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Questions and Answers
What is the primary chemical structure of most dietary fats?
What is the primary chemical structure of most dietary fats?
Which type of dietary fat can be found in meat and dairy products?
Which type of dietary fat can be found in meat and dairy products?
Which process involves the extraction of energy from fatty-acids?
Which process involves the extraction of energy from fatty-acids?
What role do ketone bodies play in the body during fasting?
What role do ketone bodies play in the body during fasting?
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What is one of the functions of brown adipose tissue?
What is one of the functions of brown adipose tissue?
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In the fed state, which of the following occurs after lipid absorption?
In the fed state, which of the following occurs after lipid absorption?
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What dietary component primarily aids in the absorption of fat-soluble nutrients?
What dietary component primarily aids in the absorption of fat-soluble nutrients?
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What is a possible pathological condition linked to lipid metabolism?
What is a possible pathological condition linked to lipid metabolism?
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What is the primary storage form of energy in the body?
What is the primary storage form of energy in the body?
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What percentage of energy content do fatty acids contribute to triglycerides?
What percentage of energy content do fatty acids contribute to triglycerides?
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What is the role of apolipoproteins in lipoprotein metabolism?
What is the role of apolipoproteins in lipoprotein metabolism?
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What primarily drives the transport of triglycerides in the body?
What primarily drives the transport of triglycerides in the body?
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What components are primarily found in chylomicrons?
What components are primarily found in chylomicrons?
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Where does triglyceride resynthesis primarily occur after digestion?
Where does triglyceride resynthesis primarily occur after digestion?
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Chylomicrons enter the blood circulation through which structure?
Chylomicrons enter the blood circulation through which structure?
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What enzyme facilitates the interaction between chylomicrons and tissues for triglyceride utilization?
What enzyme facilitates the interaction between chylomicrons and tissues for triglyceride utilization?
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Which hormone primarily inhibits lipolysis by acting via receptor tyrosine kinases?
Which hormone primarily inhibits lipolysis by acting via receptor tyrosine kinases?
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What role do catecholamines and glucagon play during fasting or exercise states?
What role do catecholamines and glucagon play during fasting or exercise states?
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Which of the following hormones enhances the effects of catecholamines and glucagon by increasing HSL expression?
Which of the following hormones enhances the effects of catecholamines and glucagon by increasing HSL expression?
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During the fed state, what happens to triglycerides transported in chylomicrons?
During the fed state, what happens to triglycerides transported in chylomicrons?
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What is the primary outcome of β-oxidation in fatty acid metabolism?
What is the primary outcome of β-oxidation in fatty acid metabolism?
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What process occurs mainly in the mitochondria during fatty acid metabolism?
What process occurs mainly in the mitochondria during fatty acid metabolism?
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Which of the following statements about fatty acid activation in the cytosol is correct?
Which of the following statements about fatty acid activation in the cytosol is correct?
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What travels to the liver for further metabolism during lipolysis?
What travels to the liver for further metabolism during lipolysis?
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What is the primary function of brown adipose tissue (BAT)?
What is the primary function of brown adipose tissue (BAT)?
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What characterizes brown adipose tissue compared to white adipose tissue?
What characterizes brown adipose tissue compared to white adipose tissue?
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Which protein is primarily expressed in brown adipose tissue that uncouples oxidative phosphorylation?
Which protein is primarily expressed in brown adipose tissue that uncouples oxidative phosphorylation?
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What is a main clinical sign of Medium Chain Acyl-CoA Dehydrogenase deficiency (MCADD)?
What is a main clinical sign of Medium Chain Acyl-CoA Dehydrogenase deficiency (MCADD)?
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What happens due to a deficiency in Medium Chain Acyl-CoA Dehydrogenase?
What happens due to a deficiency in Medium Chain Acyl-CoA Dehydrogenase?
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What should be avoided to manage MCADD effectively?
What should be avoided to manage MCADD effectively?
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What is a common metabolic consequence of MCADD?
What is a common metabolic consequence of MCADD?
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Why is brown adipose tissue's expression of ATP synthase low?
Why is brown adipose tissue's expression of ATP synthase low?
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What must be present for acetyl CoA to enter the TCA cycle?
What must be present for acetyl CoA to enter the TCA cycle?
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What primarily triggers ketogenesis in the body?
What primarily triggers ketogenesis in the body?
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Which tissue is responsible for producing ketone bodies from acetyl CoA?
Which tissue is responsible for producing ketone bodies from acetyl CoA?
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What can lead to diabetic ketoacidosis?
What can lead to diabetic ketoacidosis?
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Which symptom is NOT typically associated with ketoacidosis?
Which symptom is NOT typically associated with ketoacidosis?
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What is the primary function of white adipose tissue (WAT)?
What is the primary function of white adipose tissue (WAT)?
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In which condition does ketogenesis occur besides fasting?
In which condition does ketogenesis occur besides fasting?
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What role does brown adipose tissue (BAT) play in the body?
What role does brown adipose tissue (BAT) play in the body?
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Which pathway is primarily responsible for triglyceride breakdown during fasting?
Which pathway is primarily responsible for triglyceride breakdown during fasting?
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What distinguishes the function of brown adipose tissue from white adipose tissue?
What distinguishes the function of brown adipose tissue from white adipose tissue?
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Which condition is associated with impaired fatty acid metabolism due to enzymatic deficiency?
Which condition is associated with impaired fatty acid metabolism due to enzymatic deficiency?
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During prolonged fasting, which process provides an alternative energy source for the body?
During prolonged fasting, which process provides an alternative energy source for the body?
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Which of the following is NOT a function of dietary fats in the body?
Which of the following is NOT a function of dietary fats in the body?
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What is the primary metabolic fate of triglycerides synthesized in adipose tissue during the fed state?
What is the primary metabolic fate of triglycerides synthesized in adipose tissue during the fed state?
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Which fatty acid metabolism process primarily occurs in the mitochondria?
Which fatty acid metabolism process primarily occurs in the mitochondria?
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What role does lipase play in the digestion of dietary fats?
What role does lipase play in the digestion of dietary fats?
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What is the effect of insulin on hormone-sensitive lipase (HSL)?
What is the effect of insulin on hormone-sensitive lipase (HSL)?
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Which of the following hormones acting on GsPCRs promotes lipolysis?
Which of the following hormones acting on GsPCRs promotes lipolysis?
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What is the process by which free fatty acids are mobilized from triglycerides during fasting?
What is the process by which free fatty acids are mobilized from triglycerides during fasting?
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During which metabolic state does hormone-sensitive lipase (HSL) become activated?
During which metabolic state does hormone-sensitive lipase (HSL) become activated?
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What is the primary location where beta-oxidation occurs?
What is the primary location where beta-oxidation occurs?
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Which substrate enters the TCA cycle after being produced by beta-oxidation?
Which substrate enters the TCA cycle after being produced by beta-oxidation?
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Which component is least involved in the structure of chylomicrons?
Which component is least involved in the structure of chylomicrons?
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What is the first step in the activation of fatty acids in the cytosol?
What is the first step in the activation of fatty acids in the cytosol?
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Which lipolytic hormone is responsible for enhancing the effects of catecholamines and glucagon?
Which lipolytic hormone is responsible for enhancing the effects of catecholamines and glucagon?
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Which statement accurately describes the role of apolipoproteins in lipoproteins?
Which statement accurately describes the role of apolipoproteins in lipoproteins?
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What forms the core of lipoproteins?
What forms the core of lipoproteins?
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How do lipoproteins differ in size and density?
How do lipoproteins differ in size and density?
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Which of the following best describes the absorption process of triglycerides?
Which of the following best describes the absorption process of triglycerides?
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What primarily triggers the secretion of chylomicrons into the lymphatic circulation?
What primarily triggers the secretion of chylomicrons into the lymphatic circulation?
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What is the primary fate of chylomicrons once they enter the bloodstream?
What is the primary fate of chylomicrons once they enter the bloodstream?
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Which molecule is NOT involved in the stabilization of lipoprotein particles?
Which molecule is NOT involved in the stabilization of lipoprotein particles?
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What condition can occur when glucose is unavailable and ketone levels become excessively high in the blood?
What condition can occur when glucose is unavailable and ketone levels become excessively high in the blood?
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Which of the following is a characteristic of ketogenesis?
Which of the following is a characteristic of ketogenesis?
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What is a primary consequence of oxaloacetate depletion during acetyl CoA metabolism?
What is a primary consequence of oxaloacetate depletion during acetyl CoA metabolism?
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What can lead to diabetic ketoacidosis aside from missed insulin treatments?
What can lead to diabetic ketoacidosis aside from missed insulin treatments?
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Which of the following tissues are primarily responsible for the uptake and utilization of ketone bodies?
Which of the following tissues are primarily responsible for the uptake and utilization of ketone bodies?
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What triggers the switch from glucose metabolism to gluconeogenesis?
What triggers the switch from glucose metabolism to gluconeogenesis?
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What effect does poorly managed diabetes have on ketone body metabolism?
What effect does poorly managed diabetes have on ketone body metabolism?
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What role does brown adipose tissue (BAT) play in lipid metabolism under cold conditions?
What role does brown adipose tissue (BAT) play in lipid metabolism under cold conditions?
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Which process must long chain fatty acids undergo to enter the mitochondrion?
Which process must long chain fatty acids undergo to enter the mitochondrion?
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What is the primary reason for the regulation of β-oxidation by Malonyl-CoA?
What is the primary reason for the regulation of β-oxidation by Malonyl-CoA?
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During β-oxidation, which of the following is a product generated in each cycle?
During β-oxidation, which of the following is a product generated in each cycle?
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Which ketone body is primarily formed from acetoacetate?
Which ketone body is primarily formed from acetoacetate?
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Which factor primarily influences the rate of fatty acid metabolism in tissues?
Which factor primarily influences the rate of fatty acid metabolism in tissues?
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What occurs when blood glucose levels decrease and glycogen is depleted?
What occurs when blood glucose levels decrease and glycogen is depleted?
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Which enzyme plays a crucial role in initiating the β-oxidation cycle?
Which enzyme plays a crucial role in initiating the β-oxidation cycle?
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What is the result of increased levels of insulin in relation to fatty acid metabolism?
What is the result of increased levels of insulin in relation to fatty acid metabolism?
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Study Notes
Dietary Lipids
- Dietary fats are composed of saturated, trans, and unsaturated fats.
- Most dietary fats have a similar chemical structure, consisting of three fatty acids attached to a glycerol backbone, known as a triglyceride or triacylglycerol.
- Dietary fats are an energy reserve, provide temperature control, protect internal organs, and aid in the absorption of fat-soluble vitamins.
Triglyceride (TG) Metabolism
- Triglycerides are the primary storage form of energy in the body and are stored in adipocytes.
- They contain twice the energy per gram compared to carbohydrates.
- Primarily composed of fatty acids (~95%) and glycerol (~5%).
- Triglycerides, due to their hydrophobic nature, are transported in lipoprotein particles.
Lipoproteins
- Lipoproteins are biochemical assemblies that transport lipid molecules in water.
- Consists of a TAG/cholesterol core surrounded by phospholipids, with hydrophilic portions facing outwards and lipophilic tails facing inwards.
- Apolipoprotein B48 is embedded in the outer shell for stability.
- Apolipoproteins play a structural role, act as ligands for lipoprotein receptors, and regulate enzymes in lipoprotein metabolism.
- Lipoprotein classes are categorized based on their size, lipid composition, and apolipoproteins.
- Size decreases and density increases as TAGs are removed.
Chylomicron Transport of Triglycerides
- Following digestion, fat is primarily absorbed as 2-monoacylglycerol and free FAs.
- Triglycerides are resynthesized in the endoplasmic reticulum and incorporated into chylomicrons in the Golgi apparatus.
- Cholesterol esters and fat-soluble vitamins are also incorporated into chylomicrons.
- Key apolipoproteins include ApoB, ApoC, and ApoE.
- Chylomicrons are secreted into the lymphatic circulation and enter the blood via the thoracic duct to the left subclavian vein.
Hormonal Regulation of Lipolysis
- Insulin, released in the fed state, inhibits HSL phosphorylation, thus inhibiting lipolysis.
- Catecholamines and glucagon, released in the fasted/exercise state, activate PKA, promoting HSL phosphorylation and lipolysis.
- Other lipolytic hormones, such as glucocorticoids, growth hormone, and thyroid hormone, enhance effects of catecholamines and glucagon by increasing HSL expression.
β-oxidation
- β-oxidation is the catabolic process by which FAs are broken down to generate energy.
- Occurs in most cell types, except erythrocytes and neurons.
- Enzymes are found within the mitochondria.
- β-oxidation is divided into three stages: activation of FAs in the cytosol, transport into the mitochondrion, and β-oxidation in the mitochondrial matrix.
- The process generates Acetyl-CoA, which enters the TCA cycle to produce ATP.
Ketogenesis
- Occurs when glucose is unavailable and oxaloacetate is depleted (e.g., fasting or diabetes).
- Acetyl-CoA enters ketogenesis in the liver and ketone bodies are released into the blood for target tissues.
- Ketone bodies are converted back to Acetyl-CoA for entry into the TCA cycle.
- The brain, heart, and muscle can utilize ketone bodies during fasting or diabetes.
Ketoacidosis
- Can occur with poorly managed diabetes or prolonged starvation.
- High levels of ketone bodies in the blood create acidosis.
- Occurs due to missed insulin treatments, malfunctions in insulin pumps, or illnesses that reduce insulin secretion.
- Symptoms include thirst, increased urination, abdominal pain, nausea, vomiting, dehydration, and confusion.
- Treatment involves insulin, fluids, and electrolyte replacement.
Brown Adipose Tissue (BAT)
- BAT is distinct to WAT and is activated in response to cold temperatures.
- Its primary function is thermogenesis, producing heat to maintain body temperature.
- Contains multiple lipid droplets, densely packed mitochondria, and is highly vascularized for oxygen supply.
- Has low levels of ATP synthase and expresses uncoupling protein 1 (UCP1), uncoupling oxidative phosphorylation and generating heat.
Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
- A rare disorder affecting β-oxidation and the breakdown of medium chain FAs into Acetyl-CoA.
- Caused by a genetic defect in Medium Chain Acyl Co-A Dehydrogenase, the first step in β-oxidation in the mitochondria.
- Clinical signs include intolerance to prolonged fasting, hypoglycaemia, impaired ketogenesis, and acidosis due to FA accumulation.
- Treatment is primarily preventive, avoiding fasting and using glucose supplements.
Dietary Fat
- There are three main types of dietary fats: saturated, trans, and unsaturated.
- Saturated fats are found in meat, butter, cheese, and chocolate.
- Trans fats are found in meat and dairy products.
- Unsaturated fats come from oils, avocados, nuts, and fish.
- Most dietary fats have a similar chemical structure: three fatty acids attached to a glycerol backbone.
- This is known as a triglyceride or triacylglycerol.
- Dietary fats are digested by lipase enzymes in the small intestine.
- Functions of dietary fat include:
- Energy reserve
- Temperature control
- Protection of internal organs
- Absorption of fat-soluble vitamins
Fast Fed Cycle
- The body cycles through fed and fasted states.
- In the fed state, nutrients are absorbed and stored.
- Triglycerides are synthesized and stored in adipose tissue.
- In the fasting state, the body uses stored energy and breaks down triglycerides, releasing free fatty acids.
- These fatty acids can be used for energy by beta-oxidation.
Triacylglycerides
- Triacylglycerides (TAGs) are made up of fatty acids and glycerol.
- They are stored in adipocytes and represent the main storage form of energy in the body.
- They contain twice the energy per gram compared to carbohydrates.
- Fatty acids make up 95% of their energy content, and glycerol makes up the remaining 5%.
Triglyceride Transport
- Triglycerides are large and hydrophobic molecules, meaning they are insoluble in water.
- To transport them, they are incorporated into lipoprotein particles.
- Lipoproteins are biochemical assemblies that transport lipids in water.
- They consist of a core of triglycerides and cholesterol, surrounded by an outer shell of phospholipids.
- The outer shell is amphiphilic, meaning it has both hydrophilic and lipophilic portions, allowing it to interact with water.
- Apolipoprotein (B48) is embedded in the outer shell to stabilize the complex.
- Apolipoproteins play three major roles:
- Structure: guiding the formation of lipoproteins
- Ligands: interacting with lipoprotein receptors
- Regulation: controlling enzymes involved in lipoprotein metabolism.
Classes of Lipoproteins
- Lipoproteins are classified based on their size, lipid composition, and apolipoproteins.
- There are several classes of lipoproteins.
- As triglycerides are removed, the size of the lipoprotein decreases, and the density increases.
Post-Absorption Transport of Triglyceride
- After digestion, fat is absorbed mainly as 2-monoacylglycerol and free fatty acids.
- Triglycerides are resynthesized in the endoplasmic reticulum.
- These re-synthesized triglycerides are incorporated into chylomicrons within the Golgi apparatus.
- This process also incorporates cholesterol esters and fat-soluble vitamins.
- Important apolipoproteins in chylomicrons are Apo B, Apo C, and Apo E.
Chylomicron Composition
- Chylomicrons consist of:
- Phospholipids
- Apolipoproteins (ApoB, ApoC, ApoE)
- Triglycerides (90%)
- Cholesterol esters
- Fat-soluble vitamins
Chylomicron Transport
- After synthesis, chylomicrons are secreted across the basolateral membrane.
- They enter the lymphatic circulation.
- They enter the blood via the thoracic duct to the left subclavian vein.
Lipoprotein Lipase & Lipogenesis
- Chylomicrons circulate in the blood until they encounter organs expressing the enzyme lipoprotein lipase (LPL).
Hormonal Regulation of Lipolysis
- The primary hormones that regulate lipolysis are insulin, catecholamines, and glucagon.
- Insulin:
- Released in the fed state.
- Acts on a receptor tyrosine kinase.
- Inhibits HSL phosphorylation, which inhibits lipolysis.
- Catecholamines and Glucagon:
- Released in the fasted or exercise state.
- Act on GsPCRs.
- Elevates cAMP levels and activates PKA.
- Promotes HSL phosphorylation, which promotes lipolysis (breakdown of fat).
- Other lipolytic hormones, such as glucocorticoids, growth hormone, and thyroid hormone, work by increasing the expression of HSL, enhancing the effects of catecholamines and glucagon.
Summary of the Fed and Fasting States
- Fed state (high insulin levels):
- Triglycerides are transported in chylomicrons to adipose tissue.
- Chylomicrons bind via ApoC to LPL.
- LPL breaks down triglycerides into monoacylglycerol and free fatty acids.
- These molecules diffuse into adipocytes and are reassembled into triglycerides, stored in fat droplets as energy reserves.
- Fasting state or exercise (low insulin and high glucagon/catecholamine levels):
- HSL (and other lipases) become phosphorylated and activated.
- Triglycerides are metabolized into free fatty acids and glycerol.
- Free fatty acids bind to albumin and travel to their target tissue for further metabolism.
- Glycerol travels to the liver for further metabolism (glycolysis or gluconeogenesis).
- Energy is released.
Extraction of Energy from Fatty Acids: Beta-oxidation
- Beta-oxidation is the catabolic process where fatty acids are broken down to generate energy.
- This process occurs in almost all cell types, excluding erythrocytes and neurons.
- Beta-oxidation enzymes are found in the mitochondria.
- It occurs in three stages:
- Activation of fatty acids in the cytosol.
- Transport into the mitochondrion.
- Beta-oxidation in the mitochondrial matrix.
- The overall process involves breaking down fatty acid chains into acetyl-CoA, which enters the TCA cycle to produce energy.
Step 1: Activation of Fatty Acids
- When fatty acids enter the cytosol, they are activated to acyl-CoA by acyl-CoA synthase (thiokinase).
- Short-chain fatty acyl-CoA can diffuse directly into the mitochondrion.
- Long-chain fatty acids cannot diffuse and must use the carnitine shuttle.
Step 2: Transport to the Mitochondrion: The Carnitine Shuttle
- Carnitine palmitoyl transferase I (CPT I) substitutes carnitine for CoA on the fatty acid.
- Acyl-carnitine crosses the inner mitochondrial membrane (IMM) into the matrix via acyl-carnitine translocase.
- Carnitine palmitoyl transferase II (CPT II) resubstitutes CoA for carnitine, regenerating acyl-CoA.
- Carnitine exits the matrix through the translocase into the intermembrane space.
Step 3: Beta-oxidation in the Mitochondrial Matrix
- A cyclic 4-step reaction initiated by acyl-CoA dehydrogenase.
- Three isoforms of acyl-CoA dehydrogenase exist: short-chain, medium-chain, and long-chain.
- With each cycle, two carbons are removed from the fatty acid as acetyl-CoA.
- Each cycle produces:
- Acetyl-CoA, which enters the TCA cycle/ETC to generate ATP.
- 1 NADH, which enters the ETC to generate ATP.
- 1 FADH2, which enters the ETC to generate ATP.
Regulation of Beta-oxidation
- The rate of beta-oxidation is largely regulated by:
- Levels of free fatty acids: Metabolism of fatty acids by tissues is proportional to levels of plasma free fatty acids, which are dependent on the activity of HSL in adipose tissue and levels of insulin (inhibitory) and glucagon/catecholamines (stimulatory).
- Levels of cytosolic malonyl-CoA (fatty acid biosynthesis): The first step in fatty acid biosynthesis is the generation of malonyl-CoA in the cytoplasm. Malonyl-CoA inhibits CPT1, preventing fatty acids from entering the mitochondria. This ensures that fatty acid biosynthesis and breakdown do not occur simultaneously.
Ketone Bodies
- Ketone bodies serve as a reserve fuel in the body, especially for the brain.
- There are three ketone bodies:
- Acetoacetate
- Beta-hydroxybutyrate (formed from acetoacetate)
- Acetone (formed in small amounts by decarboxylation of acetoacetate)
- Ketone bodies are synthesized only in the liver from acetyl-CoA.
Ketogenesis
- Ketogenesis occurs in response to unavailability of blood glucose (e.g., fasting).
- When blood glucose levels decrease and glycogen stores are depleted, the body switches to lipid metabolism.
- Acetyl-CoA enters the TCA cycle to produce energy, but oxaloacetate is required.
- When glucose levels are low, the body also utilizes oxaloacetate for gluconeogenesis.
- When oxaloacetate is depleted, acetyl-CoA cannot enter the TCA cycle and is used to form ketone bodies, known as ketogenesis.
- Ketogenesis also occurs in diabetes mellitus since cells cannot properly metabolize glucose.
Ketogenesis Pathway
- Ketogenesis occurs when glucose is unavailable and oxaloacetate is depleted (e.g., fasting or diabetes).
- Acetyl-CoA enters the ketogenesis pathway in the liver.
- Ketone bodies are released into the blood.
- They are taken up into target tissues (brain, heart, muscle).
- They are converted back into acetyl-CoA, which then enters the TCA cycle.
Ketoacidosis
- Under poorly managed diabetes or prolonged starvation, ketones become an important energy source.
- However, if ketone levels in the blood become too high, ketoacidosis can occur because acetoacetate and beta-hydroxybutyrate are acids.
- Diabetic ketoacidosis can happen due to:
- Missed insulin treatments or malfunctioning pumps.
- Illnesses releasing hormones that reduce insulin secretion (e.g., pneumonia, infection).
- Symptoms of ketoacidosis include thirst, increased urination, abdominal pain, nausea, vomiting, dehydration, and confusion.
- Ketoacidosis can be fatal if not managed.
- Treatment involves insulin, fluids, and electrolytes.
Brown Adipose Tissue (BAT)
- White adipose tissue (WAT) comprises most of the body's fat stores. It serves as the primary reservoir for storing and releasing fatty acids to generate energy.
- Brown adipose tissue (BAT) is distinct from WAT and is activated in response to cold temperatures. It plays a crucial role in regulating body temperature.
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Description
This quiz covers the fundamentals of dietary lipids, including their types and structures, and their roles in energy storage and vitamin absorption. It explores triglyceride metabolism, energy storage, and the function of lipoproteins in lipid transport. Test your knowledge on these essential biochemical concepts.