Lipogenesis

Lipogenesis Definition

Lipogenesis is the process of producing lipid or fat to store biochemical energy for later metabolic use. It is a biochemical process where, for instance, acetyl-CoA is converted to triglyceride. The excess energy that will not be used immediately can be stored in the form of fats. The energy from acetyl-CoA is stored in fat biomolecules. Lipogenesis includes (1) fatty acid synthesis and (2) triglyceride synthesis. Fatty acid synthesis occurs in the cytoplasm and is characterized by the repeated addition of two-carbon units to acetyl-CoA. In triglyceride synthesis, three fatty acids are esterified to glycerol in the endoplasmic reticulum. The cells that carry out lipogenesis are mostly adipocytes and liver cells.

Lipogenesis is associated with various metabolic pathways, such as glucose uptake and cholesterol synthesis. It plays a pivotal role in developing metabolic disorders such as obesity, hepatic lipid accumulation, hepatic steatosis, diabetes mellitus, and nonalcoholic fatty liver disease (NAFLD). It may also have an effect on the expression of genes related to insulin sensitivity and glucose intolerance.

• Lipogenesis vs. Lipolysis

While lipogenesis is the biological process of producing or synthesizing fatty acids from simpler precursors, lipolysis is the breaking down stored fats into their constituent components, such as fatty acids and glycerol. Fatty acids are vital in living organisms as they are essential to the plasma membrane. They are also an important energy source when stored as triglycerides. Both lipogenesis and lipolysis are central to maintaining metabolic homeostasis. Below is the table summarizing the difference between lipogenesis and lipolysis.

Table 1: Lipogenesis vs. Lipolysis
Features	Lipogenesis	Lipolysis
Definition	The process of synthesizing or creating new fat molecules from simpler precursors (lipid biosynthesis)	The process of breaking down stored fat (fatty acid oxidation), specifically triglycerides
Function	For the storage of excess energy in the form of triglycerides	Releases energy for use by the body
Location	Lipogenesis occurs in tissues like the liver and adipose tissue. The liver is particularly involved in de novo fatty acid synthesis, while adipose tissue stores excess fat. In triglyceride synthesis, three fatty acids are esterified to glycerol in the endoplasmic reticulum.	Lipolysis primarily occurs in adipose tissue but can also take place in other tissues where stored fat needs to be mobilized for energy. Fatty acid oxidation occurs primarily in the mitochondria of cells.
Hormonal Regulation	Hormones like insulin play a stimulatory role in lipogenesis. High insulin levels, often associated with elevated blood glucose, promote the synthesis of fatty acids.	Hormones such as epinephrine and norepinephrine, which are released in response to low blood glucose or during periods of increased energy demand, stimulate lipolysis. Lipolysis is activated when the circulating insulin level is low whereas the circulating epinephrine is high.
Substrates	Substrates are acetyl-CoA, glucose, and amino acids. These are precursors used to create new fat molecules.	The substrates for lipolysis are triglycerides, which are composed of glycerol and fatty acids.
Energy Balance	Lipogenesis contributes to energy storage and can lead to weight gain and the accumulation of body fat when it is in excess. It plays a role in maintaining energy balance.	Lipolysis is a process of energy expenditure. It helps to utilize stored fat for energy, contributing to weight loss and a reduction in body fat when energy expenditure exceeds intake.

 

Fatty Acid Metabolism and Synthesis (Lipogenesis) by Wondersofchemistry:

Biochemical Pathways Of Lipogenesis

Biochemical pathways that comprise lipogenesis are as follows:

1. De novo fatty acid synthesis. The process primarily occurring in the liver and adipose tissue, is a multi-step process involving enzymes like fatty acid synthase (FAS). It begins with the conversion of acetyl-CoA into fatty acids.
2. Triglyceride formation. This is essential for storing excess calories (e.g., from excessively high carbohydrate or high-fat diet) in the form of fat. The fatty acids are esterified with glycerol, resulting in the formation of triglycerides. These molecules are stored in adipose tissues and can be mobilized when the body requires additional energy, serving a crucial role in maintaining metabolic homeostasis.

Regulation Of Lipogenesis

The intricate regulation of lipogenesis involves both hormonal control and enzymatic processes.

• Key enzymes of lipogenesis

Two enzymes are vital for the process of lipogenesis. These are fatty acid synthase (catalyzes a series of reactions that convert acetyl-CoA into long-chain fatty acids) and acetyl-CoA carboxylase (catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA).

• Insulin stimulation of lipogenesis

Insulin level rises when the pancreas releases insulin into the bloodstream. High glucose level (e.g. from dietary sources) promotes the release of insulin from the pancreas. In the presence of high insulin levels, lipogenesis predominates over lipolysis. Insulin induces a cascade of reactions that lead to the reduction of cAMP level. While insulin slows down lipolysis, it induces lipogenesis. This ensures that lipolysis and lipogenesis do not occur at the same time. When insulin is released by the pancreas to the bloodstream, the level of insulin increases. This results in the slowing down of lipolysis by inducing a series of reactions that reduce cAMP level and lower sympathetic nervous outflow. Insulin also stimulates pyruvate dehydrogenase phosphatase that removes phosphate from pyruvate dehydrogenase, thereby activating the latter to convert pyruvate to acetyl-CoA. The acetyl-CoA is carboxylated to form malonyl-CoA through the action of acetyl-CoA carboxylase. The malonyl-CoA plays a role in the chain elongation in fatty acid biosynthesis. The liver cells, though, release triglycerides in the form of very-low-density lipoproteins (VLDL) into the bloodstream.

• Growth hormone regulation of lipogenesis

Growth hormone inhibits lipogenesis by interfering with the expression and activity of key enzymes for lipogenesis, such as fatty acid synthase (FAS) and acetyl-CoA carboxylase. It also reduces insulin sensitivity, especially in the liver and the adipose tissue, while stimulating lipolysis. By increasing lipolysis, GH mobilizes stored triglycerides for energy utilization, thereby opposing the energy storage role of lipogenesis.

Human Lipogenesis

In humans, lipogenesis occurs primarily in the liver and adipose tissues:

• Hepatic lipogenesis. This process is central to hepatic lipid metabolism and maintaining lipid homeostasis. It contributes to the synthesis of cholesterol and, thus, to cholesterol metabolism.
• Adipose tissue lipogenesis. Adipose tissues specialize in the storage of triglycerides, playing a vital role in regulating lipid balance and energy storage. Excess fat accumulation can lead to conditions like insulin resistance and obesity.

Excessive lipogenesis contributes to the accumulation of adipose tissue, resulting in obesity. It can also lead to certain metabolic disorders, such as hepatic insulin resistance and type 2 diabetes. They are closely linked to imbalances in lipogenesis. The relationship between lipogenesis and insulin sensitivity offers new strategies to address these metabolic conditions.

References

1. Smith, J. R., & Chalk, D. (2018). Lipogenesis: New Perspectives and Emerging Mechanisms. Wiley.
2. Brown, L. M., & Osada, T. (2019). Regulation of Lipogenesis in Adipose Tissues. Annual Review of Nutrition, 39, 1-27.
3. Classic Reference 1: Ahrens, E. H., Jr., & Insull, W. (1966). The Fatty Acid Composition of the Plasma Lipids and Lipogenesis in Man. The Journal of Clinical Investigation, 45(11), 1813-1825.
4. Classic Reference 2: Randle, P. J., & Kerbey, A. L. (1979). Lipogenesis from glucose in human adipose tissue. Annals of Nutrition and Metabolism, 23(2), 85-94.

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