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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

• Lowest density 10/28/13 4

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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)

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

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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