MCQ1
Increased lipolysis of fat stores, which can result from starvation, diabetes
mellitus, or corticosteroid use, is most likely to cause steatosis (fatty
liver) through which one of the listed mechanisms?
a. Decreased free fatty acid excretion from the liver leads to free fatty acid accumulation
in hepatocytes
b. Excess NADH (high NADH/NAD ratio) causes excess production of lactate
from pyruvate, which accumulates in hepatocytes
c. Increased free fatty acid delivery to the liver leads to triglyceride accumulation
in hepatocytes
d. Inhibition of apoprotein synthesis by the liver leads to phospholipid accumulation
in hepatocytes
e. Inhibition of HMG-CoA reductase activity leads to cholesterol accumulation in
hepatocytes
Answer The answer is c. (Cotran, pp 39–40, 859. Chandrasoma, 3/e, pp 8–10.)
Free fatty acids are normally taken up by the liver and esterified to triglyceride,
converted to cholesterol, oxidized into ketone bodies, or incorporated
into phospholipids that can be excreted from the liver as very-low-density
lipoproteins (VLDLs). Abnormalities involving any of these normal metabolic
pathways may lead to the accumulation of triglycerides within the
hepatocytes. This accumulation of triglycerides is called fatty change or
steatosis. Examples of abnormalities that produce hepatic steatosis include
diseases that cause excess delivery of free fatty acids to the liver or diseases
that cause impaired lipoprotein synthesis. Excess delivery of free fatty acids
occurs in conditions that increase lipolysis of adipose tissue, such as starvation,
diabetes mellitus, and corticosteroid use. Increased formation of
triglycerides can result from alcohol use, as alcohol causes excess NADH
formation (high NADH/NAD ratio), increases fatty acid synthesis, and
decreases fatty acid oxidation. Impaired apoprotein synthesis occurs with
carbon tetrachloride poisoning, phosphorous poisoning, and protein malnutrition.
Inhibition of HMG-CoA reductase activity is the mechanism of
lovastatin, which indirectly increases liver LDL receptors and increases LDL
clearance from the blood.
