Triacylglycerol And Adipose tissue Metabolism
Metabolism of Triacylglycerol
Triacylglycerols are synthesized mainly in liver, adipose tissue and intestinal cells.
There are two pathways:
- The general pathway, which is operational in liver, adipose tissue and other organs where fatty acids synthesis occur
- The intestinal pathway, which is responsible for resynthesis of TAG following digestion and absorption of dietary fats.
Glycerol-3-Phosphate serves as the primary starting material and phosphatidic acid is the key intermediate of the pathway which proceeds in the following steps:
- Synthesis of phosphatidic acid from glycerol-3-phosphate and fatty acyl CoA
- Synthesis of triacylglycerol from phosphatidic acid
Hydrolysis of Triacylglycerols (Lipolysis)
- Lipases are the enzymes involved in degradation of triacylglycerol, catalyzing sequential removal of the fatty acids from glycerol backbone.
- Various types of lipases are known, most important of which are hormone-sensitive lipase, lipoprotein lipase and hepatic lipase.
Hormone sensitive lipase (HSL)
- Acts on triacylglycerol stores in adipose tissue
- Catalyzing the first cleavage to remove the fatty acid esterified to C-1 of glycerol.
- Lipases specific for MAG and DAG then cleave the fatty acids linked to C-2 and C-3.
Lipoprotein Lipase (LPL)
- Causes hydrolysis of triacylglycerols present in some lipoproteins (VLDL and chylomicrons)
- Thus required for utilization of circulating TG.
- This enzyme is synthesized in adipose tissue, skeletal muscle, the myocardium, the lactating mammary gland, spleen, lung, kidney and aorta.
- VLDL and chylomicrons passes through the capillaries of these organs, they bind to LPL and their TG is hydrolyzed to free fatty acids and 2-MAG.
- Hydrolyzes TG present in other lipoprotein fractions e.g., Intermediate and high-density lipoproteins.
METABOLISM OF ADIPOSE TISSUE
Adipose Tissue in Well-fed Condition•
- Active lipogenesis occurs in the adipose tissue.
- The dietary triglycerides transported by chylomicrons and the endogenously synthesized triglycerides from liver brought by VLDL are both taken up by adipose tissue and esterified and stored as TAG.
- The lipoprotein molecules are broken down by the lipoprotein lipase present on the capillary wall.
- In well-fed condition, glucose and insulin levels are increased. GluT4 in adipose tissue is insulin dependent. Insulin increases the activity of key glycolytic enzymes as well as pyruvate dehydrogenase, acetyl CoA carboxylase and glycerol phosphate acyl transferase. The stimulant effect of insulin on the uptake of glucose by adipose tissue, on the glycolysis and on the utilisation of glucose by HMP pathway also enhances lipogenesis.
- Insulin also causes inhibition of hormone sensitive lipase, and so lipolysis is decreased.
Adipose Tissue in Fasting condition
- The metabolic pattern totally changes under conditions of fasting. TAG from the adipose tissue is mobilized under the effect of the hormones, glucagon and epinephrine.
- The cyclic AMP mediated activation cascade enhances the intracellular hormone sensitive lipase. The phosphorylated form of the enzyme is active which acts on TAG and liberates fatty acids.
- Under conditions of starvation, a high glucagon, ACTH, glucocorticoids and thyroxine have lipolytic effect. The released free fatty acids (FFA) are taken up by peripheral tissues as a fuel.
Adipose Tissue and Diabetes Mellitus
- Lipolysis is enhanced and high FFA level in plasma is noticed in diabetes mellitus. The insulin acts through receptors on the cell surface of adipocytes.
- These receptors are decreased, leading to insulin insensitivity in diabetes.
Adipose Tissue and Obesity
- The fat content of the adipose tissue can increase to unlimited amounts, depending on the amount of excess calories taken in. This leads to obesity.
- When fat droplets are overloaded, cell is destroyed, and TAG becomes extracellular. Such TAG cannot be metabolically reutilized and forms the dead bulk in obese individuals.
- Adipokines :- Are adipose derived hormones
- Leptin :- is a small peptide. The feeding behaviour is regulated by leptin. A defect in leptin or its receptor can lead to obesity.
- Adiponectin :– another polypeptide. Which increases the insulin sensitivity of muscle and liver.
Liver-Adipose Tissue Axis
- Liver produces fatty acid and TAG (triacylglycerol), which is transported as VLDL (very low density lipoprotein) in the blood.
- The fatty acids from VLDL are taken up by adipose tissue with the help of lipoprotein lipase, and stored as TAG.
- In adipose tissue this neutral fat is hydrolysed by hormone sensitive lipase into NEFA, which is carried by albumin in blood.
- The NEFA is utilized by the peripheral tissues, excess of which can be taken up by liver cells. Thus there is a constant flux of fat molecules from liver to adipose tissue and back.
Mobilization of triacylglycerols stored in adipose tissue.
- When low levels of glucose in the blood trigger the release of glucagon,
- The hormone binds its receptor in the adipocyte membrane and thus stimulates adenylyl cyclase, via a G protein, to produce cAMP.
- This activates PKA, which phosphorylates the hormone-sensitive lipase and perilipin molecules on the surface of the lipid droplet.
- Phosphorylation of perilipin permits hormonesensitive lipase access to the surface of the lipid droplet
- Where it hydrolyzes triacylglycerols to free fatty acids.
- Fatty acids leave the adipocyte, bind serum albumin in the blood, and are carried in the blood; they are released from the albumin and enter a myocyte via a specific fatty acid transporter.
- In the myocyte, fatty acids are oxidized to CO2, and the energy of oxidation is conserved in ATP, which fuels muscle contraction and other energy requiring metabolism in the myocyte.
Other Biochemistry Notes
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