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Fat
This document discusses fatty acid metabolism in humans. It notes that virtually all fatty acids originate from dietary triglycerides, with long-term storage occurring in adipose tissue. Upper body subcutaneous fat accounts for the majority of systemic free fatty acid release, though intra-abdominal fat correlates with higher delivery of free fatty acids to the liver. High levels of free fatty acids can lead to insulin resistance, increased triglycerides, and vascular abnormalities.
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- 1. Fatty Acid Metabolismin Humans
- 2. Fat and LeanInteractions Lean Body Mass Adipose tissue
- 3. Fatty Acid Metabolismin Humans • Virtually all fatty acids originate from dietary triglyceride fatty acids. • Long-term storage site is adipose tissue. • Regulated release of fatty acids as free fatty acids provides the majority of lipid fuel for postabsorptive adults.
- 4. Fatty Acid Metabolismin Humans Oxidation 100 gm TG fatty acids Chylomicron TG 100 gm FFA Direct Oxidation CO2 + H2O (20-70 gm) Adipose tissue (30-80 gm) FFA: free fatty acids TG: triglycerides
- 5. Adipose Physiology Insulin Triglycerides Adipocyte FFA Glycerol FFA: free fatty acids
- 6. Adipose Physiology Insulin Triglycerides Adipocyte FFA Glycerol FFA: free fatty acids
- 7. Adipose Physiology Growthhormone catecholamines Triglycerides Adipocyte FFA Glycerol FFA: free fatty acids
- 8. Adipose Physiology Triglycerides Adipocyte FFA Glycerol Growth hormone catecholamines FFA: free fatty acids
- 9. Relationship Between BodyComposition and Physiological Consequences • Body fat distribution and free fatty acids (FFA) • Adipose tissue FFA release • Effects of excess FFA on health
- 10. Body Fat Distributionand Free Fatty Acids (FFA) Normal FFA High FFA
- 11. Intra-abdominal (Visceral) Fatand Upper Body Obesity Subcutaneous fat Intra-abdominal fat
- 12. Upper Body /Intra-abdominal (Visceral) Obesity and Insulin Resistance Muscle Vasculature FFA Insulin resistance Liver Pancreas Glucose release Constriction Relaxation Insulin secretion Upper body / Intra-abdominal obesity Insulin resistance
- 13. Free Fatty Acids(FFA) and Pancreas Insulin resistance FFA • Long-term damage to beta cells • Decreased insulin secretion Short-term stimulation of insulin secretion Pancreas Adipose tissue
- 14. Free Fatty Acids(FFA) and Dyslipidemia Liver Apo B100 synthesis and secretion Insulin resistance FFA VLDL-TG HDL cholesterol Adipose tissue TG: triglycerides
- 15. Free Fatty Acids(FFA) and Glucose Production Insulin resistance FFA Adipose tissue Liver Glucose release
- 16. Free Fatty Acids(FFA) and Muscle Insulin resistance Skeletal muscle cells Intra-muscular TG Glucose uptake Muscle Insulin resistance FFA Adipose tissue TG: triglycerides
- 17. Free Fatty Acids(FFA) and Hypertension Insulin resistance FFA Vasculature Constriction – greater response to alpha-adrenergic stimuli Relaxation – decreased nitric oxide generation Adipose tissue
- 18. Body Fat Distributionand Free Fatty Acids (FFA) • Upper body obesity is associated with adverse metabolic consequences. • Upper body obesity is associated with high basal and postprandial FFA. • Intra-abdominal (visceral) fat most strongly correlated with metabolic abnormalities. • Do the excess FFAs come from intra-abdominal fat?
- 19. Regional Adipose TissueModel Intra-abdominal (visceral) fat Lower body subcutaneous fat Upper body subcutaneous fat
- 20. Summary • Upperbody subcutaneous fat accounted for the majority of systemic free fatty acid (FFA) release. • Intra-abdominal (visceral) fat mass correlated with but was not the source of most systemic FFA release. • Intra-abdominal fat mass predicts greater delivery of FFA to the liver from intra-abdominal lipolysis. • A greater portion of free fatty acid (FFA) appearance derives from leg and splanchnic adipose tissue in obese than lean men and women.
- 21. Cont…. • Nevertheless,the majority of systemic FFAs originate from upper body subcutaneous fat in obese men and women. • Intra-abdominal (visceral) fat correlates positively with the proportion of hepatic FFA delivery from intra-abdominal fat in both men and women. • Upper body obesity is associated with high free fatty acids (FFA) due to excess release from upper body subcutaneous fat. • High FFA can result in: • insulin resistance in muscle and liver • VLDL TG • insulin secretion (?diabetes) • Vascular abnormalities
- 22. Conclusions • Inboth men and women, greater amounts of intra-abdominal (visceral) fat result in a greater proportion of hepatic free fatty acid (FFA) delivery originating from intra-abdominal adipose tissue lipolysis in the overnight postabsorptive state. • This implies that arterial FFA concentrations will underestimate hepatic FFA delivery systematically and progressively with greater degrees of intra-abdominal adiposity.
- 23. Cont… • Fatis a dynamic and varied tissue. • Regional differences in adipose biology affect health. • The causes of differences in body fat distribution are unknown. • The relative contributions of high free fatty acids and adipokines to adverse health is unknown.
- 24.
- 25. INTRODUCTION • HyperlipidemiaHyperlipoproteinemia means abnormally increased plasma lipoproteins-one of the risk factors for atherosclerosis (deposition of fats at walls of arteries, forming plaque) • Other risk factors-Cigarette smoking, Diabetes, another source of oxidative stress. Also, obesity and, hypertension. • Hyperlipemia denotes increased levels of triglycerides. • Such abnormality is extremely common in general population, regarded as highly modifiable risk factor for cardio vascular diseases, due to influence of cholesterol.
- 26. Plasma lipids include:cholesterols, triglycerides and phospholipids. Lipids are insoluble in plasma and are transported in protein capsule known as LIPOPROTEIN
- 27. Types of lipoproteins 1. Chylomicrons (TGs): → formed in GIT from dietary TG. 2. VLDL (TGs and cholesterol) → endogenously synthesized in liver. Degraded by LPL into free fatty acids (FFA) for storage in adipose tissue and for oxidation in tissues such as cardiac and skeletal muscle. 3. IDL (TGs, cholesterol); and LDL (cholesterol) → derived from VLDL hydrolysis by lipoprotein lipase. Normally, about 70% of LDL is removed from plasma by hepatocytes. 4. HDL (protective) →exert several anti atherogenic effects. They participate in retrieval of cholesterol from the artery wall and inhibit the oxidation of atherogenic lipoproteins& removes cholesterol from tissues to be degraded in liver. Composition Density Size Chylomicrons TG >> C, CE Low Large VLDL TG > CE IDL CE > TG LDL CE >> TG HDL CE > TG High Small
- 28. Causes of Hyperlipidemia • Diet • Hypothyroidism • Nephrotic syndrome • Anorexia nervosa • Obstructive liver disease • Obesity • Diabetes mellitus • Pregnancy • Obstructive liver disease • Acute heaptitis • AIDS (protease inhibitors)
- 29. Dietary sources ofCholesterol Type of Fat Main Source Effect on Cholesterol levels Monounsaturated Olives, olive oil, canola oil, peanut oil, cashews, almonds, peanuts and most other nuts; avocados Lowers LDL, Raises HDL Polyunsaturated Corn, soybean, safflower and cottonseed oil; fish Lowers LDL, Raises HDL Saturated Whole milk, butter, cheese, and ice cream; red meat; chocolate; coconuts, coconut milk, coconut oil , egg yolks, chicken skin Raises both LDL and HDL Trans Most margarines; vegetable shortening; partially hydrogenated vegetable oil; deep-fried chips; many fast foods; most commercial baked goods Raises LDL
- 30. Hereditary Causes ofHyperlipidemia • Familial Hypercholesterolemia • Codominant genetic disorder, Occurs in heterozygous form • Occurs in 1 in 500 individuals • Mutation in LDL receptor, resulting in elevated levels of LDL at birth and throughout life • High risk for atherosclerosis, tendon xanthomas (75% of patients), tuberous xanthomas and xanthelasmas of eyes. • Familial Combined Hyperlipidemia • Autosomal dominant • Increased secretions of VLDLs • Dysbetalipoproteinemia • Affects 1 in 10,000 • Results in apo E2, a binding-defective form of apoE (which usually plays important role in catabolism of chylomicron and VLDL) • Increased risk for atherosclerosis, peripheral vascular disease • Tuberous xanthomas, striae palmaris
- 32. Types of Hyperlipidemia FRERICKSON CLASSIFICATION- based on the pattern of lipoprotein on electrophoresis or ultracentrifugation. • Primary Chylomicronemia (I): Chylomicrons are not present in the serum of normal individuals who have fasted 10 hours. The recessive traits of deficiency of lipoprotein lipase or its cofactor are usually associated with severe lipemia. • Familial Hypercholesterolemia (IIA): Familial hypercholesterolemia is an autosomal dominant trait. Although levels of LDL tend to increase with normal VLDL. • Familial Combined (mixed) Hyperlipoproteinemia (IIB): elevated levels of VLDL, LDL. • Familial Dysbetalipoproteinemia (III): Increased IDL resulting increased TG and cholesterol levels. • Familial Hypertriglyceridemia (VI): Increase VLDL production with normal or decreased LDL. • Familial mixed hypertriglyceridemia (V): Serum VLDL and chylomicrons are increased
- 33. Diagnosis of hyperlipidemia • Diagnosis is typically based on medical history, physical examination and blood test done after overnight fasting.
- 34. Management of Hyperlipidemias I- Diet: • Avoid saturated fatty acids (animal fats) and give unsaturated fatty acids (plant fats). • - Regular consumption of fish oil which contains omega 3 fatty acids and vitamins E and C (antioxidants). II. Exercise: • - ↑ HDL and insulin sensitivity. III- Drug therapy: the primary goal of therapy is to decrease levels of LDL . Also,increase in HDL is recommended.
- 35. Medications for Hyperlipidemia Drug Class Agents Effects (% change) Side Effects HMG CoA reductase inhibitors Lovastatin Pravastatin LDL (18-55), HDL (5-15) Triglycerides (7-30) Myopathy, increased liver enzymes Cholesterol absorption inhibitor Ezetimibe LDL( 14-18), HDL (1-3) Triglyceride (2) Headache, GI distress Nicotinic Acid LDL (15-30), HDL (15-35) Triglyceride (20-50) Flushing, Hyperglycemia, Hyperuricemia, GI distress, hepatotoxicity Fibric Acids Gemfibrozil Fenofibrate LDL (5-20), HDL (10-20) Triglyceride (20-50) Dyspepsia, gallstones, myopathy Bile Acid sequestrants Cholestyramine LDL HDL No change in triglycerides GI distress, constipation, decreased absorption of other drugs
- 36. REFERENCE: K.D.Tripathi, Essentialsof Medical Pharmacology, 6th Edition, PgNo. 612-626. Goodman & Gilman’s, The Pharmacological Basis Of Therapeutics, 11th Edition, PgNo. 933-965. INTERNET.