Fat cell metabolism; a new way to treat diabetes and obesity

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(Last Updated On: April 4, 2020)
Adipose tissue
Adipose tissue. Image: BruceBlaus via Common Wikimedia

A new insight on fat cell metabolism has been discovered. Researchers from the University of California, San Deigo have studied the fat cells (adipocytes) from patients with diabetes and obesity on the molecular level and found something different. Adipose tissues which are also called fat cells are the main site for the regulation of carbohydrates and lipid homeostasis. They are mainly known for the carbohydrate and lipid metabolism, not for the amino acid metabolism.


However, these researchers have proven that the adipocytes can also utilize branched-chain amino acids (such as leucine and isoleucine) for the acetyl-CoA generation. For this purpose, researchers used isotope tracing to different preadipocytes and differentiated adipocytes to study the amount of their contribution to the different substrates to the TCA cycle (tricarboxylic acid, the central cyclic pathway of carbohydrate metabolism and lipogenesis).

Proliferating cells normally use glucose and glutamine to generate acetyl-CoA, however, differentiated adipocytes have shown to use a large amount of branched-chain amino acids such as isoleucine and leucine into the catabolic flux to generate acetyl-CoA constituting about 30 % of the acetyl-CoA for lipogenesis.

To confirm this, researchers grew adipocytes in medium with the cobalamine (an active component of the vitamin B12) deficiency that caused the accumulation of methylmalonic acid and led to the synthesis of odd-chain fatty acids. When vitamin B12 was supplemented into the medium, the synthesis of these metabolites was suppressed and the balance of the substrate entering the mitochondria was also altered.

Researchers also found that inhibition of the branched-chain amino acid catabolism led to decreased adipogenesis (differentiation of the adipocytes into the fat cells). All these results indicate a direct contribution of the branched-chain amino acids to the fat cell metabolism and a functional role of the branched-chain amino acids in adipocytes differentiation

This study has been published in the nature chemical biology (2015) with article doi: 10.1038/nchembio.1961

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