Chapter 24 Cholesterol, Energy Balance and Body Temperature. 10/28/13 MDufilho

Transcription

1 Chapter 24 Cholesterol, Energy Balance and Body Temperature 10/28/13 MDufilho 1

2 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 MDufilho 10/28/13 2

3 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 MDufilho 10/28/13 3

4 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 MDufilho 10/28/13 4

5 Figure Approximate composition of lipoproteins that transport lipids in body fluids. From intestine Made by liver 10% Returned to liver 5% 20% 30% 55 65% 80 95% 45% 20% 15 20% 45 50% 3 6% 2 7% 10 15% 5 10% 25% 1 2% Chylomicron VLDL LDL HDL Triglyceride Cholesterol Phospholipid Proteinl MDufilho 10/28/13 5

6 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. 10/28/13 6 MDufilho

7 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 10/28/13 7 MDufilho

8 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 10/28/13 8 MDufilho

9 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) 10/28/13 9 MDufilho

10 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 10/28/13 MDufilho 10

11 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 10/28/13 MDufilho 11

12 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 MDufilho 10/28/13 12

13 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 10/28/13 13 MDufilho

14 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 10/28/13 MDufilho 14

15 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; <40 not good High LDL cholesterol deposits in vessels; 100 or less good; 130 or above not good MDufilho 10/28/13 15

16 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 MDufilho 10/28/13 16

17 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 10/28/13 MDufilho 17

18 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 10/28/13 MDufilho 18

19 Figure 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 MDufilho 10/28/13 19

20 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 20 C 40 C MDufilho 10/28/13 20

21 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 heatpromoting activities 10/28/13 MDufilho 21

22 Figure Mechanisms of body temperature regulation. (1 of 2) 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) MDufilho 10/28/13 22

23 Figure Mechanisms of body temperature regulation. (2 of 2) Homeostasis: Normal body temperature (35.8 C 38.2 C) Stimulus Decreased body temperature; blood cooler than hypothalamic set point Body temperature increases: blood temperature rises and hypothalamus heat-promoting center shuts off Skin blood vessels constrict, which diverts blood from skin capillaries to deeper tissues, minimizing overall heat loss from skin surface Activates heatpromoting center in hypothalamus Skeletal muscles activated when more heat must be generated; shivering begins MDufilho 10/28/13 23

24 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 MDufilho 10/28/13 24

25 Homeostatic Imbalance Hyperthermia Elevated body temperature depresses hypothalamus Positive-feedback mechanism (heat stroke) begins at core temperature of 41 C increased temperatures Skin hot and dry; organs damaged Can be fatal if not corrected MDufilho 10/28/13 25

26 Homeostatic Imbalance Hypothermia Low body temperature from cold exposure Vital signs decrease Shivering stops at core temperature of C Can progress to coma and death by cardiac arrest at ~ 21 C MDufilho 10/28/13 26

27 Fever Controlled hyperthermia Due to infection (also cancer, allergies, or CNS injuries) Macrophages release cytokines (formerly pyrogens) Cause release of prostaglandins from hypothalamus MDufilho 10/28/13 27

28 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 MDufilho 10/28/13 28

29 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 MDufilho 10/28/13 29

30 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) 10/28/13 MDufilho 30

31 Figure Model for hypothalamic command of appetite and food intake. Short-term controls Long-term controls Stretch (distension of GI tract) Glucose Amino acids Fatty acids Vagal afferents Nutrient signals Brain stem Solitary nucleus POMC/ CART neurons Release melanocortins Hypothalamus VMN (CRHreleasing neurons) Release CRH Satiety (appetite suppression) Insulin CCK Ghrelin Glucagon Epinephrine Gut hormones Gut hormones and others Insulin (from pancreas) Leptin (from lipid storage) ARC nucleus Stimulates Inhibits NPY/ AgRP neurons Release NPY LHA (orexinreleasing neurons) Release orexins Hunger (appetite enhancement) MDufilho 10/28/13 31

32 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 MDufilho 10/28/13 32