CNIC scientists discover how fat cells grow throughout the body

This process prevents tissue damage and protects the body from the consequences toxic accumulation of lipids in inappropriate places. The results, published in the journal Natural communicationsrepresent a significant advance in the understanding of metabolic diseases.

In addition, this discovery opens the door to the development of new therapeutic strategies to combat diseases linked to chronic energy excess, such as overweight, obesity, lipodystrophy and metabolic syndromeas well as its serious cardiovascular and metabolic complications.

In a society characterized by sedentary lifestyle and high-calorie dietsAdipose tissue plays a crucial role in metabolic health. Adipocytes have the ability to grow enormously to store energy in the form of fat, thereby preventing excess lipids from accumulating in organs such as the liver or the blood vessel walls -especially those of the heart and brain-, where it could cause irreversible damage.

However, this approach is not without risk. Too much fat can cause degradation of adipocytesreleasing his toxic content and generate inflammation and metabolic alterations. The CNIC study focuses on how adipocytes adapt to resist mechanical stress derived from its expansion to accommodate accumulated fat.

The team analyzed the role of caveolaesmall invaginations of the cell membrane which act as sensors and shock absorbers of these tensions. “When the adipocyte accumulates fat and its surface is subjected to greater tension, the caveolae flatten, releasing a ‘reservoir’ of membrane that allows the cell to grow without rupturing. When fat reserves fat decreases, these structures come together to reduce excess membrane and restore cell stability,” explains. Maria Aboy Pardalfirst author of the research.

Caveolae: more than a structural support

In addition to physically protecting adipocytes, caveolae play an essential role in coordinating cellular metabolism. During the expansion process, explains Del Pozo, “the molecular components of these structures move to other compartments of the cell, send signals which adjust metabolic activity to the level of energy reserves. “This capacity makes caveolae key elements in the efficient functioning of adipocytes.”

However, when these structures are lacking or do not function properly, adipocytes become more rigid, vulnerable to breakage and less efficient in the accumulation of energy. As a result, adds Aboy Pardal, “this generates inflammation and the metabolic health of the body is compromised. This phenomenon is linked to diseases such as lipodystrophy, a condition in which patients are unable to form fatty depositswhich leads to serious metabolic and cardiovascular alterations.

Likewise, the CNIC study highlights the role of a key protein, Caveolin-1 (Cav1), undergoing reorganization of caveolae. This protein must be phosphorylated (chemically modified) in a specific amino acid to allow caveolae to flatten appropriately in response to fluctuations in mechanical stress in the cell membrane.

The researchers developed a transgenic mouse expressing a modified form of Cav1 incapable of being phosphorylated. In this mouse, that is to say when Cav1 phosphorylation does not occur, fat cells cannot grow properly to the tension exerted by the accumulation of fat, which negatively impacts its ability to store energy and maintain the integrity of the cell.

The failure of this very basic mechanism ultimately leads to lipodystrophy and its serious consequences. Del Pozo concludes that “these results allow us to better understand how adipose tissue responds to mechanical forces associated with excess energy. In a context of obesity and metabolic syndrome, this protective mechanism is key for minimize damage to the body“.

The research benefited from the collaboration of the transgenesis, pluripotent cell technology, microscopy and histopathology units of the CNIC. In addition, researchers from the Madrid Institute of Materials Science (ICMM, CSIC) collaborated; CIMUS Research Center for Molecular Medicine and Chronic Diseases; CNIO; “Sols-Morreale” Biomedical Research Institute; and Margarita Salas Biological Research Center –CSIC.