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Chapter 24 Cholesterol,
Energy Balance
and Body
Temperature
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Metabolic Role of the Liver
• Hepatocytes
• ~500 metabolic functions
• Process nearly every class of nutrient
• Play major role in regulating plasma
cholesterol levels
• Store vitamins and minerals
• Metabolize alcohol, drugs, hormones, and
bilirubin
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Cholesterol • Structural basis of bile salts, steroid hormones,
and vitamin D
• Major component of plasma membranes
• 15% of blood cholesterol ingested; rest made in body, primarily liver
• Lost from body when catabolized or secreted in bile salts
• Part of hedgehog signaling molecule that directs embryonic development
• Transported in lipoprotein complexes containing triglycerides, phospholipids, cholesterol, and protein
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Lipoproteins
• Types of transport lipoproteins
• HDLs (high-density lipoproteins)
• Highest protein content
• LDLs (low-density lipoproteins)
• Cholesterol-rich
• VLDLs (very low-density lipoproteins)
• Mostly triglycerides
• Chylomicrons
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Figure 24.22 Approximate composition of lipoproteins that transport lipids in body fluids.
From intestine
80–95%
3–6%
2–7%
1–2%
Chylomicron
55–65%
Made by liver
10%
20%
45%
25%
LDL
Returned to
liver
5%
30%
20%
45–50%
HDL
15–20%
10–15%
5–10%
Triglyceride
Phospholipid
Cholesterol
Proteinl
VLDL
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Chylomicrons
• Mostly triglycerides
• Transport small lipids from small intestine, to
lymphatics and then to blood
• Lipoprotein lipase converts triglycerides to
fatty acids and glycerol to be used by tissues.
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Lipoproteins - VLDLs – the Necessary
• Source of VLDLs - liver
• transport triglycerides to peripheral tissues
(especially adipose)
• 85% of cholesterol is made in liver
• Liver coats cholesterol and triglycerides –
creates VLDLs
• See previous chart
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LDLs – The Bad
• VLDLs unload, they become LDLs
• Transport cholesterol to peripheral tissues for
membranes, storage, or hormone synthesis
• Excess LDLs are broken down, dumping
cholesterol into blood.
• Excess cholesterol picked up by HDLs and
transported to liver.
• What happens if too much cholesterol or too
few HDLs
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HDLs – The Good
• HDLs produced in liver
• HDLs transport excess cholesterol from
peripheral tissues to the liver
• Also serve the needs of steroid-producing
organs (ovaries and adrenal glands)
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Lipoproteins
• High levels of HDL are thought to protect
against heart attack
• High levels of LDL, especially lipoprotein (a)
increase the risk of heart attack
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Plasma Cholesterol Levels • The liver produces cholesterol
• At a basal level regardless of dietary cholesterol intake
• In response to saturated fatty acids
• Saturated fatty acids
• Stimulate liver synthesis of cholesterol
• Inhibit cholesterol excretion from the body
• Unsaturated fatty acids
• Enhance excretion of cholesterol
• Enhance cholesterol catabolism to bile salts
• Trans fats
• Increase LDLs and reduce HDLs
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Plasma Cholesterol Levels
• Unsaturated omega-3 fatty acids (found in
cold-water fish)
• Lower proportions of saturated fats and
cholesterol
• Make platelets less sticky help prevent
spontaneous clotting
• Antiarrhythmic effects on heart
• Lower blood pressure
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On a positive note…..
How to increase HDL and/or lower LDL
• Be female – let’s hear it for estrogen
• Exercise
• Use unsaturated oils
• Avoid smoking, caffeine and stress
• Avoid saturated fats and hydrogenated oils
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Non-Dietary Factors Affecting Cholesterol
• Body shape
• “Apple”: Fat carried on the upper body is correlated with high cholesterol and LDL levels
• “Pear”: Fat carried on the hips and thighs is correlated with lower cholesterol and LDL levels
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Recommended Total Cholesterol, HDL, and
LDL Levels
• Total cholesterol = 200 mg/dl or less
• Levels > 200 mg/dl linked to atherosclerosis
• High HDL thought to protect against heart
disease; >60 good;
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Homeostatic Imbalance
• Indicators for treatment
• LDL levels; assessments of cardiovascular
disease risk factors
• Previously used high cholesterol and
LDL:HDL ratios; not as reliable
• Statins
• Cholesterol-lowering drugs
• Estimated >10 million Americans take statins
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Energy Balance
• Bond energy released from food must equal the total energy output
• Energy intake = the energy liberated during food oxidation
• Energy output
• Immediately lost as heat (~60%)
• Used to do work (driven by ATP)
• Stored as fat or glycogen
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Regulation of Body Temperature
• Body temperature reflects the balance
between heat production and heat loss
• At rest, the liver, heart, brain, kidneys, and
endocrine organs generate most heat
• During exercise, heat production from skeletal
muscles increases dramatically
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Figure 24.24 Body temperature remains constant as long as heat production and heat loss are balanced.
Heat production Heat loss
• Basal metabolism
• Muscular activity
(shivering)
• Thyroxine and epinephrine (stimulating effects on metabolic rate)
• Temperature effect (warmer cells metabolize faster, producing more heat)
• Radiation
• Conduction/
convection
• Evaporation
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Core and Shell Temperature
• Core (organs within skull, thoracic & abdominal cavities) has highest temperature
• Rectal temperature best clinical indicator
• Core temperature regulated; fairly constant
• Blood - major agent of heat exchange between core and shell
• Shell (skin) – lowest temperature
• Fluctuates between 20C – 40C
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Role of the Hypothalamus
• Hypothalamus contains the two thermoregulatory
centers
• Heat-loss center
• Heat-promoting center
• The hypothalamus receives afferent input from
• Peripheral thermoreceptors in shell (skin)
• Central thermoreceptors (some in
hypothalamus) in core
• Initiates appropriate heat-loss and heat-
promoting activities
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Skin blood vessels dilate: capillaries become flushed with warm blood; heat radiates from skin surface
Activates heat-loss center in hypothalamus
Stimulus Increased body temperature; blood warmer than hypothalamic set point
Sweat glands secrete perspiration, which is vaporized by body heat, helping to cool the body
Body temperature decreases: blood temperature declines and hypothalamus heat-loss center “shuts off”
Homeostasis: Normal body temperature (35.8°C–38.2°C)
Figure 24.26 Mechanisms of body temperature regulation. (1 of 2)
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Figure 24.26 Mechanisms of body temperature regulation. (2 of 2)
Stimulus Decreased body temperature; blood cooler than hypothalamic set point
Body temperature increases: blood temperature rises and hypothalamus
heat-promoting center “shuts off”
Skeletal muscles activated when more heat must be generated; shivering begins
Activates heat- promoting center in hypothalamus
Skin blood vessels constrict, which diverts blood from skin capillaries to deeper tissues, minimizing overall heat loss
from skin surface
Homeostasis: Normal body temperature (35.8°C–38.2°C)
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Homeostatic Imbalance
• Heat exhaustion
• Heat-associated collapse after vigorous
exercise
• Due to dehydration and low blood pressure
• Heat-loss mechanisms still functional
• May progress to heat stroke if not cooled and
rehydrated promptly
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Homeostatic Imbalance
• Hyperthermia
• Elevated body temperature depresses
hypothalamus
• Positive-feedback mechanism (heat stroke)
begins at core temperature of 41C
increased temperatures
• Skin hot and dry; organs damaged
• Can be fatal if not corrected
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Homeostatic Imbalance
• Hypothermia
• Low body temperature from cold exposure
• Vital signs decrease
• Shivering stops at core temperature of
30 - 32C
• Can progress to coma and death by cardiac
arrest at ~ 21C
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Fever
• Controlled hyperthermia
• Due to infection (also cancer, allergies, or
CNS injuries)
• Macrophages release cytokines (formerly
pyrogens)
• Cause release of prostaglandins from
hypothalamus
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Regulation of Food Intake
• Arcuate nucleus (ARC), lateral hypothalamic
area (LHA), ventromedial nucleus (VMN) of
hypothalamus
• Release peptides influence feeding behavior
• Some ARC neurons neuropeptide Y (NPY)
and agouti-related peptides enhance appetite
• Other ARC neurons pro-opiomelanocortin
(POMC) and cocaine-/amphetamine-regulated
transcript (CART) suppress appetite
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Regulation of Food Intake – Short Term
• Feeding behavior and hunger regulated by
• Neural signals from digestive tract
• Bloodborne signals related to body energy stores
• Hormones
• To lesser extent, body temperature and psychological
factors
• Operate through brain thermoreceptors,
chemoreceptors, and others
• Food intake control short- or long-term
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Long-Term Regulation of Food Intake
• Leptin
• Hormone secreted by fat cells in response to
increased body fat mass
• Indicator of total energy stores in fat tissue
• Protects against weight loss in times of nutritional
deprivation
• Acts on the ARC neurons in the hypothalamus
• Suppresses the secretion of NPY, a potent appetite
stimulant
• Stimulates the expression of appetite suppressants
(e.g., CART peptides)
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Figure 24.23 Model for hypothalamic command of appetite and food intake.
Short-term controls
Stretch (distension of GI tract)
Glucose Amino acids Fatty acids
Insulin CCK
Vagal afferents
Nutrient signals
Gut hormones
Brain stem
Solitary nucleus
Long-term controls
Insulin (from pancreas)
Leptin (from lipid storage) Ghrelin
Glucagon Epinephrine
Gut hormones and others
Stimulates
Inhibits
POMC/ CART
neurons
ARC nucleus
NPY/ AgRP
neurons
Release melano- cortins
VMN (CRH-
releasing neurons)
Hypothalamus
Release CRH
LHA (orexin-
releasing neurons)
Release
NPY
Hunger (appetite enhancement)
Satiety (appetite suppression)
Release orexins
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Additional Factors in Regulation of Food Intake
• Temperature – cold activates hunger
• Stress – depends on individual
• Psychological factors
• Adenovirus infections
• Sleep deprivation
• Composition of gut bacteria
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