into many other phospholipids.

Lands’ cycle = constantly remodeling of phospholipids in the cell membrane. FA are cleaved
of by phospholipase A2 -> lysophosphlipids (= phospholipid –1 FA) -> new FA (Acyl-CoA) is
attached by the enzyme lysophospholipid acyltransferase. Happens constantly.