- Fatty liver refers to the deposition of excess triglycerides in the liver cells. The normal concentration of lipids in liver is around 5%. Liver is not storage organ for fat. In the normal liver, Kupffer cells contain lipids in the form of droplets.
- In fatty liver, droplets of triacylglycerols are found in the entire cytoplasm of hepatic cells. Causes impairment in metabolic functions of liver. Fatty liver is associated with fibrotic changes & cirrhosis.
- Causes of fat deposition in liver: Mobilization of NEFA from adipose tissue. Excess synthesis of fatty acid from glucose. Reduced removal of fat from liver: Toxic injury to liver. Secretion of VLDL needs synthesis of apo B-100 & apo C. Decreased oxidation of fat by hepatic cells.
- The capacity of liver to take up the fatty acids from blood, exceeds its capacity for excretion as VLDL. This leads to the overproduction of triacylglycerols & their accumulation in liver. Fatty liver can occur in diabetes mellitus & starvation due to increased lipolysis in adipose tissue.
- Alcoholism & high fat diet are associated with increased mobilization of fatty acids & cause fatty liver. Alcohol also inhibits fatty acid oxidation & promotes fat synthesis & its deposition. Excess calorie intake: Excess calories, either carbohydrates or as fats, are deposited as fat. Obesity may be accompanied by fatty liver.
- In toxic injury to the liver due to poisoning by compounds like carbon tetrachloride, arsenic, lead, etc. Inhibit protein synthesis & causes fatty liver. lmpaired synthesis of lipoproteins: The synthesis of very low density lipoproteins (VLDL) actively takes place in liver.
- VLDL formation requires phospholipids & apoprotein B. Impaired lipoprotein synthesis may be due to: Defect in phospholipid synthesis. A block in apoprotein formation. A failure in the formation/secretion of lipoprotein. Fatty liver due to impairment in phospholipid synthesis is studied in detail.
- Dietary deficiency of lipotropic factors such as choline, betaine, inositol etc. Deficiency of essential fatty acids leads to a decreased formation of phospholipids. Lipoprotein synthesis & their secretion require ATP. Decrease in the availability of ATP.
- Pyridoxine & pantothenic acid deficiency also impairs lipoprotein formation. Deficiency of vitamin E is associated with fatty liver. Selenium acts as a protective in nature. Certain hormones like ACTH, insulin, thyroid hormones, adrenocorticoids promote deposition of fat in liver.
- NAFLD is the most common liver disease, where fat is accumulated in hepatocytes. High fat diet & uncontrolled diabetes mellitus are the most common causes. As the disease progresses, inflammatory reaction occurs, which is termed as NASH.
- Fat molecules infiltrate the cytoplasm of the cell (fatty infiltration). These are seen as fat droplets in the cytoplasm The nucleus is pushed to a side of the cell. Ultimately the hepatic cell is lysed. As a healing process, fibrous tissue is laid down, causing fibrosis of liver or cirrhosis.
- These are the substances required for the normal mobilisation of fat from liver. The deficiency of these factors may result in fatty liver. Important lipotropic factors: Choline, Betaine, Methionine & Inositol. Folic acid, vitamin B12, glycine & serine also serve as lipotropic factors.
- Choline & inositol are components of phospholipids & required for their synthesis. The other lipotropic factors are concerned with transmethylation reactions & ultimately, the synthesis of choline. Severe protein deficiency (e.g. kwashiorkor) causes fatty liver.
- Due to a defect in the synthesis of choline as a result of insufficient amino acid (methionine) supply. Vitamin E & selenium give protection due to their anti-oxidant effect. Omega 3 fatty acids have a protective effect against fatty liver.
- Decreased phospholipid synthesis. Impaired formation of lipoprotein membrane. Reduced synthesis of carnitine due to insufficient supply of methyl groups. Impairment in fatty acid oxidation.
Textbook of Biochemistry-U Satyanarayana
Textbook of Biochemistry-DM Vasudevan.