Obesity notes

What is our only source of energy for performing biological work

the food we eat. the primary macromolecules we ingest, absorb and use are carbohydrates, proteins and lipids

What are the three major metabolic destinations (fates) for the principle nutrients

• they will be used for energy for active processes

• synthesized into structual or functional molecules

• synthesized as fat or glycogen for later use as energy

What is energy stored in

Fat and glycogen

Where is glycogen stored (glucose polymer) 

in liver and skeletal muscles 

What is compact storage

Fat

Fats have more than twice the energy content of an equal amount of ___

carbohydrate or protein

energy in fats is ___

harder and slower to access

The most vital liver functions are 

protein metabolism

Demaination liver function

removes NH2 (amine group) from amino acids so cells can use what is left as energy source

Converts resulting toxic ammonia (NH3) into ___ for excretion by the kidney (liver function) 

urea

Synthesizes ___ utilized in the clotting mechanism and immune system (liver function)

plasma proteins

Converts one ___ into another (liver function)

amino acid

Carbohydrate metabolism 

• turns proteins into glucese

• turns triglycerides into glucose

• turns excess glucose into glycogen and store in the liver

• breaks down glycogen back into glucose as needed 

lipid metabolism

• synthesize cholesterol and phospholipids

• synthesize lipoproteins — HDL and LDL (used to transport fatty acids in bloodstream)

• stores some fat

• oxidizes (breaks down) fatty acids

• converts carbohydrates and proteins into fats

Other metabolic activities, include:

• produces bile (waste products of RBCs and enzymes that break down fats)

• stores glycogen, iron and vitamins A, D, and B12

• Phagocytosis of worn out RBCs and foreign substances

• removes toxins such as alcohol and certain drugs from the blood

Lipid metabolism is key for

long-term energy storage and release

Lipids

nonpolar, hydrophobic and do not dissolve in watery blood. Cholesterol metabolism and regulation of blood cholesterol levels

Cholesterol 

required as a component of the plasma membrane; it is a precursor molecule for other steroid hormones, bile salts and vitamin D 

Two sources of cholesterol in the body:

1. Liver synthesis - we make all of the cholesterol we need

2. The food we eat

What are blood levels of cholesterol regulated through?

partly through negative feedback, and a high intake of cholesterol will somewhat inhibit cholesterol synthesis by the liver

diets high in saturated fats ___ 

stimulate liver synthesis of cholesterol and reduce its elimination from the body, while unsaturated fatty acids enhance excretion of cholesterol to bile for removal from the body 

Trans fats

unsaturated fats that have been modified to make them more solid and have a worse effect on blood cholesterol than saturated fats, causing a greater increase in LDLs, and a greater reduction in HDLs 

How are most lipids transported in the blood

in combination with proteins as lipoproteins, which solubilize lipids and regulate entry and exit at specific target cells

What do all lipoproteins contain

they vary in the percentage of lipid they contain, but all contain triglycerides, phospholipids, and cholesterol, in addition to protein

The greater the proportion of lipid in the lipoprotein ____

the lowers its density, there are VDLs, LDLs,and HDLs

VLDLs

very-low-density lipoproteins

LDLs

low-density lipoproteins 

HDLs

high-density lipoproteins

Where are chylomicrons formed

small intestine mucosal epithelial cells

Chylomicron function 

transport dietary lipids to adipose tissue where their fatty acids are released and stored in the adipocytes and used by muscle cells for ATP 

What are Chylomicron remnants

intermediate-density lipoproteins (IDLs)

What do IDLs become

LDLs

Where are VLDLs formed 

in hepatocytes 

VLDL function

transport triglycerides synthesized in hepatocytes to adipocytes for storage

What are VLDLs converted to

LDLs

LDLs are considered

“bad” cholesterol

LDLs function

• carry 75% of total cholesterol in blood

• deliver cholesterol to body cells for repair and synthesis

• receptors are necessary for the liver to take them up

• some are taken up by scavenger cells like macrophages

When present in excessive numbers, LDLs ___ 

deposit cholesterol in and around smooth muscle fibers in arteries = fatty plaques 

What are HDLs considered

“good” cholesterol

Where are HDLs made

the liver

HDLs function

remove excess cholesterol from body cells and blood and transport it to liver for elimination and provide cholesterol to steroid-producing organs

High levels of HDL are considered _____ 

beneficial, as the cholesterol they contain is bound for removal, but high levels of lDL are considered a risk, because the cholesterol they contain may be laid down on vessel walls, forming plaques. 

Desirable level of TC (total cholesterol)

less than 200 mg/dl

Desirable level of LDL

less than 130 mg/dL

Desirable level of HDL

greater than 40 mg/dL

Desirable level of triglycerides 

10-190 mg/dl 

Lipids in foods are

phospholipids, cholesterol and most commonly, fats (triglycerides)

Lyposis

lipds are oxidized for energy

Lipds are stored in adipose tissue as triglycerides mostly in the subcutaneous layer. 

50% subcutanceous, 12% near kidneys, 15% in omenta, 15% in genital area, 8% between muscles 

Adipose cells contain _____

lipases that catalyze the deposition of fats from chlyomicrons and hydrolyze neutral fats into fatty acids and glycerol.

Are fats in adipose tissue inert?

No, they are catabolized and mobilized constantly throughout the body

Triglycerides are stored primarily in ___

the bodys adipocytes, where a given molecule may remain for 2 to 3 weeks, with continual turnover.

Triglycerides are split into ___ through a process called ___ 

fatty acids and glycerol, lipolysis

triglyverides are split under the influence of hormones such as

epinephrine, noepinephrine and glucocorticoids and released from fat deposits. Glycerol and fatty acids are then catabolzied separtely

Glycerol can be converted into

glucose and enter glycolysis

In beta oxidation, 

carbon atoms are removed in pairs from fatty acid chains. The resulting molecules of acetyl coenzyme A enter the Krebs cycle 

As a part of normal fatty acid catabolism two acetyl coA molecules can form three ketone bodies

acetoacetic acid which can then be converted to beta-hydroxybutyric acid and acetone

Ketosis

an excess of ketone bodies

What might ketosis cause 

acidosis or abnormally low blood pH - a big problem with diabetics 

There is a continuous turnover of triglycerides in

adipose tissue.

New fats are stored for later use, and

stored fats are broken down and released to the blood

Glyercol and fatty acids from dietary fats not immediately needed for energy are what 

recombined into triglycerides and stored. 50% winds up in subcutaneous tissue

Lipogenesis

the conversion of glucose or amino acids into lipids

When excess ATP and glucose levels are high,

there is an excess of Acetyl coA which can form triglycerides and the glucose is converted to glycerol. This makes triglycerides that are stored in fat.

Therefore, even with a low-fat diet, carbohydrate intake can provide all the raw materials needed to make triglycerides (fat). The process is stimulated by insulin

Lipids are also used as structural molecules or to synthesize essential molecules. What are some examples? 

• phospholipids of plasma membranes 

• lipoproteins that transport cholesterol

• thromboplastin for blood clotting 

• myelin sheaths to speed up nerve conduction

• cholesterol used to synthesis bile salts and steroid hormones 

What is energy homeostasis regulated by

the brain, gastointenstinal tract, other systems and adipose tissue

The purpose of energy homeostasis

controlling food intake, satiety, and energy expenditure. Processes involve a variety of chemical mediators in central and peripheral neurochemical pathways

Adipose tissue function 

provides insulation, mechanical support, secretes hormonelike signaling molecules known as adipokines, and contributes to immune cell function. It is the bodys major energy reserve to fuel other tissues. 

Adipocytes

fat-storing cells that store calories as triglycerides, synthesize triglycerides from glucose and mobilize energy in the form of free fatty acids and glycerol

White adipose tissue is found where

in viscera, muscle, bone marrow and subcutaneously.

What does white adipose tissue contain 

macrophages, mast cells, neutrophils, fibroblasts, and blood vessels and nerves 

Adipocytes contain

one large fat droplet of triglyceride

White adipose tissue function

release FFAs and glycerol in low nutritional state under the direction of epi and norepi. FFAs and glycerol can be used for ATP prodcution

Subcutaneous fat 

higher leptin, lower adiponectin, lower inflammatory cytokines and lower insulin resistance. New fat cells (hyperplasia) form and have a greater fat storage capacity. 

expansions of this fat tissue has fewer complications with obesity 

Visceral fat

located around organs. storage is by adipocyte hypertrophy, and stores triglycerides as VLDLs. This fat is more hormonally active and releases leptin and inflammatory mediators

Excess visceral fat is assocaited with

impaired lipid and glucose metabolism insulin resistance, metabolic syndrome and an increased risk of cardiovascular disease and cancer.

estrogen and estrogen receptors ___ 

enhance deposition of white fat and subcutaneous tissue and inhibit it in visceral tissue 

Excessive bone marrow adipose tissue is associated with what

osteoporosis and alters hematopoiesis

Brown adipose tissue (BAT)

cells derive from muscle tissue and have multiple lipid droplets. Have lots of mitochondria which is what makes it this color.

BAT function

can generate heat rapidly via oxidation of triglycerides - SNS and T3 stimulation - non-shivering heat 

Where is BAT commonly found

in lean adults: in neck, supraclavicular, axillary and paravetebral and perirenal regions.

What does the down color of adipose tissue do

protects against obesity and metabolic syndrome

Beige fat 

Subpopulation of white adipocytes that also have mitochondria 

When does beige fat develop

with chronic exposure to cold and exercise, and disappears with elevated ambient temperatures. Diminished in obesity

What two things together promote BAT, increasing energy and expenditure and weight loss

Leptin and Insulin

What is regulation of food uptake controlled by 

central and peripheral physiological signals 

What is appetite controlled by

arcuate nucleus (ARC) of hypothalamus: balances opposing effects of neurons

Appetite is stimulated by what

acitivation of orexigenic (appetite stimulating) neurons that stimulate eating and decrease metabolism (anabolic)

What is appetite inhibited by 

anorexigenic (appetite depressing) neurons that suppress appetite, inhibit eating and increase metabolism 

What controls hunger and satiety

Neural afferents and hormonal signals from GI tract

Obesity

a metabolic disorder with an increase in body fat mass and a body mass index (BMI) greater than 30 in adults and greater than the 95th percentile in growth charts in children

Body mass index (BMI) 

Ratio of weight to height calculated by diving weight (kilograms) by the square of one’s height (meters) and used as an indicator of body mass statue (underweight, normal, obese) 

What is obesity conceptually defind as

an excess of body fat and clinically defined by the BMI

Normal BMI

18.5-24.9

Overweight BMI 

25.0-29.9 

Obese BMI

less than or equal to 30.0

What BMI is considered extreme or morbid obesity

BMI above 40 kg.m²

What is the fifth leading cause of death in the US 

obesity 

Three leading causes of death are associated with obesity

cardiovascular disease, type 2 diabetes mellitus and cancer

When does obesity develop

when caloric intake exceeds caloric expenidenture in genetically susceptible people