Unit II week 2 Flashcards
Rank in order from most polar to nonpolar:
free fatty acids cholesterol cholesterol esters triglycerides phospholipids
Most polar: fatty acid
- -> phospholipids
- -> cholesterol
- -> triglyceride
- -> cholesterol ester (most nonpolar)
Types of specialized lipids: (4)
1) Phospholipids
2) Sphingolipids
3) Glycosphingolipid
4) Molecules made from arachidonic acid
Glycerophospholipids
structure
glycerol backbone + PO4 group attached
located at interface of lipid and aqueous in membranes or at the surface of lipoproteins
amphipathic molecule
Glycosphingolipid
structure
ceramide backbone + sugar residue on head group
De Novo Lipogenesis occurs when _______ is present in ______ or _______ tissues in excess
glucose
liver, adipose
De Novo Lipogenesis
1) Acetyl CoA + ________–> ______ (leave ______ and enter ______)
2) Citrate –> _______ in the ________
3) Acetyl CoA –> ________ via _______ enzyme
4) ______ CoA units are put together 2 carbons at a time by _________ (enzyme) to form growing fatty acid chain (first 2 carbons from ______ CoA)
1) Acetyl CoA + OAA→ citrate (leave mitochondria, enter cytosol)
2) citrate –> aceyl CoA (cytosol)
3) Acetyl CoA → Malonyl CoA by acetyl-CoA carboxylase
4) Malonyl CoA units are put together 2 carbons at a time by fatty acid synthase to form growing fatty acid chain (first 2 carbons from acetyl CoA)
Malonyl CoA
inhibits _________
important intermediate of fatty acid synthesis
Inhibits Carnitine Palmitoyl Transferase 1 (CPT-1)
–> Inhibits Beta-oxidation of fatty acids (pathway going in opposite direction)
Fatty acid synthase
Uses NADPH (hexose monophosphate pathway) for energy
Converte malonyl CoA —> fatty acids (palmitate) via addition of carbons 2 at a time
first 2 carbons come from acetyl CoA
Acetyl-CoA carboxylase
why is it important? what reaction does it catalyze?
Activated by _______
Inhibited by ____________
Converts Acetyl CoA → Malonyl CoA
Rate limiting step in fatty acid synthesis
Activated by citrate
Inhibited by long chain fatty acyl CoA
Fatty acids are packaged with ______ –> ________ –> circulate in blood as ________
Then taken up by adipose tissue through _________ –> stored and used when body is in negative energy balance
glycerol –> triglyceride
VLDL
Lipoprotein lipase
Hormone sensitive lipase
insulin low, counterregulatory hormones high → breaks down triglyceride in adipose tissue
Releases fatty acids and glycerol → enter circulation, taken up by liver
Beta oxidation
occurs when body in negative energy balance (exercise, short-term fasting)
Provides source of energy to preserve glucose for the brain and provides energy (ATP) needed for gluconeogenesis in liver
Steps of Beta oxidation
1) __________ breaks down ________ releasing fatty acids and glycerol into circulation –> taken up by ________
2) Once there…
Glycerol –> substrate for ________
Fatty acid –> __________
3) Fatty acid in _______ of hepatocyte –> converted to __________ –> enters _______ via ______________
4) 2 carbons at a time removed from _________ as ________ –> can enter __________ pathway
1) Hormone sensitive lipase, triglycerides, liver
2) glycerol = substrate for gluconeogenesis
Fatty acids = energy source for gluconeogenesis
3) cytosol, converted to acyl-carnitine
enters mitochondria via carnitine palmitoyl transferase 1 (CPT1)
4) 2C removed at a time from fatty acyl CoA as acetyl CoA –> can enter TCA cycle
Ketogenesis
insulin very low/absent, counterregulatory hormones high (long-term fasting, ketogenic diet, DKA)
Acetyl CoA produced by B-oxidation in liver can become a ketone body
Ketones = alternate fuel for brain and other tissues in states of prolonged dietary glucose insufficiency
Ketone bodies formed during: ________, _________, and _______
because of what 3 conditions?
starvation, DKA, alcoholic ketoacidosis
1) Very low insulin levels
2) High counterregulatory hormones
3) Abundant source of substrate (fatty acids, ethanol)
**Ketones only formed when acetyl CoA produced by fatty acid metabolism (or ethanol metabolism) exceeds capacity of TCA cycle to metabolize it (ATP/ADP is high)
HMG CoA synthase
rate limiting step in ketogenesis (synthesizes hydroxyl methylglutaryl CoA)
Occurs in mitochondria
Cholesterol synthesis
Cholesterol synthesis from _______ through formation of ________
rate limiting step?
location in cell?
does it require energy?
Cholesterol synthesis from acetyl CoA through formation of hydroxymethyl glutaryl CoA
- *HMG CoA Reductase: rate limiting step in cholesterol synthesis
- Occurs in cytosol
- Uses NADPH for energy
Lipoprotein pathways: 3 pathways
1) Dietary fat pathway (Chylomicron pathway)
2) VLDL pathway
3) HDL pathway
Fatty Acids
hydrophobic hydrocarbon chain + terminal carboxyl group (- charge in body)
Amphipathic nature
Long chain fatty acids
hydrophobic portion predominates, water insoluble, transported in circulation with proteins
Typically components of cell membranes
Saturated vs. unsaturated fatty acids
Saturated fatty acids: contain no double bond
Unsaturated fatty acids: contain one or more double bonds (cis) → bending, decreases melting temperature (liquid at room temperature, increased fluidity)
Naming fatty acids:
Length of carbon chain (beginning with carboxyl carbon as 1), and number of double bonds (+ position of double bonds)
Omega = end closest to methyl group
________ and _________ are dietary essential fatty acids because human cells do not have enzyme to introduce double bonds between carbon _____ and _______ end of fatty acids
Linoleic acid (omega 6) and Linolenic acid (omega 3)
carbon 9 and omega end
Linoleic acid → ?
Linolenic acid → ?
Linoleic acid → precursor for arachidonic acid (PG synthesis)
Linolenic acid → important for growth and development
Palmitate
16 chain carbon chain synthesized from Malonyl CoA by Fatty Acid Synthase
Fatty acids synthesized 2 carbons at a time
First two carbons taken from acetyl CoA (not malonyl CoA) and the rest are from malonyl CoA
Elongation and desaturation of fatty acids occurs where and how?
Elongation → in mitochondria and ER by Fatty Acid Elongase
Desaturation (introduction of cis double bonds) → in ER by mixed function oxidase
Mitochondrial acetyl CoA produced from oxidation of _________ and catabolism of _________, _________ and __________
oxidation of pyruvate and catabolism of fatty acids, ketone bodies, and some AAs
High levels of ________ inhibit _________ allowing _______ to build up in the cytosol of ________ or _______ cell, promoting lipogenesis
ATP inhibits TCA cycle
build up of citrate in cytosol of hepatocyte or muscle
Regulation of Acetyl CoA Carboxylase (ACC)
4 main regulators
1) Citrate (cytosol) → activate ACC by polymerizing the enzyme and increasing Vmax
2) Fatty acid CoA (Palimitoyl CoA, long chain fatty acid) –> depolymerize ACC → inhibition of ACC (starvation or high fat diet)
3) Insulin → fatty acid synthesis by activating protein phosphatase → dephosphorylates ACC (ACTIVATES enzyme)
4) Glucagon → increase cAMP → activate protein kinase → phosphorylate ACC (INACTIVATE enzyme)
Metabolic regulation of fatty acid synthesis:
High carb –> ?
High fat, low carb –> ?
High insulin –>
High glucagon –> ?
1) High carb → HIGH PYRUVATE and ACETYL COA levels in mitochondria → translocation of CITRATE from mitochondria → cytosol → stimulate fatty acid synthesis
2) High fat, low carb → LOW PYRUVATE flux into mitochondria, ELEVATED ACYL COA from fat metabolism in cytoplasm → reduced fatty acid biosynthesis
3) High insulin → fatty acid biosynthesis
4) High glucagon → lipolysis (B-oxidation)
Long-term regulation of fatty acid synthesis
prolonged consumption of excess calories → increase transcriptional expression of acetyl CoA carboxylase and fatty acid synthase
Fasting → reduced expression of acetyl CoA carboxylase and fatty acid synthase
Fatty acids are stored as _________
Triacylglycerols (TAGs)
Synthesis of TAGs:
In liver vs. in other tissues
In liver and adipose tissues: glycerol-3-phosphate made from glucose via glycolysis
In liver only: glycerol kinase directly phosphorylates glycerol to produce glycerol-3-phosphate
Activated fatty acids added to glycerol-3-phosphate
Storage of TAGs
TAGs made in liver → packaged with cholesterol, phospholipids, and apoB-100 → VLDL particles secreted into blood → coalesce with adipocytes
Fatty liver disease
results from chronic alcoholism typically
Occurs when anabolic and uptake pathways for triacylglycerol in liver increase and/or catabolic or secretion pathways decrease
How ethanol causes hyperlipidemia:
Ethanol → acetyl CoA (in liver) → Fatty acids + NADPH
High NADH concentration → DHAP → Glycerol-3-P
Glycerol-3-P + fatty acids → triglyceride
Liver secretes abnormally high levels of VLDLs and eventually chronic liver dysfunction impairs protein synthesis (can’t make ApoB-100)
→ Liver unable to produce VLDL → hepatic fat build up
Fatty acid oxidation:
under ________ conditions, fatty acids are released from _________ by ___________ –> fatty acids brought to ______ or ______
–> degraded by B-oxidation –> ________, ________ and __________
Under starvation conditions:
fatty acids released from triacylglycerols (TAGs) by hormone sensitive lipases → fatty acids brought to liver/muscle → degraded by B-oxidation → FADH2, NADH, and acetyl CoA (can generate 12 ATP via TCA cycle)
Main steps of fatty acid oxidation (3)
1) Release of fatty acid from triacylglycerols (TAGs)
2) Transport of fatty acids into mitochondrial matrix
3) Repeated cycles of oxidation: Beta-Oxidation
Release of fatty acids from triacylglycerols (TAGs) by what and how?
Initiated by hormone sensitive lipase (HSL) → removes fatty acid from carbon 1 and/or 3 of TAG
→ release of FAs and glycerol
Transport of fatty acids into mitochondrial matrix:
1) Fatty acids –> ________ in _________
2) Fatty acid degradation then occurs in the _________ and in order to do this, ____________ must be transported by ______________.
____________ can diffuse into matrix without carnitine.
Fatty acids → Acyl CoA in cytosol
Fatty acid degradation occurs in MITOCHONDRIA, BUT LONG CHAIN ACYL CoA molecules
temporary transfer carnitine and transport via carnitine palmitoyl transferase I (CPT-I)
short/medium chain FAs
carnitine palmitoyl transferase I (CPT-I)
- Long chain acyl (fatty acid) group transferred temporarily to carnitine via carnitine palmitoyl transferase I (CPT-I) and transported into mitochondrial matrix
- RATE LIMITING STEP in B-oxidation
- Allosterically inhibited by malonyl CoA (high when fatty acid synthesis is active)
4 steps of Beta oxidation
1) _________ (enzyme) uses ______ to oxidize acyl CoAs to introduce a _____ double bond
2) _________ adds water across trans double bond
3) ___________ generates B-keto acyly-CoA and ________
4) ___________ releases acetyl CoA from fatty acid chain and prepares fatty acid chain for another roung od B-oxidation
1) Acyl CoA Dehydrogenase (4 forms depending on length of carbon chains in fatty acid), FAD, trans double bond
2) Enoyl CoA Hydratase
3) B-Hydroxy-CoA Dehydrogenase, NADH
4) Thiolase
Beta oxidation occurs in the __________ of cells
mitochondria
Oxidation of odd number chain fatty acids:
Last round of oxidation leaves a fatty acyl CoA with 3 carbons…
1) __________ adds a carboxyl group to the fatty acid → ______________
2) D methylmalonyl CoA → _____________ by ______________
3) L Methylmalonyl CoA → _________ by _____________ (requires ____ cofactor) → enters TCA cycle
1) Propionyl CoA carboxylase adds a carboxyl group to the fatty acid → D-methylmalonyl CoA
2) D methylmalonyl CoA → L methylmalonyl CoA by methylmalonyl CoA racemase
3) L Methylmalonyl CoA → succinyl CoA by methylmalonyl CoA mutase (requires B12 cofactor) → enters TCA cycle
Deficiency of methylmalonyl CoA mutase or B12
causes methylmalonic acidemia and aciduria because of propionate and methylmalonate accumulation in cells
mutase responsible for conversion of L Methylmalonyl CoA → succinyl CoA
Peroxisomal B-oxidation
Peroxisomes major site of B-oxidation
Very long chain/branched fatty acids are preferentially oxidized in peroxisomes
Medium chains fatty acids exported from peroxisomes → mitochondria for further oxidation
Zellweger syndrome
x linked adrenoleukodystrophy due to defects of peroxisomal B-oxidation
Regulation of Fatty Acid Oxidation: 2 main points of regulation
Hormone Sensitive Lipase (HSL)
Carnitine palmitoyltransferase I (CPT-I)
Hormone Sensitive Lipase (HSL)
regulation:
- active when…
- inactive when…
Responsible for release of fatty acids from TAGs
Active when phosphorylated by cAMP dependent protein kinase (binding of epinephrine → activate AC)
Inactive when dephosphorylated by high insulin/glucose
Carnitine deficiency
Carnitine needed for CPT-I transport of long chain acyl CoA into mitochondria for B-oxidation
genetic disorder that results in massive amounts of TAG deposits in liver
→ muscle cramping, hypoglycemia, weakness, death
Ketogenesis occurs in the ___________ of a cell
mitochondria
Key steps of ketogenesis (4)
1) Formation of acetoacetyl CoA
2) Mitochondrial HMG CoA synthase: acetyl CoA + acetoacetyl CoA → HMG CoA
3) HMG CoA → acetoacetate + acetyl CoA
4) Acetoacetate → 3-hydroxybutyrate + NAD or Acetoacetate → acetone
Ketogenesis:
Formation of acetoacetyl CoA
2 acetyl CoA → acetoacetyl CoA
Via reversal of thiolase reaction of fatty acid oxidation
Mitochondrial HMG CoA synthase
acetyl CoA + acetoacetyl CoA → HMG CoA
Rate limiting step in ketogenesis
Ketogenesis
HMG CoA –> _________ + _________ via _________
HMG CoA → acetoacetate + acetyl CoA
Via HMG CoA lyase
Acetoacetate can go down 2 different paths to generate a ketone body. What are they?
Acetoacetate → 3-hydroxybutyrate + NAD
-High levels of NADH during fatty acid oxidation promotes conversion of acetoacetate → 3-hydroxybutyrate
OR
Acetoacetate → acetone
_________ and _________ are ketone bodies
Acetone and 3-hydroxybutyrate = KETONE BODIES
Use of Ketone Bodies:
Ketone bodies are primarily produced in the _______, but in order to be used, they must…
LIVER
→ diffuse in blood to peripheral tissues and act as primary fuel source for muscle and brain (and other tissues if glucose is low)
Once ketone bodies are in the blood stream what happens to them?
**3-hydroxybutyrate converted to acetyl CoA
3-hydroxybutyrate → acetoacetate + NADH → Acetoacetyl CoA (addition of CoA from succinyl CoA) → 2 Acetyl CoA
→ enters TCA cycle for energy
**Acetone eliminated
-Acetone only produced in small amounts
Eliminated in urine or breath
NADH role in regulation of ketogenesis
elevated NADH during fatty acid oxidation → inhibit TCA cycle enzymes → accumulation of acetyl CoA → ketone body synthesis
NADH inhibits pyruvate dehydrogenase, activates pyruvate carboxylase
NADH favors formation of 3-hydroxybutyrate
Ketoacidosis
extremely high levels of ketone bodies released during periods of extreme metabolic stress
Rate of ketone body formation > rate of use → [ketone bodies] rises in blood and then urine
both ketones are acids, so cause acidosis when elevated in the blood
Type 1 diabetes and ketoacidosis
lack insulin → hormone sensitive lipase highly activated → release large quantities of fatty acids from adipose
→ Fatty acid oxidation (produces lots of NADH) → inhibit TCA cycle
→ Excess acetyl CoA generated from fatty acid oxidation → ketone body formation
Ketone bodies are moderately strong acids → lower blood pH → metabolic ketoacidosis
Acetone = highly volatile (“fruity odor”)
Sources of cholesterol in the liver (4)
1) Diet (only about 300-600 mg)
2) Enterohepatic circulation (bile acid recycling)
3) Synthesis (about 1g per day)
4) LDL and HDL cholesterol returned from circulation
Major ways HMG CoA Reductase is regulated (3)
1) Transcriptional regulation
- Sterol Regulatory Element Binding Protein (SREBP)
- Glucagon, insulin
2) Translational regulation
3) Degradation and phosphorlyation
When cholesterol is present in excess how is HMG CoA Reductase regulated via TRANSCRIPTIONAL changes
Cholesterol present in excess → DECREASE HMG CoA reductase gene transcription
SREBP binds SCAP and keeps SREBP in golgi –> SREBP does NOT stimulate HMG CoA reductase transcription in nucleus
Effect of glucagon and insulin on HMG CoA Reductase
Glucagon DECREASES expression of HMG CoA reductase gene
Insulin INCREASES expression of HMG CoA reductase gene (insulin high in fed state when NADPH high → excess acetyl CoA)
Sterol Regulatory Element Binding Protein (SREBP)
what it does when cholesterol is high vs. low
transcription factor that regulates HMG CoA Reductase transcription
Cholesterol low → SREBP released, moves to nucleus to stimulate transcription of HMG-CoA reductase
Cholesterol high –> bind SCAP protein in golgi and NOT stimulating HMG CoA reductase transcription in nucleus
Translational regulation of HMG CoA Reductase
Cholesterol in excess → reduce translation of mRNA encoding HMG CoA reductase and decreased mRNA half life
Degradation and Phosphorylation of HMG CoA Reductase
Cholesterol in excess → reduce half life of HMG CoA Reductase (11 → 2 hrs) and AMP kinase phosphorylates (inactivates) HMG CoA Reductase
Steps in de novo cholesterol synthesis
1) Acetyl CoA → HMG CoA
2) HMG CoA → Mevalonate
3) Mevalonate → Cholesterol
Energy requiring pathway (ATP x2 and NADPH x2) → occurs in fed state
Acetyl CoA –> HMG CoA
catalyzed by what enzymes and where?
Catalyzed by thiolase and HMG CoA Synthase
Liver → two isoforms
- Cytosol → cholesterol synthesis
- Mitochondria → ketone generation
HMG CoA Reductase
HMG CoA → Mevalonate
Key rate limiting step in cholesterol synthesis
Highly regulated
Occurs in CYTOSOL
Uses NADPH as reducing agent
geranyl pyrophosphate and farnesyl pyrophosphate
Key intermediates from the cholesterol synthesis pathway
Glycerophospholipids
structure
4 examples
make up the bulk of membrane lipids
Structure: [Glycerol] + fatty acid + fatty acid + PO4-alcohol
EX) Phosphatidylserine (PS), Phosphatidylinositol, Phosphatidylethanolamine (PE), Phosphatidylcholine (PC)
Phosphatidylserine (PS)
gylcerophospholipid
important for membrane synthesis
Synthesized by base exchange reaction
Phosphatidylinositol
gylcerophospholipid
Important in signal transduction
Reservoir for arachidonic acid (PG synthesis)
Important membrane protein anchoring
Phosphatidylethanolamine (PE)
gylcerophospholipid
one of most abundant phospholipids in the body
Phosphatidylcholine (PC)
gylcerophospholipid
one of most abundant phospholipids in the body
Main component of lung surfactant and in bile
Sphingomyelin
structure
where in the body is it located primarily?
sphingolipid
Structure: [sphingosine] (aka ceramide) + fatty acid + PO4-Choline
Major structural lipid in nerve tissue
Sphingosine
backbone component in sphingolipids and glycosphingolipids
built from serine (AA) +fatty acid (palmitate)
Glycosphingolipid
Structure: [sphingosine] + FA + mono/oligosaccharide (head group)
Lipids primarily in brain and peripheral nerves
EX) Cerebroside, globoside, ganglioside
Synthesis of Glycerophospholipids
how they acquire their headgroups
Backbone comes from phosphatidic acid (precursor to triglyceride biosynthesis) then polar head group is added
PC and PE head groups formed de novo or come from diet → activated by CPD then attached to backbone
“Base exchange” = head groups exchanged onto previously synthesized phospholipids
Synthesis of arachidonic acid and prostaglandins
Synthesized from dietary fat (linoleic acid) → converted to arachidonic acid → prostaglandin (COX enzyme) or leukotrienes (5-lipoxygenase enzyme)
Five classes of lipoproteins
1) Chylomicrons
2) VLDL
3) Remnant particles (IDL)
4) LDL
5) HDL
Chylomicrons
made by GI tract from dietary fat
10:1 triglyceride > cholesterol
Responsible for rise in triglyceride level after meals
Very Low Density Lipoproteins (VLDL)
5:1 triglyceride > cholesterol
Made by liver –> Deliver triglyceride to peripheral tissue between meals
Source of basal triglyceride production
Decreased production post-meal
Remnant particles and Intermediate Density Lipoproteins
Metabolic byproducts of metabolism of chylomicrons and VLDL
Relatively CHOLESTEROL ENRICHED after TG delivered to peripheral tissues (tri=cholesterol)
Taken up by liver via remnant receptor
Low Density Lipoproteins (LDL)
produced from metabolism of VLDL
Cholesterol > TG → very atherogenic (more dense, smaller, the more atherogenic)
Cleared from circulation by liver via uptake by LDL receptor
High Density Lipoproteins (HDL)
“Trash trucks” of lipid metabolism
Collect cholesterol form peripheral tissues and transport it back to liver
Reservoir of phospholipids for other lipoprotein particles
Can exchange triglyceride and apo-proteins with other particles in circulation
Anti-atherogenic
Chylomicron pathway
1) In the small intestine, triglycerides are broken down by _______ into ________ and __________
2) Lipids then diffuse/transported across intestinal wall
3) _______ are RE-synthesized and packaged into ________ with apo_______
1) Triglyceride → monoacylglycerol + free fatty acids
by LIPASE
2) Lipids diffuse/transported across intestinal wall
3) Triglycerides RE-synthesized and packaged into chylomicrons with apoprotein B48
Chylomicron pathway
4) Chylomicrons are secreted in ______ –> enter central circulation –> acquire apo_____ and _______ from _________
5) TG in chylomicron broken down by _________ at endothelial surface of ______ and _______ tissues
**this enzyme requires _______ as a cofactor!
6) Results in production of ___________ –> taken up by liver by _______ receptors
4) Chylomicrons secreted in LACTEALS (gut lymphatics) → enter central circulation → acquire apoproteins *C-2 and *E from *HDL
5) Triglyceride in chylomicron broken down by LIPOPROTEIN LIPASE (LPL) at endothelial surface of MUSCLE AND ADIPOSE
LPL requires apoprotein C-2** as cofactor
6) Results in production of chylomicron-remnant particles → taken up by liver by remnant receptors (remnant particles not present in fasting state)
Without apo-C-2 on chylomicrons what happens?
No C-2 → no triglyceride breakdown by LPL → hypertriglyceridemia
VLDL pathway
1) VLDL secreted from _______ with apo ______ attached
2) VLDL acquires apo ______ and apo ______ from ________ in peripheral circulation
3) VLDL metabolized by ______ → ________
4) ______ cleared from body by ________ via endocytosis into ___________
**apo ______ is a cofactor for the LDL receptor, so LDL particles must have apo ______ on them in order to be cleared
1) Secretion of VLDL from liver with apoB100
2) VLDL acquires apoprotein C-2* and apolipoprotein E* from HDL* in peripheral circulation
3) VLDL metabolized by LPL –> LDL
4) LDL cleared from body by LDL receptor via endocytosis into LIVER
**apo B100 is a cofactor for the LDL receptor, so LDL particles must have apo B100 on them in order to be cleared
HDL pathway
1) HDL contains apo ______ which allows HDL to circulate in plasma and pick up _________
2) HDL can pick up free cholesterol in tissues via ________ or ________ which requires help from __________
1) HDL contains apo A1 which allows HDL to circulate in plasma and pick up FREE CHOLESTEROL
2) HDL can pick up free cholesterol in tissues via DIFFUSION or FACILITATED TRANSPORT which requires help from ABC-A1 CASSETTE
HDL pathway
3) Free cholesterol on HDL is “trapped” in particle by conversion to _________ by ___________
4) _____________ allows maturing HDL particle to transfer cholesterol esters to VLDL in exchange for triglycerides
5) HDL also serves as reservoir for apo____ and _____ which it can donate to ______ and _______
3) Free cholesterol on HDL is “trapped” in particle by conversion to CHOLESTEROL ESTER (less polar) by lecithin cholesterol acyltransferase (LCAT)
4) Cholesterol ester transfer protein (CTEP) allows maturing HDL particle to transfer cholesterol esters to VLDL in exchange for triglycerides
5) HDL also serves as reservoir for apo C2 and E which it can donate to VLDL and Chylomicrons
Apolipoproteins act as…(3)
1) Structural scaffold backbone of lipoprotein particle
2) Enzymatic cofactors/regulators
3) Ligands for receptors
Apolipoproteins that act as structural scaffold backbone of lipoprotein particle
(3)
ApoB48 → chylomicrons
ApoB100 → VLDL and LDL
ApoA1 → HDL
Apolipoproteins that act as enzymatic cofactors/regulators
ApoC2 → cofactor for LPL
ApoC3 → inhibits LPL
Apolipoproteins that act as ligands for receptors
ApoB100 → ligand for LDL receptor
ApoE → ligand for remnant receptor
Cholesterol ester transfer protein (CETP)
Allows maturing HDL particle to transfer cholesterol esters to VLDL in exchange for triglycerides
Occurs when tg levels are high, provides alternate route of tg clearance
ABC-A1 cassette
ATP binding cassette (ABC) transporter
Important in transport of cholesterol from peripheral tissues to apo A-1 (core apoprotein of HDL)
Lecithin cholesterol acyltransferase (LCAT)
Lecithin cholesterol acyltransferase
Transfers fatty acid from phospholipid onto free cholesterol → esterified cholesterol, that is more nonpolar and more tightly bound to HDL
Tangiers disease
lack ABCa1 protein → unable to remove cholesterol from peripheral tissues → very low HDL levels, premature atherosclerosis (“orange tonsils” due to accumulation of cholesterol in lymphatics)
LCAT deficiency
low levels of HDL, corneal opacities, renal insufficiency, hemolytic anemia due to accumulation of unesterified cholesterol in tissues
Exercise and fat/carb usage by skeletal muscle as intensity increases
1) When exercise begins glucose is the primary fuel
2) Then with sustained low intensity exercise, fat oxidation predominates
3) As intensity increases glucose oxidation predominates
4) As intensity increases further, anaerobic metabolism predominates and lactate production increases
Fat oxidation vs. carbohydrate oxidation and exercise
At low exercise intensities, fat is preferred substrate (although always some glucose oxidation)
Oxidation of fat yields more ATP than CHO, but ATP synthesis from CHO is much faster
**The point at which you switch off fat oxidation and go to CHO increases the more trained you are
Once glycolysis is in action, lactate levels continue to rise until a certain point and you stop exercising
Epinephrine and exercise
released from adrenal medulla, release is directly proportional to exercise intensity
→ stimulates glycogenolysis
→ stimulates hormone sensitive lipase (increasing availability of free fatty acids (FFA) during exercise
HOWEVER at very high exercise intensity, there is vasoconstriction of vessels going to fat → less lipolysis
Insulin and exercise
Insulin → inhibit lipolysis at rest, but during exercise, insulin secretion falls → higher lipolytic activity
Adaptations with training (5)
can go backwards when you become inactive
1) Increased muscle mass
2) Increased mitochondrial content/oxidative capacity per gram of muscle
3) Increased intramuscular glycogen and triglyceride from increased turnover
4) Increased rates of lipolysis, beta oxidation and lactate clearance
5) Result is increased work capacity and shift to fat as the preferred fuel
People with diabetes, and inactivity results in __________ mitochondria and mitochondrial function
REDUCED
More mitochondria → increases insulin sensitivity in diabetic
–> exercise beneficial for diabetics (exercise also increases glucose transport into cell)
Training adaptations to substrate utilization: (3)
1) Decreased glycolytic flux at same relative intensities (decrease in glycogenolysis, lower glucose utilization)
- Reduced energy requirements derived from glucose
2) Lower blood lactate accumulation after training
3) Higher fat utilization: point you switch from fat oxidation back to glycolysis pushed farther out the more trained you are
Lower blood lactate accumulation after training
why?
1) Increased mitochondrial density → increased lactate clearing capacity
2) Increased MCT1 and MCT 4 expression for increased lactate transport
Metacarboxylates (MCTs)
specific lactate transporters, facilitate lactate transport in and out of muscle cell
MCT1 and MCT4
MCT1
oxidative muscle fibers (type I)
Transport inside cell and into mitochondria
Endurance training increases MCT1 expression → higher lactate clearance
MCT4
in glycolytic fibers (type II)
Lactate transport out of cell from glycolytic fibers to more oxidative fibers
Endurance training increases MCT4 expression → higher lactate transport to oxidative cells
Symptoms of Hypoglycemia
2 types of symptoms
ANS activation
Neuroglycopenic symptoms
*Can injure developing brain and result in permanent developmental problems
ANS activation symptoms of hypoglycemia
Sweating, shaking, trembling, tachycardia, anxiety, weakness, hunger, nausea, vomiting
Neuroglycopenic symptoms of hypoglycemia
Irritable, restless, headache, confusion, visual changes, slurred speech, impaired concentration, behavior changes, somnolence, coma/seizures
If hypoglycemia onset occurs after < 4-6 hours what are the possible causes? (4)
1) Glucose-6-Phosphatase deficiency
2) Glycogen storage diseases
3) Hyperinsulinism
4) Cortisol or GH deficiency in infants
If hypoglycemia onset occurs after >6-8 hours what are the possible causes? (4)
1) Cortisol and GH deficiency in infants, children, and adults
2) Fatty acid oxidation disorders in infants
3) Glycogen storage diseases
4) Gluconeogenic diseases
If hypoglycemia onset occurs after >10-12 hours what are the possible causes? (2)
1) Fatty acid oxidation disorders in older children and adults
2) Mild disorders of glycogen storage in adults
If hypoglycemia onset occurs after >12-24 hours what are the possible causes? (2)
1) Ketotic hypoglycemia (not actually a disorder, just when you are really skinny and don’t have lots of reserves)
2) Fatty acid oxidation disorders in older children and adults
If you are having problems with carbohydrate metabolism, but not fat metabolism what will be the clinical picture? (5 + possible precipitating events)
1) Ketones PRESENT (look at lower bicarb for ketones)
2) High uric acid → glucose trying to get out of liver
3) High triglycerides → glucose trying to get our of liver
4) Hypoglycemia
5) Accumulation of abnormal amounts of substrate behind block
Precipitating factors: fasting, illness, exercise, ingestion of dietary galactose or fructose
Glucose-6-Phosphatase deficiency: Von Gierke Disease
Most severe glycogen storage disease
Glucose enters liver normally, but cannot produce free glucose to leave liver → alternate pathways to get out
Lactate production, increased fatty acid synthesis (hypertriglyceridemia) and increased uric acid due to shunting and decreased renal excretion
Can make glycogen in liver, but cannot leave liver as glucose
→ Dramatic enlargement of liver (accumulation of NORMAL glycogen)
Presentation of Glucose-6-phosphatase deficiency (5)
infants within first year of life with SEVERE fasting hypoglycemia occurring within *3-4 hours after a meal
1) Enlargement of liver
2) Hypertriglyceridemia
3) Increased uric acid
4) Increased lactate production
5) Severe hypoglycemia
Treatment of Glucose-6-phosphatase deficiency
constant glucose supply
Glycogen synthase deficiency
cannot make glycogen, so nowhere to store glucose after a meal
Solely dependent on gluconeogenesis for glucose production
Glycogen synthase deficiency
presentation (2)
1) Hyperglycemia after a meal → fasting hypoglycemia
→ increased lactate, severe ketotic hypoglycemia
2) NO liver enlargement
Treatment of Glycogen synthase deficiency
high protein diet (gluconeogenic substrate) and low glycemic index carbs to minimize postprandial hyperglycemia
Branching enzyme deficiency
abnormal glycogen that is not branched
Accumulation in liver and skeletal muscle → tissue damage
Branching enzyme deficiency
presentation (5)
1) Hypoglycemia NOT a prominent symptom - TISSUE DAMAGE IS
2) Progressive liver cirrhosis, hepatosplenomegaly
3) Failure to thrive
4) Neonatal hypotonia and muscle weakness
5) Neuropathy
Glycogen phosphorylase deficiency and phosphorylase kinase deficiency:
Milder than G-6-phosphatase deficiency
Problem with glycogen breakdown
Gluconeogenesis, lipolysis, fatty acid oxidation, and ketogenesis intact
Glycogen phosphorylase deficiency and phosphorylase kinase deficiency:
presentation (4)
Ketotic hypoglycemia
Hepatomegaly
Short stature
Mild muscle weakness
Debranching enzyme deficiency (Cori Disease)
accumulation of abnormal glycogen in liver and muscle
problem with unbranching of stored, branched, glycogen
Debranching enzyme deficiency (Cori Disease)
Presentation:
Infants have ________ and ________ BUT their _______ and ________ levels are normal
Later in life, symptoms are milder and can be _________, _________, or ___________
Infants with hepatomegaly and hypoglycemia
-Lactate and uric acid levels normal
Later in life, symptoms are milder:
Hepatomegaly
Growth/short stature
Myopathy
Fructose-1,6-bisphosphatase deficiency
late hypoglycemia following fasting for 18-24 hours
Glycogen formation and breakdown are normal
Elevation of ketones during hypoglycemia (no defect in fat oxidation)
Can be precipitated by ingestion of fructose
Fructose-1,6-bisphosphatase deficiency
presentation (3)
1) Hypoglycemia (late and mild) - late hypoglycemia following fasting for 18-24 hours
2) Glycogen breakdown OK, no hepatomegaly
3) Elevated pyruvate → severe lactic acidosis → compensatory respiratory alkalosis (hyperventilation)
Fructose-1,6-bisphosphatase deficiency
treatment
give glucose through diet
Hereditary fructose intolerance mechanism
what accumulates? what does this accumulation inhibit?
Fructose → fructose-1-P by fructokinase → split into 3 carbon compounds by aldolase B → enter glycolysis/gluconeogenesis BELOW PFK1
Get accumulation of F-1-P → inhibits glycogenolysis and gluconeogenesis → hypoglycemia
Hereditary fructose intolerance mechanism
presentation (4)
Symptoms arise after fructose ingestion (e.g. fruit)
Nausea, vomiting, pallor, coma
Hypoglycemia
Hepatomegaly, elevated liver function tests (can progress to liver/kidney problems)
Galactosemia
mechanism
galactose → galactose-1-P → UDP-galactose → UDP glucose
Deficiency in enzyme that produces UDP galactose
Galactose-1-Phosphate Uridyltransferase (GALT)
Unable to metabolize galactose (e.g. from milk)
Galactosemia presentation
Early failure to thrive (vomiting with milk)
Hepatomegaly, cirrhosis
Cataracts, visual impairment (galactose in lens of eye)
Mental retardation
Neurologic problems (ataxia, tremor, speech impairment)
Treatment of galactosemia
lactose-free diet
Decreased fatty acid oxidation and ketone formation general presentation
1) Fasting hypoglycemia with LOW KETONES
2) Liver failure
3) Hypotonia
4) Coagulopathy
5) Hyperammonemia (increased AA breakdown)
6) Elevated CK (from exercise induced rhabdomyolysis)
Medium chain acyl CoA dehydrogenase deficiency (MCAD)
Unable to complete beta-oxidation for medium chain fatty acids
→ skeletal muscle increased reliance on glucose → increased peripheral glucose utilization
No energy from fatty acid oxidation for gluconeogenesis → reduced gluconeogenesis in liver
→ accumulation of carbon skeletons from gluconeogenic precursors → urinary organic acids
Reduced production of acetyl CoA by B-oxidation → failure to produce ketone bodies
Medium chain acyl CoA dehydrogenase deficiency (MCAD)
Presentation (6)
1) Infancy/early childhood - moderately severe hypoglycemia after 12-18 hours of fasting (especially with viral illness)
2) Abnormal urinary organic acids
3) Increase in acyl CoA derivatives in blood and urine
4) Decreased carnitine and increased acylcarnitines in blood
5) Hepatomegaly (fatty liver)
6) Hypoketotic hypoglycemia
MCAD treatment
avoid fasting, low fat, high carb diet
Very long chain acyl CoA dehydrogenase deficiency (VLCAD)
Similar phenotype to MCAD but may be milder and appear later in life
May get muscle soreness or rhabdomyolysis after exercise
CPT-1 Deficiency
carnitine problem
CPT-1 required to carry fatty acids into mitochondria where beta-oxidation takes place
No CPT-1 → defect in fat oxidation → fasting hypoglycemia with low levels of ketones
CPT-1 Deficiency presentation (3)
Presents in infancy following viral illness
Increased levels of free carnitine, low levels of acyl-carnitines
Elevated ammonia
Other medical causes of hypoglycemia (7)
1) Deficient counterregulatory hormones: glucagon, cortisol, growth hormone, or epinephrine deficient
2) Hyperinsulinism (transient, prolonged, permanent)
3) Ketotic hypoglycemia
4) Insulinoma
5) Insulin overdose
6) Sulfonylurea ingestion
7) Ethanol ingestion
___________ or __________ can cause counterregulatory hormone deficiency and hypoglycemia
hypopituitarism
adrenal insufficiency
Hypopituitarism
→ ACTH and/or GH deficiency
Midline defects, micropenis/undescended testes, jaundice, nystagmus, poor growth
Adrenal insufficiency
→ cortisol deficiency
Poor growth/weight, decreased energy, nausea, vomiting, abdominal pain, hypotension, salt craving, hyperpigmentation, other autoimmune diseases
Hyperinsulinism
possible causes
Transient, prolonged, or permanent
Causes: maternal diabetes, IV glucose given to mother during labor, perinatal stress, congenital hyperinsulinism
Infants of diabetic mothers
Large for gestational age (LGA) due to excessive maternal glucose and AA crossing placenta (maternal insulin does not) → EXCESSIVE INSULIN SECRETION by fetal pancreas in third trimester
→ HYPOGLYCEMIA after birth → excessive IV infusion required after birth and absence of ketones in blood
Ketotic hypoglycemia
Most common cause of hypoglycemia in childhood
Limited stores of muscle protein → cannot sustain normoglycemia from gluconeogenesis during periods of acute illness and reduced food intake
Ketotic hypoglycemia
presentation
Thin, undernourished (15 months - 5 years)
Enhanced ketone production (elevated serum/urine ketone)
“Grow out” of it as muscle mass increases and glucose utilization decreases
Insulinoma
tumor of endocrine pancreas
Condition of adults (not children)
Associated with Multiple Endocrine Neoplasia type I (MEN1)
High insulin + hypoglycemia + C-peptide + low ketones (insulin inhibits ketogenesis)
Insulin overdose
No serum c-peptide elevation with elevated insulin levels
Lab evaluation of hypoglycemia
obtain blood/urine BEFORE treatment has begun - “critical samples” collected at time of hypoglycemia
Increase risk of CVD with which lipid abnormalities?
- High LDL-C → biochemical modification and resultant inflammation and atherosclerosis → consistently increased risk of CVD
- High triglycerides:
- *NO evidence that lowering triglycerides improves CVD - Low HDL-C: linked to increased risk for CVD
- Increasing HDL with drugs has NO benefit for CVD - High Non-HDL-C:
Non HDL-Cholesterol =
Non HDL-Cholesterol = Total Cholesterol - HDL
a. Includes all apoB-100 containing lipoproteins (VLDL, IDL, LDL)
2. Thought to possibly be better predictor of ASCVD than LDL
Total cholesterol = ___ + ____ + _____
HDL + LDL + VLDL
Estimation of VLDL
When fasting, VLDL = TG/5 (as long as triglycerides are < 400 mg/dL)
Calculation of LDL-C
Friedewald Formula: LDL-C = Total cholesterol - HDL - TG/5
Risk factors for atherosclerotic events: (7)
- Age, males > females
- Caucasian vs. African American
- Higher total cholesterol
- Lower HDL
- Current cigarette smoking
- Systolic BP > 140 or anti-HTN medications
- Diabetes
Risk estimator
calculates score for 10-year ASCVD risk and Lifetime ASCVD risk
Causes of increased LDL
Increased LDL production or decreased catabolism
Increased LDL-C Production:
overproduction of VLDL by liver
E.g. insulin resistance
2 diseases that cause decreased LDL catabolism
- Familial hypercholesterolemia (FH)
2. Gain of function mutation in PCSK9
Familial hypercholesterolemia
AD absence/defectiveness of LDL receptor → LDL 2-3x normal in heterozygotes and 5-8x normal in homozygotes
PCSK9
regulator of LDL receptor degradation - PCSK9 binds LDL receptor and signals its degradation
Loss of function mutation in PCSK9
increased LDL receptor function, low LDL, reduced ASCVD
Gain of function mutation in PCSK9
clinical FH, reduced LDL receptor activity
Physical exam findings in hypercholesterolemia (3)
- Arcus cornealis: lipid deposits at limbus of cornea
- Xanthelasmas: lipid deposits in skin of eyelid
- Tendinous xanthomas: typically involves achilles tendons and extensor tendons of the hands
Normal tryglyceride level
Normal is < 150 mg/dL,
Triglyceride level 150-300 →
increased ASCVD
Triglyceride level 500-1000 →
clearance of chylomicrons approaches saturation
Triglyceride level > 1000 →
serum becomes lipemic
PE findings of high triglycerides (4)
- Lipemia retinalis: fatty serum in small vessels of retina
- Eruptive xanthomas: small yellowish papules on extensor surfaces of arms, abdomen, and back
- Hepatosplenomegaly (from triglyceride infiltration)
- Abdominal pain +/- acute pancreatitis
Increased VLDL production (4)
- Insulin resistance → increases in free fatty acid flux from adipose tissue
- Insulin is ANTI-lipolytic, so with insulin resistance more FFAs are released, go to liver, and increase hepatic VLDL synthesis and secretion - Drugs (See above)
- Alcohol: inhibits VLDL secretion, but enhances fatty acid production from ethanol → hypertriglyceridemia
- Genetics: Lipoprotein Lipase (LPL) and Apo A5 mutations
Decreased Triglyceride-Rich Lipoprotein Catabolism (4)
decrease lipoprotein triglyceride metabolism due to decreased lipoprotein lipase activity
1) Deficiency in LPL
2) Deficiency of Apo C2 (activator of LPL)
3) Deficiency in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (anchors LPL to endothelium)
4) Familial Dysbetalipoproteinemia:
Familial Dysbetalipoproteinemia
disturbances in IDL and remnant catabolism → increases in total cholesterol and triglycerides
Genetic variations in ApoE, ApoE2 isoform → defective binding of apoE2 to hepatic receptors that recognize VLDL and chylomicron remnants
Presentation of familial dysbetalipoproteinemia
plantas xanthomata, premature atherosclerosis
Causes of low HDL-C (4)
- Tangier disease
- Familial HDL deficiency
- LCAt deficiency
- Familial hypoalphalipoproteinemia
Tangier disease
genetic cause of HDL deficiency due to mutations in ATP binding cassette protein-1 (ABC-a1)
- Autosomal co-dominant
- Manifests as accumulation of cholesterol in peripheral organs with orange tonsils on exam
Familial HDL deciciency
genetic cause of HDL deficiency due to mutations in ATP binding cassette protein-1 (ABC-a1)
AD, not associated with systemic findings seen in Tangier disease
LCAt deficiency
homozygous mutations of LCAT gene → very low HDL levels
- Corneal opacities (fish eye syndrome)
- No increased ASCVD risk
Familial hypoalphalipoproteinemia
AD disorder, mutations in apoA1 gene
1.Linked to premature ASCVD
Apo(a)
apolipoprotein linked by a single disulfide bridge to LDL apoB → Lp(a)
- Increased Lp(a) linked with premature atherosclerosis (especially in women < 55yrs)
Mechanism of statins (3)
1) HMG CoA Reductase Inhibitors
2) Decrease hepatic pool of free cholesterol
3) Increase expression of LDL receptors on cell membranes
- (increasing uptake and catabolism of circulating LDL)
Effects of statins
First line, highly effective in lowering LDL and high intensity statin effective in lower triglycerides as well
6% rule and statins
Majority of LDL lowering comes from starting dose, and 6% reduction in LDL with each doubling of dose
Indications for statin therapy (4)
a. Secondary prevention (clinical ASCVD)
b. LDL >190, age > 21 years
c. Primary prevention - diabetes, age 40-75, LDL 70-189
d. Primary prevention - no diabetes, > 7.5% 10 year ASCVD risk, age 40-75 years, LDL 70-189
Side effects of statins (3)
higher risk of complications when combined with other lipid lowering agents (niacin, fibrates)
1) Myopathy: rhabdomyolysis, myositis (elevated CPK), myalgias
2) Abnormal AST and ALT
3) Associated with 10% increased risk of new-onset T2D
- Benefits highly outweigh this risk
3 Bile acid sequestrants
cholestyramine, colestipol, colesevelam
Mechanism of bile acid sequestrants
high molecular weight polymers that bind bile acids in intestine in exchange for a chloride ion
a. Neither absorbed nor metabolised
b. Reduce enterohepatic circulation of bile acids → increased LDL receptor expression in liver (use LDL to make bile acid)
Bile acid sequestrants lower LDL by ___%
10-30%
Statins lower LDL much more and have fewer adverse effects
Used as add on therapy, or if statin not tolerated
Side effects of bile acid sequestrants
- GI problems (nausea, bloating, constipation)
- Can also bind other drugs in gut (warfarin, thyroid hormone)
- Can raise TG by 5-30%
Ezetimibe mechanism
selectively inhibits cholesterol absorption at brush border
a.LDL lowering effect via increases in LDL receptor
Ezetimibe and statin
Improves outcomes by 20% when combined with statin
Side effects of ezetimibe (14)
NONE
Got ya!
Plant sterol and stanol esters
- No ASCVD data to support use
- No side effects
- Minimal LDL lowering
Mechanism of plant sterol and stanol esters
prevent mixed micelle formation in small intestine, partially reducing cholesterol absorption
2 PCSK9 inhibitors
alirocumab, evolocumab
PCSK9 inhibitors
- Injectable
- Lowers LDL by up to 60%
- Adjuncts to diet and max statin therapy for treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic CVD who require additional LDL lowering
3 classes of triglyceride lowering drugs
- Fibrates
- Fish oil
- Niacin
2 fibrates
gemfibrozil and fenofibrate
Fenofibrate
induces PPARa-related gene expression → increase intra hepatic fatty acid oxidation and reduce VLDL TG synthesis/secretion
Side effects of fenofibrate
Can raise creatinine (reversible when drug stopped)
When is gemfibrozil contraindicated
contraindicated when statins are coadministered due to higher risk of myopathy
a.Increased risk of cholelithiasis
Fish oils
high dose omega-3 fatty acids lower TG by 15-35%, and slightly increase HDL
- No evidence of educed ASCVD
- Only approved to treat patients with fasting TG > 500
Niacin
___ LDL
___ TG
___ HDL
lowers LDL
lowers TG
raises HDL
Niacin and statins
No additional benefit when used with statins
Side effects of niacin
flushing, rash, GI distress, hepatotoxicity, myopathy, glucose intolerance, hyperuricemia, gout
Primary treatment of elevated LDL-C and triglycerides
Statins
Secondary treatment of LDL-C and triglycerides
bile acid sequestrants, ezetimibe
- Can also consider fibrate and/or niacin
ii. **Combining classes has additive effects
Average kcal/kg/day
30 kcal/kg/day
KNOW HOW TO CALCULATE THIS STUFF
50kg woman x 30 kcal/kg/day = 1500 kcal/day
Traditional American diet consists of:
____% fat (____ % of this is SATURATED fat)
____% protein
_____% carbohydrate
33-37% fat, 50% of that is SATURATED fat
15% protein (animal)
48-52% carbohydrate
Biggest changes in american diet are: (4)
Increased omega-6 fat (corn oil)
Trans fat
Reduced whole grains and fiber
Increased total energy intake (calories), no fasting
Pool sizes of stored triglycerides
Adipose, liver/skeletal muscle
Adipose tissue: average person adipose tissue is 20-30% their body weight
- 70 kg person + 25% body fat → 18 kg of triglyceride x 9 kcal/g = 157,000 kcal stored energy
- 75 days of energy!
Liver and skeletal muscle: small amount of stored triglyceride, (hundreds of grams)
Distinguishing saturated and trans fats from unsaturated fats:
Saturated fats: form crystals at room temperature, and are therefore solid
Unsaturated fats: have cis double bonds and are typically liquid at room temp
EX) olive oil, nut oils, corn oil
Saturated fat:
Solid at room temp
Saturated and trans fats have adverse effects on CVD risk and increase risk for diabetes (promotes insulin resistance)
Monounsaturated fat
_______ is an example
benefits or adverse effects?
Oleic acid (C18 monounsaturated fat): olive oil, canola oil
May reduce risk for CVD, and have beneficial health effects
Omega-3 fat
(linolenic acid): fish and seafood, nut oils
Protect against diabetes
Omega-6 fat
(linoleic acid): vegetable and corn oils
Worse health effects than omega-3’s - associated with increased CVD risk
what is an example of a polyunsaturated fat
Fish oil DHA supplement
Trans fat
partially hydrogenated corn oil to generate double bonds in trans configuration → body may have trouble metabolizing these fats
Margarine, processed foods
Appear to have the most deleterious effects
Best diet or way to reduce CVD risk
- REDUCE positive energy balance
- Adherance to a diet whatever it is, is key
- most evidence is for low fat diet
- Good evidence for Mediterranean diet also
