An 18-year-old female is diagnosed as obese. She maintains a sedentary life style and eats a high-fat, high-sugar diet. Maintenance of this diet and lifestyle has led to lipogenesis and obesity. Which of the following best explains carbohydrates induced obesity?
A) Excess glycerol is obtained through glycolysis
B) Fatty acids are excessively synthesized from Acetyl co A
C) NADPH is excessively obtained through HMP pathway
D) Triglycerides are excessively synthesized
E) All of the above.
The correct answer is E- All of the above. Excess carbohydrate ingestion is a major cause of obesity. Obesity is a state of excess adipose tissue mass. Adipose tissue is composed of the lipid-storing adipose cell and a stromal/vascular compartment in which cells including preadipocytes and macrophages reside. Adipose mass increases by enlargement of adipose cells through lipid deposition, as well as by an increase in the number of adipocytes. The predominant lipid in the adipose cells is triglyceride. Triglyceride contains a glycerol backbone and three fatty acids. Carbohydrates increase the triglyceride load by the following mechanisms:
Glucose is the principal representative of carbohydrates. The metabolism of glucose provides all the substances required for the synthesis of triglycerides, for example,
a) Glycerol- Glycerol is obtained through glycolysis (figure-1). Dihydroxyacetone-P (produced by the cleavage of Fructose 1, 6 bisphosphate) is converted to glycerol-3-P by the action of Glycerol-3-P dehydrogenase. Glycerol-3-P or active glycerol is used for the synthesis of Triglyceride (figure-1).
b) Fatty acids- Acetyl co A, the precursor of fatty acids is obtained from Pyruvate, the end product of glycolysis (Acetyl co A can also be obtained through alternative sources).
c) NADPH- HMP pathway, the alternative pathway of glucose utilization provides NADPH, for this reductive pathway of fatty acid biosynthesis.
d) Role of insulin- Insulin released as a result of excess plasma glucose load, activates Acetyl co A carboxylase, the rate limiting enzyme of fatty acid biosynthesis. Insulin also promotes glucose uptake through GLUT-4 receptors, and hence provides precursors for fatty acid synthesis and activates Lipoprotein lipase, providing more fatty acids, obtained through degradation of lipoproteins for esterification with glycerol.
Figure-1- Summary of glucose induced obesity
Excess fructose and sucrose intake is also responsible for increased triglyceride levels and obesity. Fructose undergoes more rapid glycolysis in the liver than does glucose, because it bypasses the regulatory step catalyzed by phosphofructokinase (Figure-2). This allows fructose to flood the pathways in the liver. High fructose consumption can lead to excess pyruvate production, causing a buildup of Krebs cycle intermediates. Accumulated citrate can be transported from the mitochondria into the cytosol of hepatocytes, converted to acetyl CoA by citrate lyase and directed toward fatty acid synthesis. Additionally, DHAP can be converted to glycerol 3-phosphate as previously mentioned, providing the glycerol backbone for the triglyceride molecule. Triglycerides are incorporated into very low density lipoproteins (VLDL), which are released from the liver destined toward peripheral tissues for storage in both fat and muscle cells.
Figure-2- Summary of carbohydrate induced obesity.
Since all the above mentioned mechanisms are involved in lipogenesis, induced by excess carbohydrates intake,thus E- is the correct option.
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