Lipids: Chapter 6, McGuire

• Exam 2 covers Chapters 6, 7, and 8 of McGuire and all lectures since Exam 1, including the Obesity Explosion Book

Chapter 6: Lipids

• Fat contributes 35% of kcal intake (700 kcal out of 2000 kcal) in the current American diet
• Fat provides 9 kcal/gram
• 95% of dietary lipids are triglycerides (TAGs), containing 1 glycerol and 3 fatty acids per molecule
• Fatty acids bind to glycerol to form a triglyceride, a safe non-toxic form
• Free fatty acids resemble detergents and can solubilize cells/membranes if they build up too high
• Lipids resemble gasoline (medium to long hydrocarbons)
• Oleic acid is an 18-carbon monounsaturated fatty acid with 1 double bond, found in olive oil
• Saturated fats pack tightly and are often solid at room temperature like bacon, beef, or lamb fat
• Monounsaturated fats are liquid at room temperature, like olive oil
• Polyunsaturated fats have more than 1 double bond and are liquid at 32 degrees
• Saturated fatty acids, especially medium-chain ones in dairy, increase blood LDL cholesterol
• Cholesterol is a lipid in the steroid family, providing strength to plasma membranes and acts as a precursor for other molecules
• Cholesterol forms bile acids, which break up large fat droplets
• Palmitate from red meat is a saturated fatty acid
• Oleic acid from olive oil is a monounsaturated fatty acid
• Linoleic (n-6) from canola oil, soybean, and corn oil is an essential polyunsaturated fatty acid
• The body can make small amounts of arachidonic acid from linoleic (n-6)
• Linolenoic (n-3) from flaxseed and canola oil is an essential polyunsaturated fatty acid
• The body can make EPA & DHA from linolenoic (n-3) with very low efficiency
• Linoleic (n-6) and linolenoic (n-3) are essential fatty acids because the body cannot produce them
• The body can create arachidonic acid, EPA, and DHA from essential fatty acids, but with low efficiency, so dietary intake is important
• EPA & DHA are found in fish oil
• Omega 6 fatty acids, such as linoleic acid (18:2, ω-6), can be made into arachidonic acid (20:4)
• Omega 3 fatty acids, such as linolenic acid (18:3, ω-3), can be made into EPA and DHA, which are also found in fish oils

Dietary Fat Digestion & Transport

• Bile and bile acids reduce the size of lipid droplets and make them soluble
• Triglycerides are broken down in the intestinal lumen
• Chylomicrons carry only dietary fat and eventually reach the liver
• Once dietary triglycerides reach the liver cells, they are stored as TAGs, secreted as VLDL or oxidized for energy to CO2
• Cholesterol is found in the cell membrane to protect cells from damage
• Membrane composition is important for signaling receptors to function properly
• A high omega-6 polyunsaturated fat diet provides cells with omega-6 fatty acids and some arachidonic acid
• Arachidonic acid is needed in the brain but excess is harmful
• High arachidonic acid in phospholipids (PLs) triggers phospholipase A2 when the cell is damaged
• Phospholipase A2 breaks down PLs, releasing free arachidonic acid fatty acid molecules
• These molecules become eicosanoid signaling molecules and cause pain, stimulate immune cells, cause platelets to clot and activate repair mechanisms
• Cortisone inhibits phospholipase A2, slowing arachidonic acid release and decreasing inflammation
• Arachidonic acid is a major player in the inflammatory response
• Diseases related to the inflammatory response: coronary artery disease, asthma, inflammatory bowel disease
• Other possible diseases: osteoporosis, Alzheimer's disease, and severe COVID lung disease
• Omega 3 fatty acids make eicosanoid signaling molecules that counter the effects of arachidonic acid
• Omega 3 fatty acids are anti-inflammatory
• Consume fish twice a week or take a 1 gram fish oil capsule 2x per week to get enough omega 3s
• Canned Pacific salmon (ocean fish) is a good source of omega 3 fatty acids
• Recent epidemiology studies confirmed that PUFA intake is protective against chronic diseases
• Chylomicrons carry dietary lipids/fat and are made in the intestine
• VLDL carries endogenous lipids, made in the liver, carrying triacylglycerides (TAGs) throughout the body
• LDL is made in the blood from VLDL and carries cholesterol throughout the body
• LDL is known as bad cholesterol and causes plaque build-up
• HDL is made in the liver and intestine, using ApoA-1, and returns cholesterol to the liver
• HDL is known as good cholesterol

Adipose/Liver-Free Fatty Acid/VLDL Cycle (Dixon Cycle)

• This cycle involving endogenous fat is critical for survival
• Triglyceride (TAG) in the adipocyte (fat cell) breaks down into free fatty acids
• Free fatty acids diffuse into blood and bind to albumin
• Albumin carries free fatty acids throughout the body, especially to muscle
• The leftover free fatty acids are taken up by the liver and re-synthesized into TAGs
• Apolipoprotein B (ApoB) wraps around a triglyceride (TAG) and cholesterol lipid droplet to form VLDL
• The liver hepatocyte secretes VLDL into the blood
• More released fatty acids from adipose leads to more fatty acids taken up by the liver, more TAG synthesis, and more VLDL secretion
• VLDL delivers fatty acids to tissues like heart, muscle, and bone marrow
• Lipoprotein Lipase (LPL) on blood vessel endothelium catches VLDL particles and hydrolyzes fatty acids off the TAG molecule
• Remaining fatty acids in VLDL (in the form of TAG) are returned to tissues or adipose cells
• Tissues of the body have access to energy in the form of fatty acids
• Half of VLDL is converted to LDL (bad cholesterol)
• LPL may affect body shape (pear vs. apple)

Heart Attacks

• The heart has 3 main coronary arteries: right coronary artery, left anterior descending (LAD) coronary artery, and circumflex coronary artery
• Plaque can fill these arteries, which will block them completely and cause a major heart attack
• LDL particles are involved in plaque formation
• LDL particles get into the sub-endothelial space and get lodged there
• Macrophages gobble these LDL particles up and become foam cells
• The subendothelial space becomes filled with lipid, and smooth muscle cells start dividing and push out into the lumen of the artery
• A massive heart attack can occur when the artery is 50-60% blocked and a clot gets caught at the point of the plaque
• Statins inhibit something to do with artery inhibitors

Chapter 7: Metabolism

• Metabolism and production of Electrons – you are an electrical being
• ATP formation is a mechanical molecule
• Metabolism takes larger macronutrients and breaks them down to CO2 and H2O
• In the mitochondrion, hydrogens and electrons are borrowed and used to make ATP via the electron transport chain
• Complex life is chemiosmotic
• ATP is made from ADP in the mitochondrion
• Uncoupler proteins are important in Brown Adipose
• The Gate Keeper enzyme, Pyruvate Dehydrogenase, shuts off between meals
• Metabolism responds to starvation
• Cells handle macronutrients and turn them into energy; kcal is a kcal

Energy Production

• Glucose can be converted to fat and some non-essential amino acids
• Amino acids can be converted to fat and some can be made into glucose
• Fat can only be fat, and after starvation, it can be made into ketone bodies

Chapter 8: Energy Balance and Body Weight Regulation

• BMI is used in large population studies, but percent body fat is better
• Total energy expenditure (TEE) consists of basal metabolism + energy spent in movement + thermic effect of digestion
• About 60% of the energy consumed goes to Basal Metabolic Rate (BMR), and 40% goes to activities involving movement
• Of the 60% used for BMR, tissues use the following: brain, 20%; liver, 20%; muscle, 20%; heart, 10%; kidney, 5%; adipose, 3%; and other tissues, about 22%
• BMR can be estimated using 1 kcal/kg/hr for males or 0.9 kcal/kg/hr for females
• Thermic effect of food is about 5-10% of TEE
• TEE is measured by oxygen consumption
• Lower Kcal spent in NEAT (average about 2.5 hrs/day/person more in thin people) is an important cause of obesity in the US
• NEAT is energy spent in movement involved in everyday activities like walking, cleaning, light work, and even standing
• High-intensity exercise maintains heart muscle tissue, coronary artery smooth muscle cells, and lung capacity
• High-intensity exercise also stimulates fatty acid oxidation in muscle
• In the population, some people have a tendency to be heavy (thrifty (efficient) phenotype), and some people are thin (inefficient & fast-moving phenotype)
• Un-coupler proteins allow hydrogens to leak through inner membranes of the mitochondria, lowering ATP formation
• Body fat is dictated by genetics and environment
• Obesity (BMI ≥ 30) in the US is increasing due to food intake and lower activity levels (NEAT)
• Most worrisome is an increase in obesity in kids – about 17%

Hunger and Satiety

• Signals that regulate food intake are coordinated in the arcuate nucleus of the hypothalamus
• Signals are then sent to the nucleus accumbens, where dopamine is released
• Appetite has both physiological and psychological components
• Food intake is regulated by short-term signals, long-term signals and by basic neurochemistry and genetics
• Leptin is secreted by fat cells and indicates overall body fat amount
• Fat Signaling takes signals due to fat intake and digestion take about 30 – 45 minutes to work and can be confirmed by the Pizza Experiment

Basic System

• Oreo -> Various Body Signals -> Coordinate in Arcuate nucleus -> Endorphins secreted -> Go to Nucleus accumbens -> Dopamine is released -> Feeling of Satisfaction throughout the brain (love oreos!) -> The Prefrontal Cortex decides next action to be taken -> If enough feedback signals – You stop eating!
• Remember signals go to intestine via Vagus nerve and then satiety signals return to brain by several ways including Vagus nerve
• Body weights began to increase around 1980
• Calorie Intake increased about 280 Kcal per person per day
• Various Fats Increased – increased by about 250 Kcal per person per day since 1980 – Soy oil, shortening, and chicken fat were the main contributors

Classic Diets

• The Average American Diet consists of Calories: Carbohydrates: 50%; Fat: 35%; Protein: 15%
• Atkins diet is a Low Carb Diet! Less than 20 g of carbohydrate daily, with a gradual increase towards 50 g daily
• Calories Consist of : Carbohydrates: 5 - 10%; Fat: 65% (High Fat Diet); Protein: 25-30%
• Zone diet – Distribution of Calories: Carbohydrates: 40%; Fat: 30%; Protein: 30%
• Dean Ornish is a Vegetarian diet containing 10% of calories from fat
• Low Fat/ High Carb (Complex) Diet! Distribution of Calories: Carbohydrates: 70%; Fat: 10%; Protein: 20%
• Stanford Study indicates that most significant observation in the Gardiner Study was that: People that lost weight changed their lifestyle
• Economics and ability to change lifestyle were important aspects of successfully becoming more healthy
• Over 30 studies have shown that low carbohydrate diets (meaning high fat diets) are not better for losing weight on a consistent basis
• The Mediterranean Diet consists of Calories: Carbohydrates: 50%; Fat: 35%; Protein: 15%
• The Mediterranean Diet emphasizes whole grains (lots of fiber), nuts, many types of leafy greens, fruits, olive oil, fish and other sea food (calamari); Occasional meat, low in butter and milk